Sinapic acid mitigates methotrexate‐induced hepatic injuries in rats through modulation of Nrf‐2/HO‐1 signaling. Issue 7 (15th March 2021)

• Record Type: Journal Article
• Authors: Ahmad, Ajaz; Alkharfy, Khalid M.; Bin Jardan, Yousef A.; Shahid, Mudassar; Ansari, Mushtaq Ahmad; Alqahtani, Saeed; Jan, Basit L.; Al‐Jenoobi, Fahad I.; Raish, Mohammad
• Is Part Of: Environmental toxicology. Volume 36:Issue 7(2021)
• Page Start: 1261
• Page End: 1268
• Publication Date: 2021-03-15
• Subjects: hepatic injury -- methotrexate -- Nrf2/HO‐1 and NF‐κB -- oxidative stress -- sinapic acid; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.23123
• Languages: English
• ISSNs: 1520-4081

Abstract

Abstract: 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.