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

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Sakul A., Ozansoy M., ELİBOL B., Ayla S., Gunal M. Y., Yozgat Y., ...More

TURKISH JOURNAL OF BIOLOGY, vol.43, no.3, pp.179-188, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 43 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.3906/biy-1902-77
  • Journal Name: TURKISH JOURNAL OF BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.179-188
  • Keywords: AKT, cisplatin-induced nephrotoxicity, mice, mTOR, oxidative-stress, squalene, OLIVE OIL, INDUCED NEPHROTOXICITY, SIGNALING PATHWAY, CANCER-RISK, IN-VIVO, PROTECTION, ANTIOXIDANT, MECHANISMS, TOXICITY, PLASMA
  • Bezmialem Vakıf University Affiliated: Yes

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-gamma) 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.