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    Ameliorating effects of tempol on methotrexate-induced liver injury in rats
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2018) Pinar, Neslihan; Kaplan, Mahir; Ozgur, Tumay; Ozcan, Oguzhan
    Methotrexate (MTX) is used in the treatment of certain types of cancers and chronic inflammatory illnesses, although the clinical use of MTX is limited due to its adverse effects, the most common of which are hepatotoxicity and nephrotoxicity. In the present study, we demonstrate the protecting influence of tempol related to oxidative stress in MTX-induced liver toxicity in rats using histopathological and biochemical parameters. The rats were divided into four groups: control group (group 1), tempol group (group 2), MTX group (group 3) and MTX + tempol group (group 4). The control group (group 1) received physiological saline for 10 days; the tempol group (group 2) received 30 mg/kg i.p. for 10 days, the MTX group (group 3) received a single dose of 20 mg/kg intraperitoneal (i.p.) on the fourth day of the study, and the MTX + tempol group (group 4) received a single dose of 20 mg/kg i.p. on the fourth day, followed by tempol 30 mg/kg i.p. for 10 days. Malondialdehyde (MDA), myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were found to be significantly lower in the MTX + tempol group then in the MTX group; while superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were found to be higher in the MTX + tempol group than in the MTX group. Tempol ameliorates vacuolic degeneration, inflammation and necrosis in MTX-treated rats. Our study demonstrates that tempol treatment after MTX administration ameliorates oxidative damage in liver tissue in rats.
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    Protective effect of alpha lipoic acid on cisplatin induced hepatotoxicity in rats
    (Taylor & Francis Ltd, 2020) Pinar, Neslihan; Cakirca, Gokhan; Hakverdi, Sibel; Kaplan, Mahir
    We investigated the protective effect of alpha lipoic acid (ALA) against cisplatin (CIS) induced hepatotoxicity in rats. ALA is an antioxidant and anti-inflammatory agent that exhibits free radical scavenger properties and direct antioxidant effects on recycling of other cellular antioxidants. We used four equal groups of rats. The control group: saline solution (0.9%) was administered intraperitoneally (i.p.); ALA group: administered a single dose 100 mg/kg ALA i.p. for 10 days; CIS group was administered a single dose 5 mg/kg CIS i.p. on the first day of the study; CIS + ALA group was administered a single dose 5 mg/kg CIS i.p. on the first day of study, then 100 mg/kg ALA i.p. for 10 days. In the CIS group, Bax, caspase3, malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were increased, whereas Bcl-2, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were decreased compared to the control group. In the CIS + ALA group, Bax, caspase 3, MDA, AST and ALT levels were decreased, whereas Bcl-2, SOD, CAT and GPx levels were increased compared to the CIS group. In the CIS group we found intense perivenule sinusoid dilation, karyomegaly, pyknotic and karyolytic cells, central vein congestion, parenchymal inflammation, mild bile duct proliferation and periportal sinusoid dilation. Histological liver damage was reduced in the CIS + ALA group. ALA may useful for treating CIS induced hepatotoxicity owing to its antioxidant and anti-inflammatory effects.
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    Protective effect of dexpanthenol on cisplatin induced nephrotoxicity in rats
    (Taylor & Francis Ltd, 2022) Pinar, Neslihan; Topaloglu, Meyli; Secinti, Ilke Evrim; Buyuk, Esra; Kaplan, Mahir
    Cisplatin (CIS) is an antineoplastic agent used for treating solid organ tumors. Toxic side effects of CIS treatment include nephrotoxicity, neurotoxicity, ototoxicity, myelosuppression and hepatotoxicity. Dexpanthenol (DEX) exhibits antioxidant and anti-inflammatory effects and protective effects against free oxygen radicals. We investigated the protective effects of DEX on CIS induced nephrotoxicity. Animals were divided into four groups of 10. The control group was given saline. The DEX group was treated with DEX for 10 days. The CIS group was treated with a single dose of CIS. The DEX + CIS group was given a single dose of CIS followed by DEX for 10 days. We found increased levels of malondialdehyde (MDA), blood urea nitrogen (BUN) and creatinine, while superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO) levels were decreased in the CIS group. MDA, BUN and creatinine levels were decreased, while SOD, CAT, GPx and MPO levels were increased in the DEX + CIS group. Renal tubule damage, inflammation and histopathology scores were significantly higher in the CIS group than the control. The DEX + CIS group exhibited less renal tubule damage and inflammation, and lower histopathological assessment scores than the CIS group. Significant cortical tubule damage and interstitial inflammation were observed in the CIS group. Tubule damage was slightly less, and mild tubule dilation and less cast formation were observed in the DEX + CIS group; also, inflammation was less severe than for the CIS group. DEX may have therapeutic potential for treating CIS induced nephrotoxicity due to its antioxidant and anti-inflammatory properties.
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    The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2018) Pinar, Neslihan; Cakirca, Gokhan; Ozgur, Tumay; Kaplan, Mahir
    Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously, chemotherapeutic agents have been reported to cause permanent azoospermia and infertility in men. Methotrexate has been also shown to damage the seminiferous tubules of the testicles, lower the sperm count, and cause genetic mutations (in DNA) in sperm. In this study, we aimed to investigate the protective effects of alpha lipoic acid (ALA) on MTX-induced testicle damage in a rat model. A total of 40 male Wistar Albino rats were used in this study. The rats were divided into four groups including 10 rats in each. The first group (control group) received only saline intraperitoneal (i.p.); the second group (ALA group) was given ALA 100 mg/kg i.p.; the third group (MTX group) received single dose MTX 20 mg/kg i.p.; and the fourth group (MTX+ALA group) received single dose MTX 20 mg/kg i.p. and ALA 100 mg/kg i.p. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) levels in the testicular tissue and serum testosterone, serum total antioxidant status (TAS) and total oxidant status (TOS) levels were biochemically evaluated. Testicular tissues histopathologically evaluated. In the MTX group, the MDA, TAS and TOS levels were higher, while the SOD, CAT, GPx, MPO and serum testosterone levels decreased. Compared to the MTX group, the MDA, TAS and TOS levels were lower and the SOD, CAT, GPx, MPO and serum testosterone levels increased in the MTX+ALA group. In the histopathological examination, the mean seminiferous tubule length (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were found to significantly decrease in the MTX group, compared to the control group. These values were significantly higher in the MTX+ ALA group, compared to the MTX group (p < 0.05). In our experimental study, MTX caused severe tissue destruction in testicles by increasing the formation of free oxygen radicals. Based on our study results, we suggest that, as a potent free radical scavenger, ALA can reduce MTX-induced testicular tissue damage thanks to its antioxidant and anti-inflammatory properties.