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

Abstract

The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneysthat lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to copewith nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squaleneagainst 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 wereinvestigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in additionto histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-γ) decreased in the cisplatin andsqualene 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 reversedby squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney