Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway

更新时间:2023-05-28

【摘要】We investigated the liver protective activity of dandelion polyphenols(DP) against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups(n = 9 per group): Control, APAP, APAP + DP(100 mg·kg–1), APAP + DP(200 mg·kg–1), and APAP + DP(400 mg·kg–1) groups. Mice were pretreated with DP(100, 200, and 400 mg·kg–1) by oral gavage for 7 d before being treated with 350 mg·kg–1 APAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance(superoxide dismutase,SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors(tumor necrosis factor-α, TNF-α; interleukin-1β,IL-1β). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

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