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- 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 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 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 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 - 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 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 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 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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Pretreatment of trans-ferulic acid improved neurotoxicity in a thioacetamide-induced hepatic encephalopathy rat model; participation of the MAPK/NF-κb signaling pathway
Kilic, Adil Furkan; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Mendil, Ali Sefa; Suleyman, Halis
Aim – Trans-ferulic acid (TFA), a naturally occurring phenolic compound, has attracted significant attention due to its strong hepatoprotective and neuroprotective properties. Despite extensive research on its overall biological activities, the specific mechanisms by which TFA influences hepatic encephalopathy (HE) remain unclear. This study aims to explore the therapeutic potential of TFA by examining its effects on inflammatory signaling, glial activation, and apoptotic pathways in a thioacetamide (TAA)-induced rat model of HE. Methods – Rats were separated into four groups: a normal control group, the TAA group (which received TAA at 300 mg/kg/day for 3 days), and groups pre-treated with TFA (at doses of 25/50 mg/kg, administered orally) for 10 days, with TAA administered from the eighth to the 10th day. Results – TFA pre-treatment effectively reduced TAA-induced biochemical disturbances, as shown by lower serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and ammonia. This biochemical improvement was complemented by a significant reduction in TAA-related hepatic histopathological damage. TFA also alleviated systemic inflammation by suppressing TAA-induced increases in pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), while also elevating the anti-inflammatory cytokine IL-10. Consistent with these results, TFA further suppressed the activation of MAPK/NF-κB inflammatory signaling pathways in both liver and brain tissues and decreased glial fibrillary acidic protein (GFAP) expression in the brains of TAA-treated rats, indicating reduced neuroinflammation and astrocyte activation. Additionally, immunochemical analysis showed that TFA pre-treatment effectively prevented the TAA-induced increase in pro-apoptotic markers Caspase-3 and Bax in both liver and brain tissues. This study underscores the strong protective effects of TFA against TAA-induced HE, mainly through inhibition of MAPK/NF-κB signaling, suppression of astrocyte activation, and reduction of apoptosis. Conclusion – These outcomes imply that TFA could be an effective treatment for HE.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026A Novel Protective Strategy Against Metformin-Induced Renal Injury Involving Adenosine Triphosphate and Thiamine Pyrophosphate
Kocaturk, Huseyin; Bedir, Fevzi; Yavuzer, Bulent; Sezgin, Esra Tuba; Mammadov, Renad; Suleyman, Bahadir; Sarigul, Cengiz; Cimen, Ferda Keskin; Altay, Mehmet Sefa; Suleyman, Halis
Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine pyrophosphate (TPP) remain poorly defined. This study aimed to evaluate whether ATP and TPP mitigate metformin-induced renal injury through biochemical and histopathological assessments. Wistar rats were randomly divided into six groups: control, ATP, TPP, metformin, ATP + metformin, and TPP + metformin. Metformin (50 mg/kg, oral), ATP (4 mg/kg, intraperitoneal), or TPP (20 mg/kg, intraperitoneal) was administered daily for 10 days. Oxidative stress markers, inflammatory cytokines, renal histopathology, and serum creatinine, BUN, lactate, and LDH levels were evaluated. Metformin induced significant oxidative stress, inflammation, metabolic disturbance, and renal injury. ATP provided partial protection, whereas TPP markedly restored redox balance, reduced inflammation, and preserved renal histology. TPP confers superior protection against metformin-induced renal injury compared with ATP by modulating oxidative, inflammatory, and metabolic pathways, highlighting its therapeutic potential in preventing metformin-related nephrotoxicity.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Potential effects of adenosine triphosphate and melatonin on oxidative and inflammatory optic nerve damage in rats caused by 5-fluorouracil
Somuncu, Ahmet Mehmet; Somuncu, Busra Parlak; Ozbay, Ahmet Duhan; Cicek, Ibrahim; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Suleyman, Halis
• AIM: To investigate the effects of adenosine triphosphate (ATP) and melatonin, which have antioxidant and anti-inflammatory activities, on potential 5-fluorouracil (5-FU)-induced optic nerve damage in rats. • METHODS: Twenty-four rats were categorized into four groups of six rats: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), and melatonin+5-FU (MFU). ATP (4 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally and orally, respectively. One hour after ATP and melatonin administration, rats in the AFU, MFU, and FUG were intraperitoneally injected with 5-FU (100 mg/kg). ATP and melatonin were administered once daily for 10d. 5-FU was administered at a single dose on days 1, 3, and 5 of the experiment. After 10d, the rats were euthanized and optic nerve tissues were extracted. Optic nerve tissues were biochemically and histopathologically examined. • RESULTS: ATP and melatonin treatments inhibited the increase in malondialdehyde (MDA) and interleukin-6 (IL-6) levels, which were elevated in the FUG. The treatments also prevented the decrease in total glutathione (tGSH) levels and the superoxide dismutase (SOD) and catalase (CAT) activities (P<0.001). This inhibition was higher in the ATP group than in the melatonin group (P<0.001). ATP prevented histopathological damage better than melatonin (P<0.05). • CONCLUSION: ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage. In addition, ATP treatment shows better protective effects than melatonin.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Hormonal mechanism and pathogenetic therapy of citalopram-induced infertility in female rats
Delibasi, Ilhan Bahri; Gumusburun, Neset; Bulut, Seval; Mammadov, Renad; Yilmaz, Betul Kalkan; Suleyman, Bahadir; Bakan, Nuri; Mendil, Ali Sefa; Suleyman, Halis; Altuner, Durdu
Citalopram is a selective serotonin reuptake inhibitor (SSRI) and has been associated with reproductive dysfunction in women. In this study, the effects of citalopram on reproductive health in female rats were investigated. Albino Wistar rats was divided into six groups (each group/n = 12): healthy (HG), citalopram (CTP), cabergoline (CBR), metyrapone (MTP), cabergoline+citalopram (CBR+CTP), and metyrapone+citalopram (MTP+CTP). Initially, cabergoline 0.1 mg/kg and metyrapone 50 mg/kg were administered orally. A dose of 10 mg/kg of citalopram was given orally one hour later. For 30 days, the treatment protocol was applied once a day. Then, blood samples were taken from the tail veins of six rats from each group for prolactin and corticosterone analyses and ovaries were removed after euthanasia. The ovaries were examined for oxidants and antioxidants and histopathologically. During two months, the remaining animals were kept with male rats. The rats that did not deliver during this period were considered infertile. In terms of oxidants and antioxidants, there was no significant difference between the groups (p > 0.05). In half of the female rats, citalopram caused infertility, increased levels of prolactin and corticosterone, and damaged the ovaries histopathologically (p < 0.05). Cabergoline suppressed the elevation of prolactin by citalopram (p < 0.001) but did not prevent infertility. In contrast, metyrapone significantly prevented the citalopram-induced increase in corticosterone, infertility, and tissue damage induced by citalopram (p < 0.05). According to the results of our study, the preventive effect of drugs that suppress excessive corticosterone on citalopram-induced infertility in rats may be encouraging for further clinical studies.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats
Ekici, Ozgur; Gul, Abdullah; Keskin, Ercument; Bulut, Seval; Suleyman, Bahadir; Mammadov, Renad; Cicek, Betul; Demir, Ozlem; Gunay, Murat; Suleyman, Halis
Background: An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Methods: Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10 mg/kg) and CE (100 mg/kg) were orally given. After 1 h, 50 mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10 days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Results: Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Conclusion: Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025The Protective Effect of Thiamine and Thiamine Pyrophosphate Against Linezolid-Induced Oxidative Liver Damage and Lactic Acidosis in Rats
Isik, Bahar; Ates, Irem; Yucel, Nurinisa; Suleyman, Bahadir; Mendil, Ali Sefa; Sezgin, Esra Tuba; Suleyman, Halis
Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. Therefore, this study aimed to evaluate the protective effect of TPP against possible linezolid-induced liver damage and lactic acidosis in rats. Twenty-four male Wistar albino rats were randomly assigned to four groups (n = 6): healthy control (HG), linezolid (LZD), thiamine plus linezolid (TLZD), and TPP plus linezolid (TPLZD). Thiamine and TPP (20 mg/kg, intraperitoneal (i.p.)) were administered once daily, while linezolid (125 mg/kg, per os (p.o.)) was given twice daily (250 mg/kg/day) for 28 days. Animals were euthanized under high-dose anesthesia (with 50 mg/kg, i.p. thiopental sodium). Liver tissues were analyzed for MDA, tGSH, SOD, and CAT, and examined histopathologically. Blood samples were collected prior to euthanasia to assess lactate, LDH, ALT, AST, and TPP levels. In the LZD group, MDA, lactate, ALT, AST, and LDH levels significantly increased, while tGSH, SOD, CAT, and TPP decreased (p < 0.001). Histopathology showed hydropic degeneration, necrosis, and mononuclear cell infiltration (p < 0.05). Thiamine did not prevent these alterations (p > 0.05), whereas TPP significantly prevented both biochemical and histopathological changes (p < 0.05), indicating its protective efficacy. TPP may offer significant protection against linezolid-induced hepatotoxicity and lactic acidosis.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Revealing the protective potential of D-(-)-Quinic acid against thioacetamide-induced hepatic encephalopathy in rats
Ciftel, Sedat; Cicek, Betul; Bolat, Ismail; Bulut, Seval; Yildirim, Serkan; Suleyman, Bahadir; Qaniyev, Musa; Süleyman, Halis
The objective of this study was to elucidate the impact of D-(-)-Quinic acid (D-(-)-QA), a natural phenolic acid, on the molecular mechanisms of inflammation and oxidative stress in brain and liver damage in thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats. To establish an experimental HE model, rats were injected with three doses (200 mg/kg, intraperitoneally) of TAA every other day, followed by the administration of D-(-)- QA (200 or 400 mg/kg, orally) for fourteen days. Serum ammonia, alanine transaminase (ALT), and aspartate transaminase (AST) levels were detected. Tumor necrosis factor (TNF-α), interleukin-1beta IL-1β, and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were analyzed to assess inflammation and oxidative damage in brain and liver tissues. Histopathological examinations, immunofluorescence (PI3K and AKT expressions), and immunohistochemical (HSP70 expression) examinations were also performed. TAA administration causedhyperammonemia and increased ALT and AST levels, along with histopathological changes indicating damage to hepatocytes and neurons. Additionally, it disrupted the inflammatory response and promoted oxidative damage by activating the PI3K/AKT-related HSP70 response in the brain and liver. Treatment with D-(-)-QA significantly prevented the increase in ammonia levels and improved the liver function. In addition, the increase in TNF-α, and IL-1β, proinflammatory cytokines in liver and brain tissues as well as the increase in MDA and decrease in SOD and GSH were significantly suppressed by D-(-)-QA. By suppressing HSP70 and PI3K/AKT signaling in brain and liver tissues, D-(-)-QA administration attenuated inflammation and oxidative damage. D-(-)-QA may be an alternative to current clinical interventions by inhibiting inflammation and oxidative damage signaling toward the pathogenesis of HE.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Effect of Sugammadex on Ischemia-Reperfusion-Induced Oxidative and Inflammatory Ovarian Damage in Rats: Biochemical and Histopathological Evaluation
Kadioglu, Berrin Goktug; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Altuner, Durdu; Yazici, Gulce Naz; Gulaboglu, Mine; Suleyman, Halis
Background and Objective: Polymorphonuclear leukocytes (PMNLs) play an important role in the pathogenesis of oxidative ischemia-reperfusion (I/R) damage. There is information that sugammadex inhibits PMNL infiltration into organs and tissues undergoing I/R. Present study aimed to investigate the potential protective effect of sugammadex against I/R-induced ovarian damage in rats and to elucidate its mechanism of action. Materials and Methods: The 24 female albino Wistar-type rats were divided into four groups as follows: Sham operation (SG), ovarian I/R (IRG), sugammadex (4 mg/kg) +ovarian I/R (SIR-4) and sugammadex (8 mg/kg) +ovarian I/R (SIR-8). Sugammadex was administered intraperitoneally. The animals were subjected to 2 hrs of ischemia followed by 2 hrs of reperfusion. Results: Sugammadex significantly inhibited the increase in I/R-induced malondialdehyde and the decrease in total glutathione, superoxide dismutase and catalase levels in ovarian tissue at a dose of 8 mg/kg compared with the dose of 4 mg/kg. Moderate follicular degeneration, vascular congestion, necrosis, oedema and hemorrhage were observed in the sugammadex (4 mg/kg) group, which significantly reduced the increase in I/R-related PMNL infiltration in ovarian tissue. Only mild vascular congestion was observed in the ovarian tissue of the 8 mg/kg sugammadex group, which did not show PMNL infiltration. Conclusion: Histopathological findings show that sugammadex protects ovarian tissue from oxidative and inflammatory injury of the I/R by inhibiting PMNL infiltration. Results also suggest that an 8 mg/kg dose of sugammadex, which completely inhibits PMNL infiltration into ovarian tissue, may be more beneficial than the 4 mg/kg dose in the treatment of I/R-induced ovarian damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Comparative Investigation of the Effects of Adenosine Triphosphate and Agomelatine Against Acrolein-Induced Oxidative and Inflammatory Lung Injury in Rats
Unver, Edhem; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Background and Objective: Acrolein-induced tissue damage has been attributed to oxidative stress and inflammation.This study aimed to determine the effects of adenosine triphosphate (ATP) and agomelatine, two substances known to have antioxidant and antiinflammatory effects, separately and in combination, on possible acrolein-induced lung damage in rats. Materials and Methods: There were 30 albino Wistar rats divided into five groups of six: Healthy (HG), acrolein (AC), ATP+acrolein (ATAC), agomelatine+acrolein (AGAC) and ATP+agomelatine+acrolein (AAAC). The dose of ATP administered intraperitoneally was 4 mg/kg and the dose of agomelatine administered orally was 25 mg/kg. An oral dose of acrolein 3 mg/kg was given 1 hr following the administration of ATP and agomelatine. For 30 days, the treatment protocol was followed once a day. Afterwards, the rats were euthanized and their lungs were removed. Oxidants, antioxidants and pro-inflammatory cytokines were measured in lung tissues. Results: In lung tissues, acrolein increased malondialdehyde, nuclear factor kappa, tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). The ATP+agomelatine, ATP and agomelatine treatments were the most effective at preventing these biochemical changes, respectively (p<0.001). As a result, the biochemical data of the HG and AAAC groups were similar (p>0.05). Conclusion: It could be suggested that both ATP and agomelatine might be effective against the pneumotoxic effects of acrolein, though a combination therapy would be more effective.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats
Isik, Bahar; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Yavuzer, Bulent; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Background: The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. Aims: In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Methods: Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100 mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150 mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7 days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. Results: CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusion: Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation; [Toxicidad pulmonar asociada a altas dosis de favipiravir y opciones de tratamiento: Evaluación bioquímica e histopatológica]
Elma, Bekir; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Unver, Edhem; Altuner, Durdu; Coban, Taha A.; Mokhtare, Behzad; Suleyman, Halis
Favipiravir is a broad-spectrum antiviral drug that is a viral RNA-dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidipine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Laci-dipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathi-one), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopatho-logically examined. The systemic administration of high doses of favipiravir in-creased oxidant levels and decreased antioxidant levels in the lung tissue of rats. In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mit-igating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine administration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against favipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.
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