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- 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 Erişim2026ATP and Liv-52 Ameliorate Linezolid-Induced Liver Injury via Modulation of NF-κB/NLRP3 Pathways
Cerrah, Serkan; Baykan, Ahmed Ramiz; Sezgin, Esra Tuba; Huseynova, Gulbaniz; Karabacak, Elif; Tanas, Serdar; Baykan, Emine Kartal; Gunay, Murat; Gungor, Ali; Suleyman, Halis
Objective: Linezolid (LZD), an oxazolidinone antibiotic widely used against Gram-positive infections, has been associated with mitochondrial dysfunction and hepatotoxicity, particularly during prolonged use. This study aimed to investigate the protective effects of adenosine triphosphate (ATP) and Liv-52 against LZD-induced liver injury, with a focus on oxidative stress, inflammation, and necroptosis pathways. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control (HG), LZD-treated (LZDG), Liv-52 + LZD (LVLZ), and ATP + LZD (ATLZ). Liv-52 (50 mg/kg, orally) and ATP (5 mg/kg, intraperitoneally) were administered prior to LZD (125 mg/kg, orally) for 14 days. Results: Following LZD administration, malondialdehyde (MDA) levels markedly increased, indicating oxidative stress, while total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) activities significantly decreased. Histopathological examination revealed pronounced hepatocellular damage accompanied by increased NF-κB, NLRP3, RIPK3, and MLKL expression, indicating activation of inflammatory and necroptotic pathways. Treatment with ATP and Liv-52 significantly ameliorated these biochemical, histopathological, and molecular alterations. Conclusions: Treatment with ATP and Liv-52 significantly attenuated oxidative stress, improved histopathological alterations, and suppressed the expression of inflammatory and necroptotic markers. Notably, ATP exhibited a more pronounced protective effect compared to Liv-52. In conclusion, LZD induces hepatotoxicity through oxidative stress-mediated inflammatory and necroptotic mechanisms, while ATP and Liv-52 confer hepatoprotection, with ATP showing superior efficacy.
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 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 - Review ArticleAçık Erişim2025Pathogenesis of Amiodarone-Related Toxicity
Aksakal, Enbiya; Suleyman, Halis; Bulut, Seval
Amiodarone is an antiarrhythmic drug widely used to treat atrial and ventricular arrhythmias. On the other hand, amiodarone can cause toxicity in many organs such as the heart, lungs, gastrointestinal tract, liver, eyes, thyroid, and skin during and after treatment. The tendency of amiodarone to accumulate in organs with a high lipid content increases its half-life and causes prolonged therapeutic and toxic effects. Oxidative stress is thought to be the main factor in amiodarone-induced tissue damage. Amiodarone has been shown to cause oxidative damage through an increase in reactive oxygen species (ROS) and a decrease in aioxidants. Amiodarone also disrupts the mitochondrial respiratory chain and decreases adenosine triphosphate (ATP) levels, which are among the causes of toxicity. Amiodarone has also been shown to increase levels of pro-inflammatory cytokines. The increase in these cytokines may further increase ROS levels and exacerbate the damage. On the other hand, the structural feature of amiodarone has been considered another cause of toxicity, and thyroid damage has been attributed to its similarity to thyroxine and iodine content. Considering the widespread use of amiodarone, toxic effects and prevention of toxicity become more important. Given the significant role of oxidative stress and inflammation in amiodarone-related toxic effects, antioxidant and anti-inflammatory therapies are emerging as promising strategies to mitigate these adverse effects. In addition, studies to maintain cellular ATP levels at physiological levels may emerge as an important treatment strategy to prevent amiodarone toxicity.
RDL Kalıcı Kaydıİncele - Review ArticleAçık Erişim2025The Use of Metyrosine in the Treatment of Pheochromocytoma and Paraganglioma Patients: A Review of the Literature
Suleyman, Halis; Babayeva, Mansura; Çakır, Osman Kağan; Huseynova, Gulbaniz
Metyrosine (α-methyl-parathyrosine) functions as an inhibitor of tyrosine hydroxylase, thereby impeding the conversion of tyrosine to 3,4-dihydroxyphenylalanine. This reaction represents the rate-limiting step in the synthesis of catecholamines. This review examines the mechanisms of metyrosine action and its application for treatment purposes. The published literature was collated from a range of scientific databases, including PubMed, SciFinder, ScienceDirect, Wiley Online Library, Google Scholar and Web of Science. The use of metyrosine has been demonstrated to reduce catecholamine biosynthesis in patients with catecholamine-secreting pheochromocytoma and paraganglioma. The safety and efficacy of metyrosine in the treatment of pheochromocytoma and paraganglioma is substantiated by empirical evidence from studies demonstrating its general tolerability and clinical practice use. Metyrosine has been shown to potentially mitigate the occurrence of surgical complications by enhancing intraoperative hemodynamics. Studies have demonstrated that the administration of metyrosine prior to pheochromocytoma and paraganglioma surgery reduces the risk of hypertensive crisis and severe hypertension, as well as intraoperative haemodynamic variability. It is imperative that further research is conducted to elucidate the pharmacokinetics, intricate molecular mechanisms, and safety profile of methyrone. To this end, the utilization of meticulously designed randomized clinical trials is crucial.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Biochemical and Histopathologic Investigation of the Effect of Rilmenidine on Ovarian Ischemia-Reperfusion Injury in Rats
Yilmaz, Betul Kalkan; Bulut, Seval; Yilmaz, Nesrin; Yucel, Nurinisa; Cicek, Betul; Kadioglu, Berrin Goktug; Bakan, Nuri; Mendil, Ali Sefa; Suleyman, Halis
Background and Objective: Rilmenidine is an antihypertensive drug with sympatholytic properties as well as antioxidative and anti-inflammatory properties. To investigate the biochemical and histopathological effects of Rilmenidine on Ovarian IschemiaReperfusion (I/R) injury in a rat model, this study aims to determine its potential protective role against oxidative stress and tissue damage associated with ovarian IR injury. Materials and Methods: The 24 albino Wistar female rats were divided into four groups: Healthy (HG), sham-operation (SOG),ovarian ischemia-reperfusion (OIRG) and Rilmenidine+ovarian ischemia-reperfusion (ROIRG). Ovaries in SOG, OIRG and ROIRG groups were exposed to ischemia for three hrs, followed by reperfusion for 6 days. The ROIRG rats were treated with Rilmenidine (0.2 mg/kg) daily for 6 days before ischemia. The ovaries were analyzed for oxidant, antioxidant and proinflammatory cytokines and examined histopathologically. Statistical analysis was performed using one-way ANOVA and Kruskal-Wallis tests (p<0.05). Results: The IR procedure increased tissue malondialdehyde, tumor necrosis factor-a, interleukin-6 and interleukin-1$ levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). Severe histopathologic damage and 8-hydroxy-20deoxyguanosine immunopositivity were also observed in ovarian tissues ofOIRG (p<0.001). Rilmenidine inhibited IR-related biochemical, histopathological and immunohistochemical abnormalities (p<0.05). Conclusion: Rilmenidine may be an efficient therapeutic strategy for the protection from ovarian IR injury.
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 - 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 - ArticleAçık Erişim2025Myricetin protects against doxorubicin-induced acute kidney injury in rats by mitigating oxidative damage and apoptotic response
Karadogan, Muhammed Talha; Cicek, Betul; Cinisli, Kagan Tolga; Mendil, Ali Sefa; Ozkaraca, Mustafa; Yilmaz, Furkan; Suleyman, Halis
Introduction: Doxorubicin (DOX) is a potent anti-neoplastic agent widely preferred in treating various tumors. However, DOX’s off-target toxicity in healthy tissues, such as nephrotoxicity, limits its clinical utilization. DOX generates oxidative stress and apoptosis in the kidneys, which stimulates cytotoxic cellular signaling. Myricetin (MYC), an important natural flavonoid, exhibits antioxidant and antiapoptotic features. In this regard, the current report was designed to explore the renoprotective potential of MYC on DOX-induced nephrotoxicity. Methods: Animals were divided into four groups with six rats in each group: control, MYC, DOX, MYC + DOX. MYC was given orally to rats at 100 mg/kg for 10 days and DOX was injected intraperitoneally as a single dose of 20 mg/kg on the eighth day. Serum samples were evaluated for creatinine and blood urea nitrogen (BUN), and histopathological analysis of the kidneys was conducted. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the renal tissues. Additionally, biochemical assessments of Bax and Bcl-2 proteins, along with immunohistochemical evaluations of the expression levels of caspase-3 and apoptosis-inducing factor (AIF), were conducted to evaluate apoptosis. Results: Pre-treatment of MYC decreased DOX-elicited elevation in creatinine and BUN levels (p < 0.05). Histopathological findings demonstrated the nephroprotective role of MYC on renal damage (p < 0.05), which was in harmony with the biochemical findings. Furthermore, MYC demonstrated antioxidant properties by reversing the increase in MDA, TOS, and MPO levels and the decrease in GSH, GPx, and TAS levels caused by DOX (p < 0.05). MYC pre-treatment also markedly prohibited DOX-induced elevation of Bax level, and rise of expression of caspase-3 and AIF, and reduction of Bcl-2 levels (p < 0.05). Conclusion: It could be supposed that the nephroprotective role of MYC towards DOX-induced kidney damage might be mediated by its antioxidant and antiapoptotic features.
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 - ArticleAçık Erişim2025Sunitinib’s Effect on Bilateral Optic Nerve Damage in Rats Following the Unilateral Clamping and Unclamping of the Common Carotid Artery
Cicek, Ibrahim; Esenulku, Cenap Mahmut; Somuncu, Ahmet Mehmet; Bulut, Seval; Yucel, Nurinisa; Bal Tastan, Tugba; Coban, Taha Abdulkadir; Suleyman, Halis
Background/objectives: Common carotid artery occlusion can cause oxidant and inflammatory damage to the optic nerve. In this study, the effect of sunitinib was investigated, the antioxidant and anti-inflammatory properties of which have been previously reported and shown to be protective in I/R injury and in preventing bilateral optic nerve ischemia–reperfusion (I/R) injuries after unilateral common carotid artery ligation in rats. Methods: In this study, 18 Albino Wistar male rats were divided into SG (sham-operated), CCU (clamping and unclamping), and SCCU (sunitinib + clamping and unclamping) groups. One hour before the surgical procedures, sunitinib (25 mg/kg, oral) was given to SCCU rats. Anesthesia was induced with ketamine (60 mg/kg, ip) and sevoflurane. The right common carotid arteries of all rats were accessed under anesthesia. While the skin opened in SG rats was closed with sutures, the right common carotid arteries of CCU and SCCU rats were clipped, and an ischemia period was created for 10 min. Then, reperfusion (6 h) was achieved by unclipping. After euthanasia with ketamine (120 mg/kg, intraperitoneally), the right and left optic nerves of the rats were removed and examined biochemically and histopathologically. Results: Malondialdehyde, tumor necrosis factor α, interleukin-1β, and interleukin-6 were increased, and total glutathione levels had decreased in both ipsilateral and contralateral optic nerves (p < 0.05). These changes were more prominent on the ipsilateral side. Similarly, histopathological damage was observed to be more on the ipsilateral side (p < 0.05). Biochemical and histopathological changes were significantly suppressed in rats receiving sunitinib treatment (p < 0.05). Conclusions: Sunitinib may protect optic nerve tissue against I/R injury by reducing oxidative stress and inflammation.
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 Erişim2025Protective effect of adenosine triphosphate against cisplatin-induced necrotic and degenerative oral mucositis in rats
Salcan, Ismail; Dilber, Muhammed; Suleyman, Zeynep; Yucel, Nurinisa; Salcan, Sara; Kesan, Sefa; Yazici, Gulce Naz; Celik, Fatih; Koseturk, Merve; Alp, Nurdan Alcan
Inflammation, oxidative damage, and adenosine triphosphate (ATP) depletion play a role in the7 pathogenesis of cisplatin (CIS)-induced oral mucositis. Objective: The purpose of this research is to examine8 the impact of ATP against potential oral mucositis development in cisplatin-treated rats. Methodology All rats9 were randomly assigned to four groups, namely healthy control group (HG), ATP group (ATPG), Cisplatin10 group (CISG), and ATP + Cisplatin group (ATCS). Firstly, ATP 4 mg/kg was administered via intraperitoneal11 injection (IP) to both ATPG and ATCS groups. The same volume of normal saline was injected into HG and12 CISG groups. After 1 h, cisplatin 5 mg/kg was administered via IP to CISG and ATCS groups. The drugs13 were taken 1x1 for 7 d. Later, tongue tissues were collected from all groups. Biochemical, macroscopic,14 and histopathological examinations were performed on all tissues. Results: ATP inhibited cisplatin-induced15 oxidative damage and pro-inflammatory cytokines levels in tongue tissue. In the CIS group, a significant16 number of distinct sulcus formations were found in the apex and corpus, as well as a few ulcer foci in the17 corpus, significant papilla loss, and bleeding. Meanwhile, in the ATP group, a similar appearance to healthy18 tissue was observed. Histopathologically, it was determined that in cisplatin-aggravated tongue tissue19 damage, filiform papillae decreased when ATP was administered, and the arrangement and structures of20 the epithelium, blood capillaries, muscle groups, and adipose cell groups were normal. Conclusions: Oral21 mucositis caused by cisplatin is alleviated by ATP. These findings may be useful for developing new therapeutic22 approaches to prevent or treat mucositis, a side effect so severe that can lead to treatment discontinuation.23 24.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Effect of adenosine triphosphate on methylphenidate-induced oxidative and inflammatory kidney damage in rats
Yeter, Bahtinur; Suleyman, Zeynep; Bulut, Seval; Cicek, Betul; Coban, Taha Abdulkadir; Demir, Ozlem; Suleyman, Halis
The purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied via oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Association of Tramadol-Induced Ovarian Damage and Reproductive Dysfunction with Adenosine Triphosphate and the Protective Role of Exogenous ATP Treatment
Gumusburun, Neset; Delibasi, Ilhan Bahri; Bulut, Seval; Suleyman, Halis; Kalkan Yilmaz, Betul; Coban, Taha Abdulkadir; Mendil, Ali Sefa; Suleyman, Zeynep
Background: Tramadol, a weak opioid analgesic agent, is known to induce ovarian damage. Previous studies have held oxidative stress responsible for the adverse effects of tramadol on female reproduction. This study examined the protective effects of ATP against tramadol-induced ovarian damage and reproductive dysfunction in rats. Methods: Rats were divided into four groups (n = 12); healthy (HG), only ATP (ATPG), only tramadol (TMDG), and ATP + tramadol (ATMG). ATP was injected intraperitoneally at 25 mg/kg. Tramadol at 50 mg/kg was initiated one hour after ATP. The treatment was administered once a day for 14 days. Six rats from each group were euthanized. For two months, the remaining rats were paired with male rats. Rats that failed to give birth during this period were considered infertile. A maternity period was calculated for the rats that were delivered. Results: Tramadol caused an increase in malondialdehyde and interleukin-6, and decreased total glutathione, superoxide dismutase, and catalase levels in the ovarian tissue. Furthermore, tramadol disrupted the histological structure of the ovaries, and immunohistochemical staining revealed severe immunopositivity. Tramadol again caused infertility and delayed pregnancy in fertile women. By suppressing biochemical changes, ATP significantly reduced tramadol-induced ovarian damage. Both histopathologically and immunohistochemically, ATP treatment regressed ovarian damage. Additionally, ATP significantly reduced tramadol-induced infertility and maternal delay. Conclusions: The results indicate that tramadol-induced oxidative and inflammatory ovarian injury, infertility, and caspase 3 were suppressed by ATP, as demonstrated by our experimental findings.
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 - 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.
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