Publication: Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice
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Sakul, Arzu
Ozansoy, Mehmet
ELİBOL, BİRSEN
Ayla, Sule
Gunal, Mehmet Yalcin
Yozgat, Yasemin
Basaga, Huveyda
Sahin, Kazim
KAZANCIOĞLU, RÜMEYZA
Kilic, Ulkan
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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.
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Sakul A., Ozansoy M., ELİBOL B., Ayla S., Gunal M. Y. , Yozgat Y., Basaga H., Sahin K., KAZANCIOĞLU R., Kilic U., -Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice-, TURKISH JOURNAL OF BIOLOGY, cilt.43, ss.179-188, 2019