Abstract

• Diclofenac induces acute-liver damage causing oxidative stress by mitochondrial dysfunction. • Opuntia extracts prophylactically protect against diclofenac-induced acute liver toxicity. • The protective effect of Opuntia extracts is related to their antioxidant properties to prevent cell dysfunction and death. • Antioxidant activity of Opuntia extracts is due to their biocomponents content such as betacyanins. This study aimed to investigate whether Opuntia spp- extracts protect against diclofenac (DF)-induced hepatotoxicity. Rats were pretreated with Opuntia extracts, betanin (Bet) and N-acetylcysteine (NAC) followed by a single challenge of diclofenac. Liver tissue was collected for biochemical and histological analysis. Primary rat hepatocytes were treated with diclofenac (400 µmol/L) with and without pretreatment with Opuntia extract. Apoptosis was measured by caspase-3 activity and necrosis by Sytox green staining. RNA was isolated, and real-time qPCR was performed to assess mRNA levels of stress and apoptosis-related genes MnSOD (SOD2), GADD45B and P53. ROS production was measured using the fluorescent MitoSOX assay. Results demonstrated that Opuntia spp -extracts protect against DF-induced liver toxicity via reducing oxidative stress and the inhibition of P53.

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