Mechanism of protection of rat hepatocytes from acetaminophen-induced cellular damage by ethanol extract of Aerva lanata

The aim of this study is to evaluate the protective effect of ethanol extract of Aerva lanata (EEAL) in preventing acetaminophen induced liver toxicity. EEAL was prepared and its hepatoprotective effect was studied in both isolated primary hepatocytes in vitro and in Sprague Dawley rats in vivo. For in vivo studies, the animals were grouped as Group I - Control; Group II - ACN (2 g/kg b.w.); Group III - EEAL (50 mg/kg b.w.) + ACN (2 g/kg b.w.), Group IV - EEAL (100 mg/kg b.w.) + ACN (2 g/kg b.w.). Extracellular activities of the enzymes liver aminotransferease (GOT, GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in isolated hepatocytes and rat plasma were studied colorimetrically. Expression of GST, Nrf2, COX 1 & COX2 genes in rat liver were evaluated by RT-PCR. The results showed that ACN induced down-regulation of Nrf2 and upregulation of GST gene expression, which were modulated by EEAL treatment. GOT, GPT, ALP and LDH levels were found to be lowered in both hepatocyte culture media and plasma following EEAL treatment. In addition, the medium GOT and GPT levels were diminished following EEAL treatment only. Moreover, only ALP and LDH in serum appeared to be at normal level following EEAL treatment, whereas GOT and GPT showed levels lower than control. ACN treatment increased the expression of pro-inflammatory COX 1 and COX 2 genes and the levels of these genes were reduced by EEAL treatment. EEAL pre-treated rats exposed to ACN were found to retain normal hepatic structure compared to ACN alone treated rats. From these results it can be concluded that ethanol extract of A. lanata possesses both anti-inflammatory and hepatoprotective activity.

Keywords: Aerva lanata; Nrf2; acetaminophen; cyclooxygenases; hepatotoxicity.