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    A synthetic prostaglandin E1 analogue, misoprostol, ameliorates paclitaxel-induced oxidative damage in rat brain
    (Elsevier Science Inc, 2022) Gur, Fatih Mehmet; Bilgic, Sedat
    The main objective of our study was to examine the protection of misoprostol (MP) on paclitaxel (PAX) side effects in rat brains. Twenty-eight female Sprague-Dawley rats were provided to form 4 groups, each containing seven rats: the control group was given 1 mL of 0.9% NaCl intraperitoneally (i.p.) and 1 mL of 0.9% NaCl orally for six days. In treatment groups, each rat was injected with 2 mg/kg PAX i.p. on days 0, 2, 4, and 6 of the study, and 0.2 mg/kg/day MP was given by oral gavage for six days. Levels of malondialdehyde (MDA) and glutathione (GSH), activities of superoxide dismutase (SOD), and catalase (CAT) of tissue samples were measured. In immunohistochemical analyzes, it was observed that tumor necrosis factor-alpha (TNF-alpha) and cleaved caspase-3 expression in the cerebellum hippocampus and cerebral cortex were increased in the PAX group compared to the other groups. The increase in TNF-alpha and cleaved caspase-3 expression detected in PAX group rats were significantly decreased in the PAX + MP group. The results obtained in this study confirm the hypotheses that PAX can increase apoptosis in brain tissue both directly and through cytokines such as TNF-alpha. It also shows that MP can be used as a protective and therapeutic pharmacological agent against the harmful effects of PAX on brain tissue. In addition, it seems that the use of MP can improve PAX-induced brain damage by preventing oxidative damage.
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    Misoprostol alleviates paclitaxel-induced liver damage through its antioxidant and anti-apoptotic effects
    (Korean Society Toxicogenomics & Toxicoproteomics-Kstt, 2022) Gur, Fatih Mehmet; Aktas, Ibrahim; Bilgic, Sedat; Pekince, Merve
    Backgrounds Anticancer drugs may damage non-target cells and tissues. One of the biggest reasons for changing or stopping chemotherapy regimens is these adverse effects. Objective This study aimed to investigate the therapeutic and protective efficacy of misoprostol (MP) against the harmful effects of paclitaxel (PAX), an anticancer drug, on normal liver tissue. Results Biochemical examinations revealed that activities of serum aspartate aminotransferase, alanine aminotransferase, and levels of triglyceride, and cholesterol and levels of tissue malondialdehyde increased significantly in the PAX group compared to the control group, and glutathione level decreased. The histological structure of the liver tissue of the control group rats was normal. Histopathological changes, such as focal microvesicular steatosis, sinusoidal dilatation, mononuclear cell infiltration, Councilman bodies, and an increase in apoptosis, were also observed in PAX group. The histopathological changes observed in the PAX group were greatly improved in the PAX + MP group. Conclusion When the obtained data were evaluated, it was concluded that the combined use of PAX with MP could reduce the cytotoxic effects of PAX on normal liver tissue, allowing cancer treatment to be continued uninterrupted and effectively.
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    Protective effect of misoprostol against paclitaxel-induced cardiac damage in rats
    (Elsevier Science Inc, 2024) Aktas, Ibrahim; Gur, Fatih Mehmet; Bilgic, Sedat
    Objective: One of the most critical reasons for limiting cancer treatment is the toxic effects of anti-cancer drugs on healthy tissues and organs. This study aims to investigate the possible protective effects of misoprostol (MS) against the damage that arises from paclitaxel (PT), an anti-cancer pharmacological agent, in the rat heart using histopathological and biochemical analyses. Methods: In this study, four groups, each containing seven animals, were formed by random selection from 28 Sprague Dawley female rats. Control group rats were administered 1 ml of normal saline orally and intrapertoneally (i.p.) for six days. While the PT group rats were administered PT at a dose of 2 mg/kg intraperitoneally (i.p.) on days 0, 2, 4, and 6, the MS group was administered MS at a dose of 0.2 mg/kg in 1 ml normal saline by oral gavage for six days. PT and MS were administered to the PT +MS group rats in the same dose and route as the previous groups. Results: Administration of PT increased serum lactate dehydrogenase (LDH), cardiac troponin I (cTn-I), creatine kinase isoenzyme MB (CK-MB), and brain natriuretic peptide (BNP) levels. PT administration also decreased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the heart tissue while increasing the level of malondialdehyde (MDA) (p <0.05). In histopathological examinations, pathological changes, such as edema, congestion, hemorrhage, apoptosis, and degeneration, occurred in the heart tissue of PT-treated rats. The negative changes in histopathological and biochemical parameters that occurred in the PT group were almost not observed in the PT +MS group (p <0.005). Conclusion: When the findings were evaluated, it was concluded that MS protects the heart tissue from the harmful effects of PT, probably due to its antioxidant, anti-apoptotic and TNF-alpha suppressive effects.
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    Protective effects of silymarin against paclitaxel-induced cardiac toxicity
    (Ms-Editions, 2024) Aktas, Ibrahim; Gur, Fatih Mehmet; Martinez, Jose L.; Bilgic, Sedat; Korkoca, Hanifi
    In this study, the protectivity of silymarin (SY) against the harmful effects of paclitaxel (PX) on the heart was investigated. PX was administered 2 mg/kg intraperitoneally to the PX group, 100 mg/kg SY was administered by gavage to the SY group, and both drugs were administered to the PX + SY group as other groups. Treatment with SY significantly decreased cardiac troponin I (cTn-I), brain natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH) levels. In the PX group; the decrease in glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) levels and the increase in malondialdehyde (MDA) levels were significantly normalized with SY administration. Histologically; heart injury was significantly reduced in the PX + SY group compared to the PX group. As a result, it was determined that SY, which has antioxidant, anti-apoptotic and anti-inflammatory effects, could protect the heart tissue from the toxic effects of PX.
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    Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel
    (Churchill Livingstone, 2023) Gur, Fatih Mehmet; Bilgic, Sedat
    One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-a), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group.The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNFa suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively.