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

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...

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Published in:Environmental toxicology 2021-07, Vol.36 (7), p.1261-1268
Main 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
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Apoptosis
Carboxymethyl cellulose
Carboxymethylcellulose
Cellulose
Cytokines
Damage prevention
Defence mechanisms
hepatic injury
Histopathology
Inflammation
Intravenous administration
Liver
Methotrexate
Nrf2/HO‐1 and NF‐κB
Oxidative stress
Pretreatment
Signaling
Sinapic acid
Sodium chloride
Tumor necrosis factor
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Summary: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.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.23123