PMID:
Life Sci. 2018 Nov 15 ;213:174-182. Epub 2018 Oct 13. PMID: 30326221
Abstract Title:
Formononetin and biochanin A protects against ritonavir induced hepatotoxicity via modulation of NfκB/pAkt signaling molecules.
Abstract:
AIMS: Ritonavir (RIT) is a human immune deficiency virus (HIV) protease inhibitor (PI) active against HIV-1 and HIV-2. Among various adverse effects of PIs, hepatotoxicity is a very common adverse reaction of RIT which is concentration dependent. Red clover isoflavones are found to possess anti-inflammatory, antioxidant and anti-apoptosis activity. Furthermore, recent studies have demonstrated that these isoflavones can be used to alleviate the side-effects of drugs. Hence, the present study was inquested to ascertain the effect of Formononetin (FMN) and Biochanin A (BCA) on RIT induced hepatotoxicity.MAIN METHODS: Five groups of animals were subjected to treatment as control, toxic control (RIT), third group (RIT + FMN), fourth group (RIT + BCA), the fifth group (RIT + FMN + BCA) and sixth group (FMN + BCA) for 14 days. The animals were evaluated for estimation of liver toxicity markers, inflammatory biomarkers, in-vivo biochemical antioxidant parameters. The liver tissues were furtherevaluated histopathologically and western blotting examination for localization of apoptotic gene expression that plays a pivotal role in hepatotoxicity.KEY FINDINGS: FMN and BCA ameliorated the increased levels of biochemical markers of liver, attenuated the RIT induced Bax, caspase-3, NFκB and eNOS activation and persuaded the Bcland pAkt level. Alteration in the levels of inflammatory markers was also observed in both hepatic tissue and serum.SIGNIFICANCE: FMN and BCA exerts hepatoprotective effect through modulating the oxidative stress, inflammation, apoptosis and reversing the tissue degeneration suggesting its therapeutic role in hepatotoxicity and other hepatocellular diseases.
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