Sinapic acid mitigates methotrexate‐induced hepatic injuries in rats through modulation of Nrf‐2/HO‐1 signaling

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.

Sinapic Acid Attenuated Cardiac Remodeling After Myocardial Infarction by Promoting Macrophage M2 Polarization Through the PPARγ Pathway

“…Sinapic acid (SA) is a hydroxycinnamic acid derivative that has been proven to have protective effects on different disease models, such as liver injury ( 8 ), hepatitis ( 9 ), nephrotoxicity ( 10 , 11 ), gastric ulcer ( 12 ), lung fibrosis ( 13 ) and epilepsy ( 14 ). An increasing number of studies have also found that SA exerts a cardioprotective effect.…”

Amelioration of Hepatic Injury by Camel’s Biological Fluids Through the Modulation of Nf-Κb and Nrf2/Ho-1 Singling Pathway

“…D-Gal administration causes the release of reactive oxygen species (ROS), which damage liver tissues [36,59,69]. It is clearly demonstrated here the potential of effect of D-Gal to induce oxidative stress in the liver as evidenced by elevated levels of oxidative stress by MDA and MPO and a significant decline in the antioxidant defences by SOD, CAT and GSH [4,12,21] These results are concurrent with the results of Zeweil et al, [67] and Balkan et al, [13]. Conversely, the pre-treatment with camel's milk and urine maintained the plasma levels of MDA, SOD, CAT, MPO and GSH within normal ranges, which could be attributed to the presence of bioactive constituents in camel's milk and urine with powerful radical scavenging activity.…”

Sinapis Semen: A review on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics

“…On the one hand, sinapic acid ( 2 ) in SS inhibits bromodomain containing 4 (BRD4) expression and suppresses oxidative stress, cell scorching and hepatocyte injury ( Chu et al, 2021 ). On the other hand, SS can prevent methotrexate (MTX)-induced liver injury by inhibiting apoptosis and stimulating Nrf2/HO-1-intermediate antioxidant enzymes through NF-κB inhibition ( Ahmad et al, 2021 ). Sinapine ( 1 ) modulate the composition of intestinal flora, induce a decrease in the ratio of thick-walled phylum and mimic phylum, and increase the abundance of probiotic bacteria, thereby inhibiting hepatic steatosis ( Li et al, 2019 ).…”