Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation

Abstract

Bromobenzene is a well-known environmental toxin which causes liver and kidney damage through CYP450-mediated bio-activation to generate reactive metabolites and, consequently, oxidative stress. The present study aimed to evaluate the possible protective role of withaferin A against bromobenzene-induced liver and kidney damage in mice. Withaferin A (10 mg/kg) was administered orally to the mice for 8 days before intragastric intubation of bromobenzene (10 mmol/kg). As results of this experiment, the levels of liver and kidney functional markers, lipid peroxidation, and cytokines (TNF-α and IL-1β) presented an increase and there was a decrease in anti-oxidant activity in the bromobenzene-treated group of mice. Pre-treatment with withaferin A not only significantly decreased the levels of liver and kidney functional markers and cytokines but also reduced oxidative stress, as evidenced by improved anti-oxidant status. In addition, the mitochondrial dysfunction shown through the decrease in the activities of mitochondrial enzymes and imbalance in the Bax/Bcl-2 expression in the livers and kidneys of bromobenzene-treated mice was effectively prevented by pre-administration of withaferin A. These results validated our conviction that bromobenzene caused liver and kidney damage via mitochondrial pathway and withaferin A provided significant protection against it. Thus, withaferin A may have possible usage in clinical liver and kidney diseases in which oxidative stress and mitochondrial dysfunction may be existent.

A biochemical approach to the anti-inflammatory, antioxidant and antiapoptotic potential of beta-carotene as a protective agent against bromobenzene-induced hepatotoxicity in female Wistar albino rats

“…The GSH pool is depleted due to the conjugation of epoxides formed by biotransformation of BB, when it is delivered in high doses (Kluwe et al, 1984). Hepatotoxicity induced by BB is characterized by a depletion in glutathione in both mitochondria and cytosol, succeeded by a diminution in mitochondrial respiration at complexes I and II during the start of hepatotoxicity (Vedi and Sabina, 2016). Pre-treatment with beta-carotene significantly increased the reduced glutathione levels brought about by the action of BB in our study.…”

Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells

“…Among these withanolides, withaferin A (WFA) is the most abundant and therapeutically effective withanolides with anti-cancer activities (6)(7)(8). WFA protects against acetaminophen-induced hepatic toxicity (9) and bromobenzene (an environmental toxin)-induced liver and kidney damage (10). Some clinical trials Downloaded from https://academic.oup.com/carcin/article-abstract/40/9/1110/5303994 by Semmelweis University user on 28 November 2019 have investigated the efficacy of W.somnifera extracts (Drug: Sensoril) for bipolar disorder, schizophrenia and generalized anxiety disorder (ClinicalTrials.gov Identifier: NCT00761761, NCT01311180, NCT01793935) and Schlicht and group reported that W.somnifera extracts provided significant benefits in patients with schizophrenia (11).…”

The pathophysiological role of mitochondrial oxidative stress in lung diseases

“…Mitochondrial dysfunction plays a crucial role in bioenergetics metabolism and non-energetics pathogenesis in many lung diseases [ 6 , 7 ]. The mitochondrial genome acts as a sentinel factor governing the cytotoxic response of lung cells to oxidant stress [ 8 , 9 ]. In this review, we highlight how ROS-induced mitochondrial dysfunction and damaged mitochondrial DNA (mtDNA) fragments are involved in the pathobiology of various degenerative lung diseases, pulmonary fibrosis, and lung tumorigenesis.…”