Turkish Journal of Biology
Abstract
The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-γ) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.
DOI
10.3906/biy-1902-77
Keywords
AKT, cisplatin-induced nephrotoxicity, mice, mTOR, oxidative-stress, squalene
First Page
179
Last Page
188
Recommended Citation
ŞAKUL, A. A, OZANSOY, M, ELİBOL, B, AYLA, Ş, GÜNAL, M. Y, YOZGAT, Y, BAŞAĞA, S. H, ŞAHİN, K, KAZANCIOĞLU, R, & KILIÇ, Ü (2019). Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice. Turkish Journal of Biology 43 (3): 179-188. https://doi.org/10.3906/biy-1902-77