Therapeutic effects of thymoquinone in doxorubicin-induced hepatotoxicity via oxidative stress,inflammation and apoptosis |
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Authors: | Ali Tuğrul Akin Emel Öztürk Emin Kaymak Derya Karabulut Birkan Yakan |
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Affiliation: | 1. Department of Biology, Science Faculty, Erciyes University, Kayseri, Turkey;2. Histology-Embryology Department, Faculty of Medicine, Harran University, Sanliurfa, Turkey;3. Histology-Embryology Department, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey;4. Histology-Embryology Department, Faculty of Medicine, Erciyes University, Kayseri, Turkey |
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Abstract: | Cancer is a lethal disease that is characterized by uncontrolled cell division and proliferation, and it results in death in many organisms. Doxorubicin (DOX) is a therapeutic agent used for treatment of many cancer types, but it induces serious hepatotoxicity. In this study, we aimed to determine possible hepato-therapeutic effects of thymoquinone (THQ) on DOX-induced hepatotoxicity in rats. Rats were divided into five groups (n = 8): Control, THQ (10 mg/kg/day/i.p for 14 days), Olive Oil (equal volume with THQ for 14 days), DOX (single dose, 15 mg/kg/i.p on 7th day) and DOX + THQ (10 mg/kg/day/i.p and DOX 15 mg/kg/i.p on 7th day). At the end of the experiment, liver tissues were extracted and evaluated histopathologically. eNOS, iNOS and Cas-3 immunostaining were performed to determine the expression levels. TUNEL method was used to determine apoptotic index. Furthermore, liver tissue total antioxidant status (TAS), total oxidant status (TOS), TNF-α and TGF-β levels were measured by ELISA assay. The DOX group showed histopathological deterioration compared to Control group. Moreover, apoptotic index, eNOS, iNOS and Cas-3 expressions increased in DOX group. While TAS level of the DOX group decreased, TOS level increased. TNF-α and TGF-β levels increased in DOX group. However, there was improvement in DOX + THQ group compared to DOX group. Moreover, apoptotic cell number, eNOS, iNOS and Cas-3 expressions decreased in DOX + THQ group compared to DOX group. We concluded that thymoquinone can be used as a phytotherapeutic for reducing DOX-induced liver damage. |
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Keywords: | apoptosis doxorubicin inflammation oxidative stress thymoquinone |
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