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Oleanolic acid attenuates cisplatin-induced nephrotoxicity in mice and chemosensitizes human cancer cells to cisplatin cytotoxicity

Oleanolic acid (OA) is a natural triterpenoid that possesses beneficial health effects such as antioxidant, anti-inflammatory, and anti-apoptotic activities. We investigated the therapeutic effect of OA (10 and 40 mg/kg) on cisplatin (CP)-induced (13 mg/kg) nephrotoxicity. Treatment with OA 40 mg/kg once daily for 2 days, 48 h after CP- intoxication, ameliorated the increased serum markers and histological features of kidney injury. Also, CP administration increased renal expression of HO-1 and 4-HNE as well as the expression of TNF-α and NF-κB, which was reduced by OA, indicating the inhibition of oxidative stress and inflammation. Increased expression of caspase-3/9 with a concomitant increase in PARP cleavage, which suggested CP-induced apoptosis in the kidneys, was inhibited by OA. Treatment with OA also ameliorated LC3B-II and Atg5 expression induced by CP, indicating the anti-autophagic activity of OA in the kidneys. Interestingly, OA increased CP cytotoxicity in HeLa cancer cells by inducing autophagic cell death. The chemosensitization of HeLa cells to CP suggests an additional beneficial effect of OA in cervical cancer patients due to reduced CP dosage requirements.

oleanolic acid ; colon cancer ; apoptosis ; autophagy ; mitophagy, 5-fluorouracil

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