Abstract:
AIMS:Inducible nitric oxide synthase (iNOS) pathway has been in the limelight since its discovery as a key mediator in the process of liver fibrogenesis. Therefore, the objective of the current study was to elucidate the in vivo molecular mechanism underlying the hepatic preventive relevance of eugenol (EUG) and telmisartan (TEL) through iNOS pathway modulation against carbon tetrachloride (CCl4)-induced hepatic injury. METHODS:Sixty healthy male albino rats were used in this study. Serum aminotransferases activities and NO levels were assessed. Hepatic malondialdehyde (MDA), total nitrite/nitrate content and reduced glutathione (GSH) concentration were estimated. Liver NF-kB, TNF-α, IL-6 and iNOS proteins expressions were investigated by western blot assay. Histopathological examination was done. KEY FINDINGS:CCl4 resulted in damage to centrilobular regions of the liver, elevation of serum aminotransferases, rise in oxidative parameters level, and up-regulation of NF-kB, TNF-α, IL-6 as well as iNOS proteins expressions. Treatment of fibrotic rats with either EUG or TEL significantly alleviated CCl4-induced biochemical, inflammatory and histopathological changes. Moreover, the combined administration of EUG with TEL has an ameliorative effect which is greater than either of them alone. SIGNIFICANCE:In conclusion, the combination therapy between EUG and TEL is more effective than either drug alone which is attributed to suppression of NO production and iNOS protein expression. The results support that use of EUG and TEL exerts beneficial effects in the attenuation of CCl4-induced liver fibrosis in rats.
journal_name
Life Scijournal_title
Life sciencesauthors
Fathy M,Khalifa EMMA,Fawzy MAdoi
10.1016/j.lfs.2018.11.031subject
Has Abstractpub_date
2019-01-01 00:00:00pages
207-214eissn
0024-3205issn
1879-0631pii
S0024-3205(18)30744-6journal_volume
216pub_type
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