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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 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 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 - 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 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 Erişim2026The effect of Hippophae rhamnoides on Hydroxychloroquine-Induced stomatitis in rats
Dilber, Muhammet; Suleyman, Zeynep; Yucel, Nurinisa; Yazici, Gulce Naz; Mammadov, Renad; Cakir, Osman Kagan; Celik, Fatih; Coban, Taha Abdulkadir; Salcan, Ismail; Baykal, Huseyin
Background: Stomatitis is the most common mucosal side effect associated with Hydroxychloroquine (HCQ). Hippophae Rhamnoides (HR) is known to contain several phytonutrients, including anti-inflammatory, and antioxidant properties. This study aimed whether HR can mitigate HCQ-induced oxidative stress and inflammation in rat cheek tissue and to corroborate biochemical findings with macroscopic and histopathological evaluations. Methods: Twenty four rats were used and split into four groups: healthy control group (HG), receiving HR alone, receiving HCQ alone, and receiving both HR and HCQ (HRHQ). The drugs were administered for 10 days, and at the end of the 10th day, the rats were euthanized with high dose of thiopental sodium anesthesia and the inner cheek tissues removed. Results: HR decreased malondialdehyde, and pro-inflammatory cytokine levels, which increased by HCQ, while it increased anti-oxidant levels, which decreased by HCQ. The inner cheek tissue was examined macroscopically for edema, hemorrhagic cracks, hyperemia and gray appearance that developed due to HCQ use, which were alleviated with HR. Histopathologically, epithelial necrosis, muscle degeneration, scar tissue, polymorphonuclear cell (PMNL) infiltration, haemorrhage and edema were observed in the HCQ group. In contrast, in the HRHQ group, epithelial necrosis, and muscle degeneration were normal, haemorrhage was absent, PMNL infiltration persisted in some-areas, and moderate capillary congestion and dilatation were observed. detected. Conclusion: The results indicate that HR may be a potential candidate for preventing and treating stomatitis associated with HCQ use. Translating these findings into clinical practice could support the safe and effective use of HR as a therapeutic agent.
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 künye2025Effect of elamipretide and methylprednisolone treatment on optic nerve, retina and brain damage in a methanol poisoning model: biochemical and histopathological evaluation
Bulbul, Ozlem; Mammadov, Renad; Suleyman, Bahadır; Kulaber, Ali; Karaca, Yunus; Yaman, Huseyin; Yenilmez, Engin; Sahin, Aynur; Ozer, Vildan
Purpose: This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity. Method: In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration. Results: In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009). Conclusion: Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025The effect of methylphenidate on the reproductive function of female rats
Cim, Numan; Cim, Bunyamin; Akyuz Cim, Emine Fusun; Bulut, Seval; Mammadov, Renad; Suleyman, Bahadır; Yucel, Nurinisa; Mendil, Ali Sefa; Coban, Taha Abdulkadir; Suleyman, Halis
Aim: Research on the effects of methylphenidate on female fertility is limited. This study evaluated the effects of methylphenidate on reproductive function, oxidants, antioxidants, proinflammatory cytokines, prolactin, and cortisol in female rats. Methods: Forty-eight albino Wistar female rats were divided into four groups consisting of 12 rats, which were given pure water orally once daily for 7 days (HG-1), 10 mg/kg methylphenidate orally once daily for 7 days (MP-1), pure water orally once daily for 30 days (HG-2), and 10 mg/kg methylphenidate orally once daily for 30 days (MP-2). At the end of the treatment periods, tail vein blood was collected from six rats per group for prolactin and cortisol determination. Subsequently, euthanasia was performed and the ovaries were removed. Ovaries were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), and immunohistochemically. For breeding, the remaining six rats were mated with male rats for 1 month. Rats that failed to give birth were classed as infertile. Results: A comparison of MP-1 and MP-2 groups to healthy controls revealed an elevation in MDA and corticosterone levels, and a decline in tGSH, SOD, and CAT levels (p < 0.001). Methylphenidate did not affect prolactin, IL-1β, and TNF-α levels (p > 0.05). MP-1 and MP-2 exhibited immunopositivity for 8-hydroxy-2'-deoxyguanosine (8-OHDG). MP-2 rats developed 66.7% infertility while MP-1, HG-1, and HG-2 rats did not. Conclusion: In ovaries, methylphenidate caused oxidative stress, but did not induce inflammation. Long-term use of methylphenidate caused increased cortisol levels and infertility.
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 - ArticleAçık Erişim2025The role of antioxidant and anti-inflammatory mechanisms in the protective effects of vigabatrin against ovarian ischemia-reperfusion injury in a rat model
Hizal, Elif; Uyar, Esra; Bingul, Eda; Cicek, Betul; Demir, Özlem; Mammadov, Renad; Sarigul, Cengiz; Gursul, Cebrail; Suleyman, Halis
Background: Exposure of ovarian tissue to ischaemia and subsequent reperfusion can result in oxidative and inflammatory damage. A decline in adenosine triphosphate (ATP) levels has the potential to initiate pathological processes and compromise antioxidant defence mechanisms. Vigabatrin, an antiepileptic agent, has been shown to increase levels of gamma-aminobutyric acid (GABA). GABA has the potential to increase ATP levels. The present study was conducted to evaluate the preventive effects of vigabatrin concerning ovarian ischaemia-reperfusion (I/R) injury. Methods: The experiment comprised the allocation of thirty female Wistar albino rats into five groups: a sham operation group (SOG), a vigabatrin group (VIG), an ovarian I/R group (OIR), a vigabatrin + sham operation group (VISO), and a vigabatrin + ovarian I/R group (VOIR). Surgical procedures were performed under anesthesia. The VIG and VOIR were given vigabatrin (50 mg/kg, orally). Following a period of anticipation spanning an hour, the ovaries of the SOG, OIR, and VOIR rats were accessed via an abdominal incision. The incision site was sutured without the performance of an I/R procedure on the SOG ovaries. In the OIR and VOIR, the right ovaries were subjected to three hours of ischemia, followed by six days of reperfusion. Drug treatment was administered once a day using the same method for six days. Then, the rats were euthanised with 120 mg/kg ketamine (intraperitoneally). The ovarian tissues were removed. These samples were examined for oxidants, antioxidants, and proinflammatory cytokines. Results: The I/R procedure caused an increase in malondialdehyde, tumour necrosis factor alpha, interleukin 1β, and interleukin 6 levels, as well as a diminish in total glutathione, superoxide dismutase, and catalase in the ovaries, compared to the SOG (p < 0.001). Moreover, in the present study, I/R was found to result in changes in follicle numbers, as well as congestion, dilatation of the vessels, edema, and an increase in inflammatory cells (p < 0.05). In comparison with OIR, VOIR demonstrated a decline in oxidants and proinflammatory cytokines, an augmentation in antioxidants, and a reduction in histopathological damage(p < 0.05). Conclusion: It is proposed that vigabatrin may represent a novel strategy for the prevention of ovarian injury associated with I/R. Clinical trial number: Not applicable.
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 Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
Bedir, Fevzi; Kocatürk, Hüseyin; Altay, Mehmet Sefa; Mammadov, Renad; Süleyman, Bahadır; Coban, Taha Abdulkadir; Yazici, Gülce Naz; Bulut, Seval; Süleyman, Halis
Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
Ates, Irem; Isik, Bahar; Gozen, Fusun; Yazici, Gulce Naz; Gulaboglu, Mine; Mammadov, Renad; Huseynova, Gulbeniz; Altuner, Durdu; Suleyman, Halis
Background: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against serotonin syndrome that may occur with serotoninergic drugs such as tramadol and citalopram. Methods: Rats were divided into eight groups (n = 6) that received tramadol (50 mg/kg), citalopram (10 mg/kg), or tianeptine (5 mg/kg) alone or a combination of tramadol + citalopram, tramadol + tianeptine, citalopram + tianeptine or tramadol + citalopram + tianeptine at the same doses administered to the stomach by oral gavage for 3 weeks. The healthy control group was given saline. Malondialdehyde, total glutathione, superoxide dismutase, and catalase levels were measured in removed brain tissues. The tissues were also examined histopathologically. Results: In the tramadol, tramadol + citalopram, and tramadol + citalopram + tianeptine groups, malondialdehyde levels were found to be higher compared to the control group, while glutathione, superoxide dismutase, and catalase levels were found to be lower. In other groups, values close to the control group were measured. Morphological degeneration was observed in neurons in the tramadol + citalopram group. The swelling of astrocytes and pericellular edema in oligodendrocytes were also observed. A significant population increase was noted in microglial cells. Blood vessels belonging to the tissue were observed to be severely dilated and congested. Histopathological damage was partially resolved in the group given tramadol + citalopram + tianeptine. Conclusions: The tramadol + citalopram combination caused severe oxidative stress in brain tissue. Tramadol alone caused mild damage in brain tissue, whereas tianeptine prevented the brain damage caused by tramadol.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Role of Oxidant and Proinflammatory Cytokines and the Effect of Leflunomide in the Pathogenesis of Ovarian IschemiaReperfusion Injury
Isaoglu, Unal; Uyar, Elif Esra; Sahin, Nurullah; Bulut, Seval; Mammadov, Renad; Yilmaz, Betul Kalkan; Gunay, Murat; Mendil, Ali Sefa; Suleyman, Halis
Background and Objective: Ischemia-reperfusion (IR) causes tissue damage by inducing oxidative stress and inflammation. In this study, the protective ability of leflunomide, which is reputed to have antioxidant and anti-inflammatory effects, against IR-induced ovarian damage in rats was researched. Materials and Methods: Twenty-four albino Wistar female rats were divided into 4 groups of six each: Healthy (HG), sham-operated (SOG),ovarian IR (OIR) and leflunomide+ovarian IR (LOIR).One hour beforethe IR procedure, the LOIRgroup received 10 mg/kg leflunomide orally. Ovaries of rats in OIR and LOIR groups were subjected to 3 hrs ischaemia and 6 hrs reperfusion. For six days, leflunomide were implemented once a day. On day seven, the animals were euthanized and their ovaries were collected. The tissues were examined biochemically and histopathologically. Results: Leflunomide treatment significantly suppressed IR-induced rise in malondialdehyde (MDA),Tumor Necrosis Factor-Alpha (TNF-) and Interleukin 6 (IL-6) and the decline in Total Glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) (p<0.001). Severe stromal hemorrhage, edema and follicular hemorrhage were noted in the ovaries of the IR group. Leflunomide treatment significantly prevented IR-induced ovarian tissue damage (p<0.05). Conclusion: Leflunomide could protect the ovaries with antioxidant and anti-inflammatory activity in ovarian IR injury.
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.
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