Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice

Authors : Arzu SAKUL, Mehmet OZANSOY, Birsen ELİBOL, Mehmet Yalçın GÜNAL, Yasemin YOZGAT, Hüveyda BAŞAĞA, Kazım ŞAHİN, Rümeyza KAZANCIOĞLU, Ülkan KILIÇ

Pages : 179-188

View : 15 | Download : 5

Publication Date : 2019-12-01

Article Type : Research Paper

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 insert ignore into journalissuearticles values(7 mg/kg); was given to male Balb/c mice. Squalene insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(OSI);, inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(AKT);. Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin insert ignore into journalissuearticles values(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.
Keywords : AKT, cisplatin induced nephrotoxicity, mice, mTOR, oxidative stress, squalene