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    Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats
    (Taylor & Francis Ltd, 2022) Aktas, Ibrahim; Gur, Fatih Mehmet
    We investigated the hepato-protective effects of thymoquinone (TQ) and beta-aminoisobutyric acid (BAIBA). We used five groups of 8-week-old male rats: untreated control group, streptozotocin (STZ) diabetic group, STZ + TQ group, STZ + BAIBA group, and STZ + TQ + BAIBA group. After experimental diabetes mellitus (DM) was established using STZ, TQ was given to the STZ + TQ group, BAIBA to the STZ + BAIBA group, and TQ and BAIBA to the STZ + TQ + BAIBA group. In the STZ group, body weight, relative liver weight, and glutathione, blood albumin and insulin levels were decreased compared to the control. Also, water and food consumption, tumor necrosis factor-alpha expression, malondialdehyde, blood glucose, alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase levels were increased the STZ group compared to the control group. In the STZ group, sinusoid congestion and dilation, monocyte and lymphocyte infiltration and microvesicular steatosis were observed in the liver tissue. Pathological changes caused by DM were reduced significantly in the STZ + TQ, STZ + BAIBA and STZ + TQ + BAIBA groups. The protective effect of BAIBA was greater than for TQ; the greatest protective effect was observed following combined use of TQ + BAIBA. We suggest that our findings for the STZ + TQ, STZ + BAIBA and STZ + TQ + BAIBA groups were due to the antioxidant effects of TQ and BAIBA. TQ and BAIBA appear to be potential therapeutic agents for ameliorating hepatic damage due to DM.
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    Investigation of the protective and therapeutic effects of ?-aminoisobutyric acid (BAIBA) and Thymoquinone in the diabetic nephropathy
    (Ms-Editions, 2021) Aktas, Ibrahim; Gur, Fatih Mehmet
    In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and beta-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney v.:iglu, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-alpha) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.
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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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    The ameliorative effects of thymoquinone and beta-aminoisobutyric acid on streptozotocin-induced diabetic cardiomyopathy
    (Churchill Livingstone, 2021) Gur, Fatih Mehmet; Aktas, Ibrahim
    Diabetic cardiomyopathy (DCM) is a cardiac dysfunction observed in a patient with diabetes that may lead to heart failure. No specific treatment has yet been tested in DCM. Therefore, in this study, it was investigated that the potential of thymoquinone (TYM) and beta-aminoisobutyric acid (BAIBA) to treat DCM. Five groups (n = 7) were formed, namely control, diabetes, TYM, BAIBA and TYM + BAIBA, with a random selection from 35 adult male rats. Diabetes mellitus was induced by intraperitoneal administration of 50 mg/kg streptozotocin to all groups except the control. After establishing experimental diabetes, TYM (20 mg/kg/day) and BAIBA (100 mg/kg/day) were administered alone or in combination with other groups other than the control and diabetes groups for five weeks by gavage. Serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, and tissue malondialdehyde levels increased significantly, and tissue glutathione levels decreased in the diabetes group compared to the control group. An increase in the expression of tumor necrosis factor-alpha in the myocardium and the rate of fibrosis and apoptosis were found in the histopathological analysis. In the TYM and BAIBA groups, all pathological changes observed in the diabetes group improved significantly. The therapeutic effects of these agents on DCM are probably due to their antihyperglycemic, antidiabetic, antioxidant, and anti-inflammatory effects. The present results suggested that TYM and BAIBA have the potential therapeutic effects on DCM that were used alone or combined.