1. Formononetin and biochanin A protects against ritonavir induced hepatotoxicity via modulation of NfκB/pAkt signaling molecules.
- Author
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Alauddin, Chaturvedi S, Malik MY, Azmi L, Shukla I, Naseem Z, Rao C, and Agarwal NK
- Subjects
- Animals, Antioxidants pharmacology, Apoptosis drug effects, Chemical and Drug Induced Liver Injury metabolism, Genistein metabolism, Isoflavones metabolism, Liver drug effects, Liver Diseases metabolism, Male, NF-kappa B metabolism, Oxidative Stress drug effects, Protective Agents pharmacology, Proto-Oncogene Proteins c-akt metabolism, Rats, Rats, Sprague-Dawley, Ritonavir adverse effects, Genistein pharmacology, Isoflavones pharmacology, Liver metabolism
- 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 further evaluated 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 Bcl
2 and 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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