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

Abstract Oleanolic acid (OA) is a natural triterpenoid that possesses numerous beneficial health effects such as antioxidant, anti-inflammatory and anti-apoptotic activities. In this study, 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. CP administration increased renal expression of antioxidant and anti-inflammatory markers, which was reduced by OA. The increase in proapoptotic caspase-3 and -9 activations, with concomitant increase in poly (ADP-ribose) polymerase (PARP) cleavage, were dose-dependently inhibited by OA. Treatment with OA also ameliorated microtubule-associated protein 1A/1B-light chain 3B (LC3B)-II and autophagy-related protein (Atg) 5 expression induced by CP. The suppression of CP-induced oxidative stress, apoptosis, autophagy and inflammatory response by OA coincided with the inhibition of extracellular-regulated kinase (ERK) 1/2, signal transducer and activator of transcription (STAT) 3 and nuclear factor-kappa B (NF-κB). Interestingly, OA increased CP cytotoxicity in HeLa cervical cancer cells by inducing cytotoxic autophagy. The chemosensitization of HeLa cells to CP suggests a potential beneficial effect of OA in cervical cancer patients due to reduced CP dosage requirements, which requires further investigation.