The present research has been investigated to study the protective outcomes of sinapic acid (SA) against methotrexate (MTX) encouraged liver damage in rats by modulating the Nrf2/HO-1 and NF-κB signaling pathways. The animals were arbitrarily allocated into four groups: group I rats administered a 0.5% carboxymethyl cellulose (CMC) vehicle orally for 15 consecutive days with a single intravenous standard saline injection (0.9% NaCl) on day seven. Groups II, III, and IV were injected intraperitoneally with 20 mg MTX/kg on 7th day. Animals in group III and IV were treated orally for 14 days with 20 mg of SA/kg dissolved daily in 0.5% CMC respectively. In all experimental groups, liver function, biochemical, histopathological and molecular changes were evaluated. MTX-induced changes in liver function indices like ALT, AST, and ALP are substantially restored with SA pretreatment. Moreover, antioxidant defense mechanisms (GSH, SOD, and CAT) and oxidative/nitrostative stress (MDA and NO) and inflammatory cytokine (TNF-α, IL-β and MPO) were also substantially restored. Furthermore, the conclusions indicate that SA prevents the hepatic damage caused by MTX through apoptosis inhibition and stimulation of Nrf2/HO-1-medial antioxidant enzymes by NF-κB inhibition. Histological findings have shown that SA therapy has greatly protected liver damage caused by MTX.
Keywords: Nrf2/HO-1 and NF-κB; hepatic injury; methotrexate; oxidative stress; sinapic acid.
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