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- 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 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 - 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 - 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 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 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 - 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 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 - 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 - ArticleYalnız künye2025Effects of adenosine triphosphate and coenzyme Q10 on potential hydroxychloroquine-induced retinal damage in rats.
Ozbay, Ahmet Duhan; Somuncu, Ahmet Mehmet; Cicek, Ibrahim; Yavuzer, Bulent; Bulut, Seval; Huseynova, Gulbaniz; Tastan, Tugba Bal; Gulaboglu, Mine; Suleyman, Halis
This study aimed to investigate biochemically and histopathologically the protective effect of adenosine triphosphate (ATP) and coenzyme Q10 (CoQ10) against potential hydroxychloroquine (HCQ)-induced retinal damage in rats. Twenty-four male albino Wistar-type rats were randomly separated into four groups: healthy (HG), receiving HCQ (HQG), receiving ATP + HCQ (AHQ), and receiving CoQ10 + HCQ (CoQHQ). ATP (4 mg/kg, intraperitoneal) was given to the AHQ, and CoQ10 (10 mg/kg, oral) to the CoQHQ. Rats in the HQG, AHQ, and CoQHQ were given HCQ (120 mg/kg, oral) 1 h after administering ATP and CoQ10. Treatments continued once a day for seven days. On the 8th day, the rats were sacrificed with 50 mg/kg sodium thiopental, and the eyes were removed. Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT), and interleukin-6 (IL-6) levels were measured in the retrieved eye tissues and retinal tissues were assessed histopathologically. An increase in MDA and IL-6 levels and a decrease in tGSH, SOD, and CAT levels were detected in the eye tissues of the HQGcompared to the HG. HCQ-induced changes in oxidant and antioxidant levels were significantly suppressed by ATP and CoQ10 treatment. ATP was more successful than CoQ10 in this inhibition. Severe damage was observed in the eye tissues of the HQG group, whereas the damage was mild in the AHQ and moderate in the CoQHQ. Although both ATP and CoQ10 have the potential to be effective in the prevention of HCQ-induced retinal damage through antioxidative activity, ATP appears to be the more preferable treatment approach.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Revealing the protective potential of D-(-)-Quinic acid against thioacetamide-induced hepatic encephalopathy in rats
Ciftel, Sedat; Cicek, Betul; Bolat, Ismail; Bulut, Seval; Yildirim, Serkan; Suleyman, Bahadir; Qaniyev, Musa; Süleyman, Halis
The objective of this study was to elucidate the impact of D-(-)-Quinic acid (D-(-)-QA), a natural phenolic acid, on the molecular mechanisms of inflammation and oxidative stress in brain and liver damage in thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats. To establish an experimental HE model, rats were injected with three doses (200 mg/kg, intraperitoneally) of TAA every other day, followed by the administration of D-(-)- QA (200 or 400 mg/kg, orally) for fourteen days. Serum ammonia, alanine transaminase (ALT), and aspartate transaminase (AST) levels were detected. Tumor necrosis factor (TNF-α), interleukin-1beta IL-1β, and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were analyzed to assess inflammation and oxidative damage in brain and liver tissues. Histopathological examinations, immunofluorescence (PI3K and AKT expressions), and immunohistochemical (HSP70 expression) examinations were also performed. TAA administration causedhyperammonemia and increased ALT and AST levels, along with histopathological changes indicating damage to hepatocytes and neurons. Additionally, it disrupted the inflammatory response and promoted oxidative damage by activating the PI3K/AKT-related HSP70 response in the brain and liver. Treatment with D-(-)-QA significantly prevented the increase in ammonia levels and improved the liver function. In addition, the increase in TNF-α, and IL-1β, proinflammatory cytokines in liver and brain tissues as well as the increase in MDA and decrease in SOD and GSH were significantly suppressed by D-(-)-QA. By suppressing HSP70 and PI3K/AKT signaling in brain and liver tissues, D-(-)-QA administration attenuated inflammation and oxidative damage. D-(-)-QA may be an alternative to current clinical interventions by inhibiting inflammation and oxidative damage signaling toward the pathogenesis of HE.
RDL Kalıcı Kaydıİncele - 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 - ArticleAçık Erişim2024Comparative Investigation of the Effects of Adenosine Triphosphate and Agomelatine Against Acrolein-Induced Oxidative and Inflammatory Lung Injury in Rats
Unver, Edhem; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Background and Objective: Acrolein-induced tissue damage has been attributed to oxidative stress and inflammation.This study aimed to determine the effects of adenosine triphosphate (ATP) and agomelatine, two substances known to have antioxidant and antiinflammatory effects, separately and in combination, on possible acrolein-induced lung damage in rats. Materials and Methods: There were 30 albino Wistar rats divided into five groups of six: Healthy (HG), acrolein (AC), ATP+acrolein (ATAC), agomelatine+acrolein (AGAC) and ATP+agomelatine+acrolein (AAAC). The dose of ATP administered intraperitoneally was 4 mg/kg and the dose of agomelatine administered orally was 25 mg/kg. An oral dose of acrolein 3 mg/kg was given 1 hr following the administration of ATP and agomelatine. For 30 days, the treatment protocol was followed once a day. Afterwards, the rats were euthanized and their lungs were removed. Oxidants, antioxidants and pro-inflammatory cytokines were measured in lung tissues. Results: In lung tissues, acrolein increased malondialdehyde, nuclear factor kappa, tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). The ATP+agomelatine, ATP and agomelatine treatments were the most effective at preventing these biochemical changes, respectively (p<0.001). As a result, the biochemical data of the HG and AAAC groups were similar (p>0.05). Conclusion: It could be suggested that both ATP and agomelatine might be effective against the pneumotoxic effects of acrolein, though a combination therapy would be more effective.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats
Ulug, Pasa; Nayki, Umit; Mammadov, Renad; Bulut, Seval; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Suleyman, Halis
Background: It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. Methods: Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. Results: The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). Conclusion: Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.
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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