The involvement of TGF-β1 /FAK/α-SMA pathway in the antifibrotic impact of rice bran oil on thioacetamide-induced liver fibrosis in rats

Abstract

The objective of the current study is to investigate the effect of rice bran oil (RBO) on hepatic fibrosis as a characteristic response to persistent liver injuries. Rats were randomly allocated into five groups: the negative control group, thioacetamide (TAA) group (thioacetamide 100 mg/kg thrice weekly for two successive weeks, ip), RBO 0.2 and 0.4 groups (RBO 0.2mL and 0.4 mL/rat/day, po) and standard group (silymarin 100 mg/kg/day, po) for two weeks after TAA injection. Blood and liver tissue samples were collected for biochemical, molecular, and histological analyses. Liver functions, oxidative stress, inflammation, liver fibrosis markers were assessed. The obtained results showed that RBO reduced TAA-induced liver fibrosis and suppressed the extracellular matrix formation. Compared to the positive control group, RBO dramatically reduced total bilirubin, AST, and ALT blood levels. Furthermore, RBO reduced MDA and increased GSH contents in the liver. Simultaneously RBO downregulated the NF-κβ signaling pathway, which in turn inhibited the expression of some inflammatory mediators, including Cox-2, IL-1β, and TNF-α. RBO attenuated liver fibrosis by suppressing the biological effects of TGF-β1, α-SMA, collagen I, hydroxyproline, CTGF, and focal adhesion kinase (FAK). RBO reduced liver fibrosis by inhibiting hepatic stellate cell activation and modulating the interplay among the TGF-β1 and FAK signal transduction. The greater dosage of 0.4 mL/kg has a more substantial impact. Hence, this investigation presents RBO as a promising antifibrotic agent in the TAA model through inhibition of TGF-β1 /FAK/α-SMA.

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis

“…For this reason, we decided to explore the possible protective role of empagliflozin (EMPA) in curbing the progression of liver fibrosis in thioacetamide (TAA)-intoxicated rats via targeting AMP-activated protein kinase (AMPK)/Sirtuin-1 (SIRT-1) activity and via inhibiting Hypoxia-inducible factor 1-alpha (HIF-1α). TAA is a well-known hepatotoxin that causes fibrosis in rats nearly irreversible and identical to human fibrosis, making it a good model for testing prospective antifibrotic medicines [ 4 , 24 ]. In the current study, the administration of TAA thrice weekly to rats induced an enormous elevation in serum ALT, AST, GGT, and ammonia, accompanied by a sharp decline in serum albumin.…”

“…It also impedes mitochondrial function, which ultimately causes cellular destruction and the death of hepatocytes. TAA is a well-known liver toxin that causes hardly reversible fibrosis in rats that is similar to that in humans, making it an excellent model for testing prospective antifibrotic medications [ 4 , 5 ].…”

Thymol ameliorated neurotoxicity and cognitive deterioration in a thioacetamide-induced hepatic encephalopathy rat model; involvement of the BDNF/CREB signaling pathway

“…9,21 Rats in the HE, reference and treated groups were intraperitoneally injected with TAA (100 mg kg −1 , three times per week, for two weeks). 22 The treated groups were orally administered Vit E, THY-30 or THY-60, daily for 1 month. The initial and final body weights of all the animals were recorded.…”

Antidiabetic Effect of Hexane Extract of Costus Speciosus and Metformin in Rats

“…The chemicals were tentatively identified by comparing the mass spectra and retention times of the compounds to the NIST and WILLY library data from the GC/MS instrument [12].…”