Swati Chaturvedi1, Mohd Yaseen Malik2, Lubna Azmi3, Ila Shukla3, Zaiba Naseem4, ChandanaVenkateswara Rao3, Naresh Kumar Agarwal5. 1. Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India. 2. National Institute of Pharmaceutical Education & Research, Opp. Bhawani Paper Mill, Raebareli, U.P., India. 3. Pharmacognosy and Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India. 4. Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India. 5. Department of Zoology, HNB Garhwal Central University, Campus Badshahithaul TehriGarhwal, Uttarakhand, India.
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 Bcl2 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.
AIMS: Ritonavir (RIT) is a humanimmune 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 cloverisoflavones 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 Bcl2 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.
Authors: Luis E Soria-Jasso; Raquel Cariño-Cortés; Víctor Manuel Muñoz-Pérez; Elizabeth Pérez-Hernández; Nury Pérez-Hernández; Eduardo Fernández-Martínez Journal: Int J Mol Sci Date: 2019-09-22 Impact factor: 5.923