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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 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 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 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 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 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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Experimental Investigation of Fentanyl Analgesic Potency and Its Relationship with Endogenous Adrenaline Levels in Rats
Ates, Irem; Isik, Bahar; Sezgin, Esra Tuba; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Purpose: Fentanyl is a synthetic opioid analgesic widely used in perioperative medicine due to its high analgesic potency and short duration of action. Previous studies suggest that the analgesic and anesthetic effects of fentanyl may be associated with endogenous catecholamine levels. This study aimed to evaluate the relationship between fentanyl’s analgesic potency and anesthesia duration and endogenous levels of adrenaline (ADR) and noradrenaline (NDR) in rats, as well as changes in oxidative stress and inflammation markers including malondialdehyde (MDA), total glutathione (tGSH), and interleukin-6 (IL-6). Patients and Methods: Three groups of six rats each were formed: an intact group receiving fentanyl, an intact group treated with metyrosine, and an adrenalectomized group receiving fentanyl. Fentanyl was administered at doses of 2, 15, 30, and 75 µg/kg, and anesthesia duration was recorded following intraperitoneal injection. Analgesic activity was assessed by measuring pain threshold using the paw pressure method, and immobility in the supine position was evaluated as an observational parameter. ADR, NDR, MDA, tGSH, and IL-6 levels were biochemically measured in blood and tissue samples. Results: Fentanyl produced analgesic effects in all experimental groups. However, no distinct anesthetic effect sufficient for surgical procedures was observed. Although the durations of immobility in the supine position were recorded, these observations were not evaluated as a direct measure of anesthetic duration. Different doses of fentanyl did not lead to significant alterations in oxidative stress parameters, antioxidant capacity, or anti-inflammatory cytokine levels across the groups. Conclusion: In conclusion, although the analgesic effect of fentanyl increased in a dose-dependent manner, it was found to be independent of serum ADR and NDR levels. High-dose fentanyl (75 µg/kg) did not induce anesthesia and did not significantly affect oxidative stress markers (MDA, tGSH) or IL-6 levels. The increase in MDA and the decrease in tGSH observed in the absence of adrenal hormones support their indirect antioxidant role. Overall, the findings indicate that fentanyl modulates catecholamine responses depending on dose and hormonal status, while its analgesic effect appears to be primarily mediated through µ-opioid receptor activation.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Effect of Hippophae Rhamnoides Fruit Extract on Doxorubicin-Induced Oxidative Brain Damage and Behavioral Impairment in Rats
Borekci, Taha Berkay; Altuner, Durdu; Cicek, Betul; Bulut, Seval; Coban, Abdulkadir Taha; Suleyman, Halis
Background and Objective: Doxorubicin (DOX) use can promote neurobehavioral changes and neurodegeneration, which have been attributed to oxidative stress. Thus, this study aimed to examine the effect of Hippophae rhamnoides L., fruit extract (HRe), against possible oxidative brain damage and behavioral disorders in rats caused by DOX.Materials and Methods: A total of 24 male Sprague-Dawley rats were utilized in this study and were divided randomly into four groups (n = 6 in each groups): CG, healthy control; HRe, 50 mg/kg HRe; DOX, 5 mg/kg i.p., in a single intraperitoneal dose of DOX; Hre + DOX, 50 mg/kg HRe + 5 mg/kg DOX. HRe was administered orally once a day for two weeks, while DOX was administered intraperitoneally twice a week for two weeks. Subsequently, behavioral tests were performed-the sucrose preference test (SPT) and pole test-to assess depression-like behaviors and motor function, respectively. Then, the level of oxidative stress was biochemically evaluated in the brain tissues of the rats. One-way analysis of variance (ANOVA) was conducted, followed by a post hoc Tukey's test for the statistical analysis. A p-value < 0.05 was considered statistically significant.Results: The HRe treatment markedly reduced DOX-induced depression-like behaviors and improved motor dysfunction. The HRe treatment also restored the impaired antioxidant response by inhibiting the DOX-related malondialdehyde increase and reducing the decrease in total glutathione levels, as well as superoxide dismutase and catalase activities.Conclusion: The present study indicates that HRe treatment has beneficial effects on motor dysfunction as well as depression-like behavior associated with neurodegeneration following DOX-induced brain damage. Possible mechanisms underlying these beneficial effects include lipid peroxidation inhibition and restoration of antioxidant defense mechanisms by HRe.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Dose-Dependent Pulmonotoxic Effects of Favipiravir in Rats Biochemical and Histopathological Evaluation
Suleyman, Zeynep; Altuner, Durdu; Suleyman, Halis; Coban, Taha Abdulkadir; Ozkaraca, Mustafa
Background and Objective: Favipiravir is associated with more serious side effects at higher doses. This experimental study proposed to investigate the effect of favipiravir on dose-dependent lung toxicity in rats biochemically and histopathologically. Materials and Methods: The rats were divided into four groups as healthy (HG), 100 mg/kg favipiravir (FAV-100), 200 mg/kg favipiravir (FAV-200) and 400 mg/kg favipiravir (FAV-400). Favipiravir 100, 200 and 400 mg/kg doses were administered by oral gavage to the other groups except HG. To the HG group, only distilled water (0.5 mL) was applied in the same way. This procedure was repeated twice a day for a week. Then, the rats were euthanised with high-dose anaesthesia and lung tissues were removed. Oxidative stress parameters such as malondialdehyde (MDA), Total Glutathione (tGSH), superoxide dismutase (SOD), total oxidant status (TOS) and total antioxidant status (TAS) were examined. After the one-way ANOVA, the Tukey's post hoc test was performed. Results: Favipiravir dose-dependently increased MDA and TOS also decreased tGSH, SOD and TAS in rat lung tissue. As favipiravir was given in increasing doses, it was easier to observe the changes between the different groups. This was also supported by the histopathological data. Histopathologically, interstitial pneumonia and lymphoid hyperplasia were mild in the 100 mg/kg favipiravir group, severe at high doses. Conclusion: As the dose of favipiravir increased, oxidant levels increased and antioxidant levels decreased in the lung tissue. In line with these results, it was observed that favipiravir caused a dose-dependent pulmonotoxic effect in rats.
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 Erişim2025Effects of adenosine triphosphate, thiamine pyrophosphate, melatonin, and liv-52 on subacute pyrazinamide proliferation hepatotoxicity in rats
Ciftel, Sedat; Ciftel, Serpil; Altuner, Durdu; Huseynova, Gulbaniz; Yucel, Nurinisa; Mendil, Ali Sefa; Sarigul, Cengiz; Suleyman, Halis; Bulut, Seval
Background: Hepatotoxicity of pyrazinamide, an antituberculosis drug, limits its therapeutic use and oxidative stress has been implicated in this toxicity. This study investigated the protective effects of adenosine triphosphate (ATP), thiamine pyrophosphate (TPP), melatonin, and Liv-52, which have previously been shown antioxidant activities, on pyrazinamide-induced hepatotoxicity. Methods: 36 albino Wistar male rats were divided into randomized six groups; healthy (HG), pyrazinamide (PZG), ATP + pyrazinamide (APZG), TPP + pyrazinamide (TPZG), melatonin + pyrazinamide (MPZG) and Liv-52 + pyrazinamide (LPZG) groups. ATP 4 mg/kg and TPP 25 mg/kg were administered intraperitoneally (IP). Melatonin 10 mg/kg and Liv-52 20 mg/kg were given orally. One hour after administration of ATP, TPP, melatonin, and Liv-52, 250 mg/kg pyrazinamide was applied orally to all rats except HG group. The treatment was repeated (1 × 1) for 4 weeks. Then, blood samples were taken for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Immediately after, the rats were euthanized with thiopental sodium (50 mg/kg, IP), and the livers were removed. The tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) also hydropic degeneration, necrosis, and apoptosis (caspase 3) were examined.One-Way ANOVA was used in biochemical analyses and Tukey test was used as post-hoc. For histopathological and immunohistochemical analysis, the Kruskal-Wallis test was used and Dunn’s test as a post-hoc. Results: Pyrazinamide increased MDA land decreased tGSH, SOD, and CAT levels in liver tissues (p < 0.001). It also increased serum ALT and AST activities and caused severe hydropic degeneration and necrosis in liver tissue (p < 0.001). ATP, TPP, melatonin, and Liv-52 significantly prevented the biochemical and histopathological changes induced by pyrazinamide (p < 0.05). On the other hand, Liv-52 was more successful than other potential protectors in protecting liver tissue from pyrazinamide damage (p < 0.05). Conclusions: ATP, TPP, melatonin, and Liv-52 can be used to protect liver tissue from pyrazinamide-induced hepatotoxicity in rats.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Protective effect of adenosine triphosphate against hydroxychloroquine ototoxicity in rats
Erhan, Ertugrul; Suleyman, Zeynep; Altuner, Durdu; Demir, Ozlem; Gulaboglu, Mine; Suleyman, Halis
One of the side effects of hydroxychloroquine is ototoxicity. This study examined the effect of adenosine triphosphate (ATP) on ototoxicity in rats treated with hydroxychloroquine (HCQ). In this study, 24 rats (male, albino Wistar) were used. The animals were divided into four groups: healthy control group (HG), ATP alone group (ATPG), HCQ alone group (HCQG), and ATP + HCQ (AHQG) group. The ATPG and AHQG groups were injected with ATP intraperitoneally (IP) at a dose of 4 mg/kg/day. The HG and HCQG groups were treated with the same volume of saline as the solvent by IP route. The AHQG group was administered HCQ orally at a dose of 120 mg/kg/day 1 h after the ATP and saline administration. This procedure was repeated daily for 10 days. The rats were euthanized (50 mg/kg thiopental sodium, IP) and after, vestibulocochlear nerve tissues were removed and the tissue oxidant and antioxidant parameters were studied. The tissues were also subjected histopathological examination. ATP significantly (p < 0.001) suppressed the increase in malondialdehyde associated with HCQ in vestibulocochlear nerve tissues as well as the decrease in total glutathione, superoxide dismutase, and catalase levels. ATP also reduced the severity of oedema, vascular congestion, dilatation, and collagen deposition in degenerated myelinated nerve fibers associated with HCQ. ATP is effective against oxidative damage associated with HCQ in vestibulocochlear nerve tissue.
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 - 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 Erişim2024ROLE OF L-, N- AND T-TYPE CALCIUM CHANNELS IN ACHIEVING MAXIMUM ANALGESIC AND MINIMUM TOXIC EFFECT OF TRAMADOL
Yi̇Lmaz, Mehmet; Suleyman, Bahadi̇R; Mammadov, Renad; Altuner, Durdu; Coban, Taha Abdulkadi̇R; Bulut, Seval; Coskun, Resi̇T; Suleyman, Hali̇S
The aim of the study was to investigate the effects of lacidipine, amlodipine, and benidipine on the analgesic activity and toxicity of tramadol. Rats (n = 6/each group) were divided into five groups as control (CG), tramadol (TRD), lacidipine+tramadol (LTRD), amlodipine+tramadol (ATRD), and benidipine+tramadol (BTRD). Tramadol was administered once at a dose of 50 mg/kg and lacidipine, amlodipin, benidipin were administered at a dose of 4 mg/kg orally, once a day for 10 days. After the animals were sacrificed, malondialdehyde (MDA) and total glutathione (tGSH) levels were measured in brain, heart, liver, and kidney tissues. Troponin I (Tp I), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were determined in serum. Paw pain thresholds were measured one hour before and after drug administration. The analgesic effect of tramadol was increased the most by benidipine, while amlodipine and lacidipine increased it equally. Lacidipine failed to suppress MDA increase and tGSH decrease in brain tissue. Benidipine suppressed MDA increase and tGSH decrease in brain tissue better than amlodipine. All three drugs suppressed cardiac tissue oxidative stress and the release of TP I into the circulation. Lacidipine and amlodipine could not prevent tramadol-induced oxidative stress in liver and kidney tissues, whereas benidipine prevented excessive MDA increase and tGSH decrease. Benidipine significantly suppressed the increase of ALT, AST, BUN, and creatinine. Analgesic activity was 35.1% in TRD, 43.7% in LTRD, 50.4% in ATRD, and 67.5% in BTRD. Study results show that benidipine and tramadol co-treatment is better than co-treatment with lacidipine or amlodipine in achieving minimal toxic effects and maximum analgesia.
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