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- ArticleAçık Erişim2026ATP attenuates olaparib-induced gastric damage in rats
Fakirullahoglu, Mesud; Temiz, Ayetullah; Yeni, Mustafa; Sezgin, Esra Tuba; Yazici, Gulce Naz; Altuner, Durdu; Gulaboglu, Mine; Suleyman, Halis
Background Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor widely used in cancer therapy, has been associated with gastrointestinal adverse effects; however, the underlying mechanisms remain unclear. Previous studies have suggested that oxidative stress may contribute to olaparib-induced tissue injury.Objective This study aimed to investigate the protective effects of adenosine triphosphate (ATP) against olaparib-induced gastric damage in rats.Methods Animals were divided into healthy control (HG), olaparib alone (OLPG), ATP alone (ATPG), and ATP + olaparib (ATOLG) groups. Gastric injury was evaluated by macroscopic assessment of ulcer area and ulcer number. Histopathological alterations were examined using hematoxylin-eosin (H&E) staining, and oxidative stress status was assessed by measuring lipid peroxidation and antioxidant defense parameters.Results Olaparib administration induced marked gastric mucosal injury, characterized by increased ulcer area and ulcer number, severe histopathological damage, and pronounced oxidative stress. In contrast, ATP co-administration significantly attenuated gastric injury, as evidenced by reduced ulcer area and ulcer number, improved histopathological architecture, and restoration of oxidative balance. Compared with the OLPG group, the ATOLG group showed significant improvement in macroscopic, histopathological, and oxidative stress parameters.Conclusion ATP administration attenuated olaparib-induced gastric damage and improved oxidative stress parameters in rats. Although the underlying mechanisms were not directly investigated in the present study, the obtained findings provide preliminary experimental evidence suggesting that ATP may have protective potential against olaparib-induced gastric injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Potential Hepatoprotective Effects of Adenosine Triphosphate Against Olaparib-Induced Oxidative Liver Injury: An Experimental Rat Model
Baykan, Ahmed Ramiz; Cerrah, Serkan; Kartal Baykan, Emine; Tanas, Serdar; Yavuzer, Bulent; Yazici, Gulce Naz; Kuzucu, Mehmet; Altuner, Durdu; Suleyman, Halis
Background: Olaparib, a clinically established poly (ADP-ribose) polymerase (PARP) inhibitor widely used in oncology, has significantly improved outcomes in several malignancies. However, increasing evidence indicates that olaparib may induce hepatocellular injury through mechanisms involving oxidative stress, inflammation, and mitochondrial dysfunction. Adenosine triphosphate (ATP), a key regulator of cellular bioenergetics and redox homeostasis, may confer protection against oxidative tissue injury. This study investigated the hepatoprotective effects of ATP against olaparib-induced oxidative liver damage in rats and compared its efficacy with melatonin. Methods: Twenty-four male albino Wistar rats were randomly assigned to four experimental groups (n = 6): healthy control (HG), olaparib-treated (OLP), ATP plus olaparib (ATOL), and melatonin plus olaparib (MLOL). Olaparib was administered at a dose of 100 mg/kg orally twice daily, whereas ATP (5 mg/kg, intraperitoneally) and melatonin (10 mg/kg, orally) were administered once daily. The treatments were administered for 14 consecutive days. Hepatic oxidative and inflammatory status was assessed by measuring malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-6 (IL-6) and ATP levels in liver tissue. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured as biochemical indicators of hepatocellular injury. Liver tissues were also examined histopathologically. Results: Olaparib administration significantly increased hepatic MDA and IL-6 levels together with serum ALT and AST activities, while significantly reducing hepatic tGSH and ATP levels and SOD and CAT activities compared with the healthy group (p < 0.001). Both ATP and melatonin significantly attenuated these alterations (p < 0.001). Notably, ATP demonstrated a more pronounced protective effect than melatonin, particularly in suppressing aminotransferase elevations and improving histopathological liver architecture. Conclusion: ATP significantly alleviates olaparib-induced hepatotoxicity by attenuating oxidative stress, suppressing inflammatory responses, restoring antioxidant defense mechanisms and significantly replenishing depleted hepatic ATP levels. These findings suggest that ATP may represent a promising therapeutic strategy for preventing PARP inhibitor-associated drug-induced liver injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Protective effects of adenosine triphosphate, thiamin, thiamin pyrophosphate, and their combination against linezolid-induced renal injury and lactic acidosis in rats
Admis, Ozlem; Yavuzer, Bulent; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Mendil, Ali Sefa; Yucel, Nurinisa; Suleyman, Halis
Linezolid, an oxazolidinone antibiotic effective against Gram-positive pathogens, may cause nephrotoxicity and lactic acidosis during prolonged therapy. This experimental study investigated the protective effects of adenosine triphosphate (ATP), thiamin, thiamin pyrophosphate (TPP), and their combination (ATTP) on linezolid-induced renal injury and lactic acidosis in rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6): healthy control (HG), linezolid only (LZD), ATP+linezolid (ATLZD), thiamin + linezolid (TLZD), TPP+linezolid (TPLZD), and ATP+thiamin + TPP+linezolid (ATTPL). Linezolid (125 mg/kg, orally) was administered twice daily, while ATP (4 mg/kg), thiamin (20 mg/kg), and TPP (20 mg/kg) were given intraperitoneally once daily for 28 days. At the end of treatment, kidney tissues were examined for oxidative stress markers [malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)] and histopathology, and blood samples were analyzed for blood urea nitrogen (BUN), creatinine, and lactate. Linezolid increased oxidative stress, suppressed antioxidants, and elevated BUN, creatinine, and lactate levels. ATP partially improved the oxidative balance in renal tissue but failed to prevent hyperlactatemia and impaired renal function. Thiamin did not produce significant changes. TPP markedly improved oxidative stress markers and reduced renal dysfunction. The triple combination provided the most pronounced protection, restoring antioxidant defenses, kidney function, and lactate levels to near-control values. Histopathological evaluation revealed marked tubular degeneration, interstitial hemorrhage, and mononuclear cell infiltration in the linezolid group, which were markedly improved by TPP and combination therapy. These findings indicate that TPP protects against linezolid-induced nephrotoxicity and lactic acidosis, with its efficacy further enhanced by ATP.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Effects of adenosine triphosphate and reduced glutathione on biochemical, histopathological and immunofluorescence alterations associated with atezolizumab-induced cardiac tissue injury
Yasar, Yesim Kaya; Sezgin, Esra Tuba; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Coban, Taha Abdulkadir; Suleyman, Halis
Background – In this study, the potential protective effects of adenosine triphosphate (ATP) and glutathione (GSH) against atezolizumab-induced cardiac injury in rat heart tissue were investigated. Methods – A total of 24 male albino Wistar rats were used in the experiment. The animals were divided into four groups: healthy group adenosine triphosphate + atezolizumab (ATAZ), GSH + atezolizumab (GHAZ), and atezolizumab alone (ATZ). ATP was administered intraperitoneally at a dose of 4 mg/kg, while GSH was administered orally at a dose of 200 mg/kg for 7 days. Atezolizumab was administered intraperitoneally to the experimental groups at a dose of 10 mg/kg twice weekly. At the end of the experiment, malondialdehyde total glutathione (tGSH), superoxide dismutase catalase, interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in heart tissues were measured using biochemical methods. In addition, histopathological and immunofluorescence examinations were performed. Results – The results showed that oxidative stress and inflammation markers increased, whereas antioxidant parameters decreased in the atezolizumab-treated group. ATP and GSH administration significantly attenuated these changes and exerted protective effects on cardiac tissue. Conclusion – Overall, ATP and GSH ameliorated the biochemical, histopathological, and immunofluorescence changes associated with atezolizumab-induced cardiac injury in this experimental model.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Pathophysiology of sildenafil-induced ocular toxicity in rats and treatment
Cicek, Ibrahim; Caliskan, Busra; Yavuzer, Bulent; Altuner, Durdu; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Karatas, Ezgi; Suleyman, Halis
RESULTS: Sildenafil increased oxidant (malondialdehyde) levels and decreased antioxidant levels (total glutathione, superoxide dismutase, catalase) in rat ocular tissues and caused severe oxidative stress. In addition, sildenafil has been shown histopathologically to cause oxidative damage in retinal layers. ATP treatment suppressed oxidative stress and attenuated histopathological damage in the retinal layers. CONCLUSION: ATP protects retinal tissue against sildenafil-induced ocular oxidative damage in rats and may contribute to the development of novel approaches to prevent or treat this damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Mitigating Hydroxychloroquine-Induced Oxidative Liver Damage: The Roles of Adenosine Triphosphate, Liv-52, and Their Combination in Rats
Kandefer, Meryem Yalvac; Sezgin, Esra Tuba; Suleyman, Bahadir; Cimen, Ferda Keskin; Memiş, Fulya; Gulaboglu, Mine; Suleyman, Halis
Hydroxychloroquine (HCQ), originally developed as an antimalarial agent, has been associated with hepatotoxic effects in experimental and clinical settings. Our study was designed to evaluate the effects of this agent on liver toxicity and to understand the protective roles of adenosine triphosphate (ATP), Liver-52 (Liv-52), and their combination. Male Wistar rats (250–280 g) were randomly assigned to five groups (n = 6): healthy control (C), HCQ only (H), ATP plus HCQ (AH), Liv-52 plus HCQ (LH), and ATP–Liv-52 plus HCQ (ALH). ATP (4 mg/kg) was administered intraperitoneally once daily, whereas Liv-52 (20 mg/kg) was administered orally via gavage. One hour later, all groups except C received HCQ (120 mg/kg, orally, twice daily). All treatments were continued for seven consecutive days. At the end of the experiment, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and liver tissues were analyzed for malondialdehyde (MDA), total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities, along with histopathological evaluation. HCQ administration significantly increased oxidative stress, as evidenced by elevated MDA levels (p < 0.01) and reduced antioxidant parameters, including GSH, SOD, and CAT (p < 0.05), accompanied by prominent histopathological damage. Treatment with ATP or Liv-52 markedly ameliorated these alterations by decreasing MDA and restoring antioxidant markers. The combination treatment was observed to exhibit the most pronounced protective effect; it significantly reduced MDA levels, improved GSH, SOD, and CAT levels more effectively, and produced significant decreases in AST and ALT values (p < 0.05).
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Comparative Protective Effects of ATP and TPP Against Olaparib-Induced Ovarian Injury in Rats: Insights from Biochemical Parameters, Histopathology, and IRE1α, Cleaved Caspase-3, LC3B, and NF-κB p65 Double Immunofluorescence
Paltaci, Seyma Ilayda; Yilmaz, Nesrin; Kozali Uzun, Sukran; Yavuzer, Bulent; Coban, Taha Abdulkadir; Ozkaraca, Mustafa; Gungor, Ali; Yaqubov, Kamandar; Suleyman, Halis
Background: Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor used to treat several malignancies. Previous studies have reported that olaparib may induce ovarian injury by elevating reactive oxygen species and impairing cellular energy homeostasis. ATP is a central regulator of intracellular energy balance and antioxidant defense, whereas thiamine pyrophosphate (TPP), the active form of vitamin B1, supports ATP biosynthesis and possesses antioxidant and anti-inflammatory properties. This study compared the protective effects of ATP and TPP against olaparib-induced ovarian injury in rats. Methods: Twenty-four female Wistar albino rats were randomly assigned to four groups (n=6 each): healthy control (HG), olaparib-only (OLP), ATP plus olaparib (ATOL), and TPP plus olaparib (TPOL). Olaparib (100 mg/kg, orally, twice daily), ATP (5 mg/kg, intraperitoneally, once daily), and TPP (25 mg/kg, intraperitoneally, once daily) were administered for 14 consecutive days. Ovarian tissue levels of oxidant (MDA), antioxidants (tGSH, SOD, CAT), and pro-inflammatory cytokine (IL-6) were determined. Tissue specimens underwent histopathological (follicular and parenchymal degeneration) and double immunofluorescence analyses (IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity). Results: Olaparib significantly increased oxidant and pro-inflammatory cytokine levels and decreased antioxidant levels. Histopathology revealed severe follicular and parenchymal degeneration, and immunofluorescence analysis showed significantly increased IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity. Both ATP and TPP pre-treatment significantly attenuated olaparib-induced oxidative stress, inflammatory responses, histopathological injury, and cellular stress marker immunopositivity. ATP demonstrated a more pronounced protective effect than TPP, particularly regarding follicular degeneration suppression and LC3B and NF-κB p65 immunopositivity. Conclusion: Olaparib induced ovarian injury accompanied by oxidative stress, cytokine-mediated inflammation, IRE1α-related endoplasmic reticulum stress, cleaved Caspase-3-related apoptosis, LC3B-related autophagy, and NF-κB-related inflammatory signaling. Both ATP and TPP attenuated olaparib-associated injury, with greater effects for ATP. These findings suggest that maintenance of cellular energy homeostasis may represent a promising strategy for attenuating PARP inhibitor-induced ovarian injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Liv-52 Attenuates Erlotinib-Induced Liver Injury via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats
Bulut, Seval; Altuner, Durdu; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Kuzucu, Mehmet; Hendem, Engin; Suleyman, Halis
Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is widely used in cancer therapy; however, hepatotoxicity limits its clinical use. This study investigated the protective effects of Liv-52, a polyherbal hepatoprotective formulation, against erlotinib-induced hepatotoxicity in rats and compared its efficacy with melatonin. The animals (n = 24, Wistar albino rats) were randomly categorized into four groups: healthy (HG), erlotinib (ERG), Liv-52 + erlotinib (LEG), and melatonin + erlotinib (MEG). Liv-52 (50 mg/kg/day, orally) and melatonin (10 mg/kg/day, orally) were administered once daily for two weeks. Erlotinib (10 mg/kg, orally) was given every other day to ERG, LEG, and MEG groups for two weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured. Hepatic malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed. Additionally, double immunofluorescence staining was performed to evaluate apoptotic (poly[ADP-ribose] polymerase-1 [PARP-1], apoptosis-inducing factor [AIF]), inflammatory (cyclooxygenase-2 [COX-2]), and anti-inflammatory (interleukin-10 [IL-10]) biomarkers in liver tissues. Histopathological examination was also conducted to assess structural alterations. Erlotinib significantly increased MDA, ALT, AST, and LDH while decreasing tGSH, SOD, and CAT (p < 0.001). Strong immunoreactivity for PARP-1, AIF, IL-10, and COX-2, as well as severe hydropic degeneration and necrosis, was observed in ERG (p < 0.05). Both Liv-52 and melatonin significantly ameliorated biochemical, histopathological, apoptotic, and inflammatory alterations (p < 0.05). Notably, Liv-52 demonstrated superior hepatoprotective efficacy compared to melatonin. These findings indicate that Liv-52 effectively attenuates erlotinib-induced hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, thereby preserving liver function and structural integrity.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Targeting Oxidative Stress and Inflammation in Pembrolizumab-Induced Renal Injury: A Comparative Evaluation of the Protective Effects of Flunarizine and Carvacrol in Rats
Hendem, Engin; Yavuzer, Bulent; Sezgin, Esra Tuba; Gunay, Murat; Ozkaraca, Mustafa; Gungor, Ali; Altuner, Durdu; Suleyman, Halis
Background: Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is widely employed in oncological practice; however, its propensity to induce nephrotoxicity through immune-mediated oxidative and inflammatory mechanisms remains an insufficiently characterized clinical concern. The present study comparatively investigated the renoprotective effects of flunarizine, a voltage-dependent calcium channel antagonist, and carvacrol, a monoterpene, against pembrolizumab-induced renal injury in rats. Methods: Twenty-four male Wistar albino rats were assigned to four groups (n = 6): healthy control (HG), pembrolizumab alone (PZB), flunarizine+pembrolizumab (FLPZ), and carvacrol+pembrolizumab (CCPZ). Pembrolizumab was administered intraperitoneally at 5 mg/kg; flunarizine orally at 5 mg/kg and carvacrol intraperitoneally at 50 mg/kg, once daily for seven consecutive days. Renal oxidative status was assessed by measuring malondialdehyde (MDA) and total glutathione (tGSH) levels. Histopathological evaluation was performed using hematoxylin and eosin staining. Two double immunofluorescence panels were employed to assess 3,3′-dityrosine/Hepatitis A virus cellular receptor 1 (HAVCR1) and cyclooxygenase-1 (COX-1)/cyclooxygenase-2 (COX-2) expression, respectively. Results: Pembrolizumab caused pronounced oxidative stress and inflammatory responses in renal tissue, leading to a significant increase in renal MDA levels and a marked decrease in tGSH levels. These biochemical alterations were accompanied by severe tubular degeneration and increased expression of 3,3′-dityrosine, which is associated with oxidative damage, as well as HAVCR1, a marker of cellular injury, and COX-1 and COX-2, which reflect inflammatory activity. These findings indicate that pembrolizumab disrupts the renal redox balance and activates both oxidative and inflammatory pathways in kidney tissue. Flunarizine and carvacrol significantly reduced these pathological changes. Both agents attenuated oxidative stress markers and supported antioxidant defenses, thereby alleviating tissue damage. However, flunarizine demonstrated a more pronounced renoprotective effect across all evaluated parameters, restoring MDA and tGSH levels closer to physiological values and reducing tubular injury to a minimal level. Carvacrol showed a more limited but still statistically significant protective effect. Conclusions: Both agents confer significant renoprotection against pembrolizumab-induced oxidative injury; however, flunarizine exhibits a more robust protective profile, likely attributable to its capacity to attenuate calcium-mediated mitochondrial dysfunction and preserve cellular bioenergetic homeostasis.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Protective Role of Adenosine Triphosphate Against Tamoxifen-Induced Retinal Toxicity in a Rat Model
Karatas, Ezgi; Yavuzer, Bulent; Koksaldi, Seher; Kayabasi, Mustafa; Sezgin, Esra Tuba; Sarigul, Cengiz; Demir, Ozlem; Suleyman, Bahadir; Suleyman, Halis
Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Investigation of the Protective Effect of Centella asiatica Against Doxorubicin-Induced Testicular Damage in Rats
Bedir, Fevzi; Suleyman, Zeynep; Kocaturk, Huseyin; Altay, Mehmet Sefa; Keskin Cimen, Ferda; Altuner, Durdu; Babayeva, Mansura; Suleyman, Halis
Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Effects of ATP and Taxifolin on Atezolizumab-Induced Renal Injury: A Biochemical, Histopathological, and Immunofluorescence Evaluation
Kilic, Adil Furkan; Sezgin, Esra Tuba; Huseynova, Gulbaniz; Sarigul, Cengiz; Ozkaraca, Mustafa; Gungor, Ali; Mammadov, Renad; Suleyman, Halis; Cimen, Orhan
Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to investigate and comparatively evaluate the protective effects of adenosine triphosphate (ATP) and taxifolin against atezolizumab-induced renal tissue injury in rats. Methods: Animals were divided into four groups: healthy (HG), atezolizumab (ATZ), ATP + atezolizumab (ATAZ), and taxifolin + atezolizumab (TXAZ). ATP (4 mg/kg, i.p.) and taxifolin (50 mg/kg, oral) were administered for six days, while atezolizumab (10 mg/kg, i.p.) was given on days 1 and 4. On day 7, renal tissues were collected for biochemical, histopathological, and double immunofluorescence analyses. Results: Atezolizumab significantly increased malondialdehyde (MDA) levels and decreased total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels, indicating enhanced oxidative stress and impaired antioxidant defense. These changes were accompanied by tubular degeneration and increased expression of apoptotic markers. Both ATP and taxifolin significantly ameliorated these alterations; however, ATP demonstrated a more pronounced protective effect. Conclusions: In conclusion, ATP and taxifolin attenuated the biochemical, histopathological, and immunofluorescence alterations associated with atezolizumab administration. ATP exhibited a more pronounced protective effect than taxifolin under the conditions of this experimental model. Nevertheless, further experimental studies are required to elucidate the mechanisms underlying these effects.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026The role of adenosine triphosphate in the treatment of linezolid-induced ovarian damage and reproductive dysfunction in rats: An investigation into the pathogenesis
Delibasi, Ilhan Bahri; Yavuzer, Bulent; Suleyman, Bahadir; Gumusburun, Neset; Coban, Taha Abdulkadir; Mendil, Ali Sefa; Uyar, Elif Esra; Yucel, Nurinisa; Suleyman, Halis
Linezolid is an oxazolidinone-derived antibacterial agent that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This study investigated whether exogenously administered adenosine triphosphate (ATP) mitigates ovarian damage and reproductive dysfunction induced by linezolid in rats. Forty-eight female albino Wistar rats were randomly assigned to four groups (n = 12 each): healthy control (HG), ATP-only (ATPG), linezolid-only (LZDG), and ATP plus linezolid (ATLDG). ATPG and ATLDG received intraperitoneal ATP (4 mg/kg), whereas HG and LZDG received saline (0.9 % NaCl). One hour later, linezolid (125 mg/kg) was administered orally to LZDG and ATLDG, and the regimen was repeated twice daily for 28 consecutive days. At study end, six rats per group were euthanized for ovarian biochemical, histopathological, and immunohistochemical evaluations; prior to euthanasia (i.p. thiopental sodium, 50 mg/kg), blood was collected for serum prolactin and anti-Müllerian hormone (AMH) analysis. For fertility assessment, the remaining six females per group were co-housed with two proven fertile males for seven days and then monitored for pregnancy for one month. Linezolid exposure increased oxidative stress, caused ovarian tissue injury, decreased AMH, elevated prolactin, and resulted in a 66.7 % infertility rate. ATP co-treatment attenuated these alterations and reduced infertility to 33.3 %. These findings suggest that ATP may provide a protective therapeutic approach against linezolid-induced ovarian toxicity and reproductive dysfunction.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026A Comparative Evaluation of the Therapeutic Effects of Adenosine Triphosphate, Coenzyme Q10, Pyridoxine, and Thiamine Pyrophosphate in a Linezolid-Induced Peripheral Neuropathic Pain Model in Rats
Ozgodek, Habip Burak; Ince, Ramazan; Kahramanlar, Agah Abdullah; Yavuzer, Bulent; Sezgin, Esra Tuba; Mammadov, Renad; Bakan, Nuri; Suleyman, Halis
Background/Objectives: Linezolid is an oxazolidinone antibiotic whose prolonged use is associated with peripheral neuropathy, hyperlactatemia, and metabolic acidosis. These adverse effects are primarily linked to the inhibition of mitochondrial protein synthesis, respiratory chain dysfunction, and oxidative stress. Given the central role of impaired energy metabolism and redox imbalance in drug-induced peripheral neuropathy, therapeutic strategies targeting mitochondrial function are of particular interest. Accordingly, this study aimed to comparatively evaluate the effects of adenosine triphosphate (ATP), coenzyme Q10 (CoQ10), pyridoxine, and thiamine pyrophosphate (TPP) on linezolid-induced peripheral neuropathic pain in rats. Methods: Sixty male albino Wistar rats were assigned to ten groups: healthy (HG); ATP-only (ATPG, 5 mg/kg, intraperitoneally); CoQ10-only (CQ10G, 10 mg/kg, orally); pyridoxine-only (PDXG, 50 mg/kg, orally); TPP-only (TPPG, 20 mg/kg, intraperitoneally); linezolid-only (LZDG, 125 mg/kg, orally); linezolid+ATP (ATLG); linezolid+CoQ10 (CQLG); linezolid+pyridoxine (PXLG); and linezolid+TPP (TPLG). Treatments were administered once daily for ATP, CoQ10, and TPP, and twice daily for linezolid and pyridoxine for 14 days. Oxidative stress indices (MDA, tGSH, SOD, CAT) were quantified in the sciatic nerve using ELISA. Serum lactate dehydrogenase (LDH) activity and blood lactate levels were determined to evaluate metabolic disturbances. Mechanical paw withdrawal thresholds were measured using the Randall–Selitto test both before and after treatment. Results: Linezolid significantly reduced paw withdrawal thresholds and induced oxidative stress, antioxidant depletion, increased LDH activity, and hyperlactatemia. Co-treatment with ATP and CoQ10 attenuated oxidative stress but did not significantly improve linezolid-induced reductions in nociceptive thresholds. In contrast, pyridoxine partially alleviated linezolid-induced neuropathic pain and improved biochemical parameters. Notably, TPP exerted the most robust protective effect, preserving nociceptive thresholds and effectively normalizing oxidative stress and metabolic indices. Conclusions: These findings identify TPP as a promising therapeutic strategy for mitigating linezolid-induced peripheral neuropathic pain by targeting mitochondrial energy metabolism and pyruvate–lactate homeostasis.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Pilot Study on the Effects of First-Line Antituberculosis Drugs and Their Combinations on Selected Reproductive Endpoints in Female Rats
Uyar, Elif Esra; Yavuzer, Bulent; Babayeva, Mansura; Yucel, Nurinisa; Gunay, Murat; Suleyman, Halis
Background: The reproductive toxicity of first-line antituberculosis drugs remains poorly understood, particularly when used in combination. Rifampicin, isoniazid, pyrazinamide, and ethambutol are essential in tuberculosis therapy, but their potential influence on female fertility is uncertain. This pilot study evaluated their effects, given alone or in dual, triple, and quadruple combinations, on oxidative stress, endocrine markers, and reproductive outcomes in healthy female rats. Materials and Methods: Ninety-six albino Wistar-type female rats were divided into sixteen groups of six animals each and treated with single, dual, triple, or quadruple regimens of first-line antituberculosis drugs for 28 days. After treatment, two sexually mature males were introduced per group, and therapy continued for seven additional days. Serum malondialdehyde (MDA), total glutathione (tGSH), prolactin, and anti-Mullerian hormone (AMH) levels were measured, and fertility outcomes were evaluated. Results: In single-drug groups, MDA increased and tGSH decreased, but detectable infertility was not recorded. Prolactin remained stable except in the pyrazinamide group, where it declined. Dual-drug regimens increased oxidative imbalance; fertility failure occurred only in pyrazinamide-lacking groups and was accompanied by higher prolactin and lower AMH. Triple and quadruple combinations produced prominent oxidative imbalance. In triple-drug regimens, infertility was lower in pyrazinamide-containing groups than in the pyrazinamide-free group, but this pattern was not maintained in the quadruple regimen. Fertility impairment was not consistently aligned with the degree of oxidative stress and may involve prolactin and AMH alterations. Conclusions: These findings suggest that reproductive impairment under these experimental conditions may involve endocrine alterations and cannot be explained solely by serum oxidative imbalance. Pyrazinamide-associated fertility preservation appeared context-dependent and requires further confirmation in larger mechanistic studies with broader reproductive and endocrine assessment.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Comparative Study on the Protective Effect of Thiamine and Thiamine Pyrophosphate Against Hydroxychloroquine-Induced Cardiomyopathy in Rats
Emir, Izzet; Yavuzer, Bulent; Suleyman, Bahadir; Sarigul, Cengiz; Mendil, Ali Sefa; Sezgin, Esra Tuba; Altuner, Durdu; Gursul, Cebrail; Suleyman, Halis
Background: Hydroxychloroquine (HCQ), widely used in autoimmune and inflammatory diseases, has been associated with cardiotoxicity driven by oxidative, mitochondrial, and metabolic disturbances. However, no comparative evidence exists regarding whether thiamine, thiamine pyrophosphate (TPP), or their combination (TTPC) can mitigate HCQ-induced myocardial injury. Objective: This study examined the biochemical and histopathological effects of thiamine, TPP, and their combination in a rat model of HCQ-induced cardiomyopathy. Methods: Thirty male Wistar rats were assigned to five groups: healthy control, HCQ, thiamine + HCQ, TPP + HCQ, and TTPC + HCQ. Thiamine (20 mg/kg, intraperitoneal), TPP (20 mg/kg, intraperitoneal), or TTPC (20 mg/kg each, intraperitoneal) was administered once daily, followed by HCQ (120 mg/kg, oral, twice daily). After seven days, cardiac tissue was analyzed for MDA, tGSH, SOD, and CAT, while serum TnI, lactate, and LDH were measured from tail-vein blood samples. Cardiac samples underwent histopathological examination. Results: HCQ exposure markedly increased MDA, TnI, LDH, and lactate levels while reducing tGSH, SOD, and CAT, indicating severe oxidative and metabolic insult. Thiamine co-treatment failed to ameliorate these disturbances. Conversely, TPP restored redox balance, attenuated biomarker elevations, and improved cardiac biochemical profiles. TTPC produced comparable improvements but did not exceed those of TPP alone. Histopathologically, HCQ caused pronounced myocyte degeneration and mononuclear infiltration, whereas TPP and TTPC groups showed only mild inflammatory changes with preserved myocardial architecture. Conclusions: HCQ induces a marked redox imbalance accompanied by well-defined histopathological myocardial degeneration. TPP afforded robust cardio-protection, whereas thiamine offered no meaningful benefit. Collectively, these findings position TPP as a biologically plausible, clinically relevant candidate for mitigating HCQ-induced cardiomyopathy.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Protective Effects of Ranolazine in a Rat Model of Ovarian Ischemia/Reperfusion Injury
Admis, Mesut; Sezgin, Esra Tuba; Suleyman, Zeynep; Admis, Ozlem; Ozkaraca, Mustafa; Gungor, Ali; Aliyev, Aydin; Suleyman, Halis
Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Comparative Protective Effects of Anakinra and Tocilizumab in Experimental Ocular Ischemic Syndrome
Karimov, Shavkatbek; Sezgin, Esra Tuba; Mammadov, Renad; Suleyman, Bahadir; Yaqudov, Kamandar; Yazici, Gulce Naz; Coban, Taha Abdulkadir; Suleyman, Halis; Bayrakceken, Kemal
Ocular ischemic syndrome (OIS) is a vision-threatening disorder characterized by retinal ischemia, oxidative stress, and inflammation. In this study, the protective effects of anakinra, an interleukin-1 receptor antagonist, were investigated and compared with those of tocilizumab, an interleukin-6 receptor antagonist. Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): sham-operated (SG), carotid artery clamping/unclamping (CUG), anakinra-treated carotid artery clamping/unclamping (ACUG), and tocilizumab-treated carotid artery clamping/unclamping (TCUG). An experimental ocular ischemic injury model induced by transient bilateral common carotid artery occlusion was established by transient bilateral common carotid artery clamping followed by reperfusion. Retinal tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels, and histopathological examinations were performed. OIS markedly increased MDA, TNF-α, IL-1β, and IL-6 levels while significantly decreasing tGSH, SOD, and CAT activities. Both anakinra and tocilizumab attenuated oxidative stress and inflammatory responses; however, anakinra produced notably greater improvements in MDA, tGSH, SOD, and CAT levels. Histopathological evaluation demonstrated that both treatments reduced retinal injury, edema, vascular congestion, and inflammatory cell infiltration. Although retinal architecture appeared slightly better preserved in the anakinra-treated group, histopathological scores were comparable between the treatment groups. These findings suggest that anakinra may attenuate oxidative and inflammatory retinal damage in this experimental ocular ischemic injury model and may provide greater biochemical protection than tocilizumab, whereas histopathological protection was comparable between treatments. Nevertheless, further experimental and clinical studies are required to confirm these findings.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Syringic acid pretreatment potentiates antioxidant mechanism and downregulates inflammatory signaling towards doxorubicin-related oxidoinflammatory hepatorenal damage in rats
Karadogan, Muhammed Talha; Yeni, Yesim; Yeter, Bahtinur; Gungor, Ali; Altuner, Durdu; Azade, Faraz; Gursul, Cebrail; Suleyman, Halis
Although doxorubicin (DOX) is a first-line antineoplastic drug, its clinical use is limited due to its widespread side effects. Hepatic and renal metabolic clearance causes DOX accumulation in these organ systems, ultimately leading to oxidative-inflammatory damage. This study investigated the potential impact of syringic acid (SA), a natural antioxidant phenolic compound, against in vivo DOX-evoked hepatorenal damage. SA was orally administered to rats at 100 mg/kg body weight for 10 consecutive days. On the 8th day of the study, DOX was administered at 20 mg/kg by single-dose intraperitoneal injection to prompt hepatorenal toxicity. Hepatorenal toxicity was assessed by measuring serum alanine transferase (ALT), aspartate transferase (AST), blood urea nitrogen (BUN), and creatinine (Cre). Histopathological evaluation of kidney and liver tissues was also performed to observe DOX-related damage. The concentrations of malondialdehyde (MDA) and glutathione (GSH), along with the activities of catalase (CAT) and superoxide dismutase (SOD), were measured in the hepatorenal tissues, in addition to the concentration of 8-OHdG in serum, to determine the protective effect of SA against oxidative stress. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were investigated with molecular and immunohistochemical analysis in hepatorenal tissues, evaluating the inflammation. SA treatment prevented DOX-aberrant elevation of hepatorenal biomarkers in serum, besides histopathological alterations in rats’ liver and kidney. Additionally, SA markedly counteracted DOX-provoked oxidative damage as evidenced by outstanding reduction in lipid peroxidation and 8-OHdG, conjointly promoted GSH contents, and amelioration of activities of SOD and CAT. Similarly, SA-treated rats exhibited attenuation of hepatorenal inflammation via diminished TNF-α and IL-6 levels. SA exerted a hepatorenal protective effect in rats by exhibiting antioxidant and anti-inflammatory activities.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Modulatory role of endogenous adrenaline in propofol-related nociceptive responses in rats
Gozen, Fusun; Sezgin, Esra Tuba; Yavuzer, Bulent; Sarigul, Cengiz; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Suleyman, Halis
Introduction – Propofol is a short-acting intravenous hypnotic anesthetic widely used for sedation and the induction and maintenance of general anesthesia. Although it reliably produces unconsciousness, its intrinsic analgesic efficacy remains a subject of debate. Accumulating evidence indicates that propofol suppresses catecholaminergic activity, and inhibition of endogenous adrenaline may therefore limit its ability to modulate nociceptive processing. Accordingly, this study aimed to investigate the nociceptive suppressions of subhypnotic and anesthetic doses of propofol in rats and their relationship with endogenous adrenaline levels. Methods – Thirty-six male Wistar rats were randomly allocated into six experimental groups: healthy healthy control, subhypnotic-dose propofol (25 mg/kg; PRO-25, intraperitoneally), anesthetic-dose propofol (50 mg/kg; PRO-50, intraperitoneally), adrenaline-alone (0.3 mg/kg; ADRG, intraperitoneally), and adrenaline combined with subhypnotic or anesthetic-dose propofol (PRAD-25 and PRAD-50). Mechanical paw withdrawal thresholds, anesthetic duration, behavioral responses to standardized scalpel incision, and plasma adrenaline levels were evaluated using statistical analyses. Results – Propofol administered alone failed to produce significant nociceptive suppressionat either dose and induced dose-dependent suppression of circulating adrenaline, whereas adrenaline alone exerted no significant effect on nociceptive thresholds. In contrast, combined administration significantly increased pain thresholds at subhypnotic doses and abolished responses to surgical incision at anesthetic doses despite comparable anesthetic duration. Notably, co-administration restored serum adrenaline levels toward physiological values at lower, but not higher, propofol doses. Conclusion – These findings provide experimental results suggesting that nociceptive responses observed during propofol exposure may be modulated by endogenous adrenergic activity. This interaction may contribute to explaining the dissociation between anesthetic depth and nociceptive suppression and points to a catecholaminergic influence on anesthetic–nociceptive dynamics that has not been sufficiently investigated previously.
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