Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview

Abstract

The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for drug-induced liver damage. Endorsed medications represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and natural products in the treatment of various disorders led the investigators to look into their potential in countering drug-induced liver toxicity. Several natural products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less adverse reactions of the natural products provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication.

Keywords: antioxidant; hepatoprotection; hepatotoxicity; herbal medicine.

Figure 1

Factors affecting drug-induced hepatic toxicity. Various factors, such as, advancing age, gender, lifestyle factors, obesity, nutritional status, genetic background, dose, and duration of drugs may increase the risk of drug-mediated hepatotoxic reactions.

Figure 2

Overview of mechanism of drug and xenobiotic metabolism and effects of herbal antioxidants. Induction of nuclear receptors by drugs and xenobiotics lead to translocation in the nucleus where they increase the expression of cytochrome P450 enzymes. The activity of these enzymes generates reactive metabolites and free radicals which in turn bind to macromolecules, cause membrane lipid peroxidation, and increase cellular toxicity. Natural products increase the expression of phase II enzymes, the level of intracellular antioxidant (GSH), and antioxidant enzymes. The natural products may also inhibit the activities of cytochrome P450 enzymes in order to attain dynamic homeostasis and reduce cellular toxicity.