Screening Methods for the Evaluation of Hepatoprotective Agents

Abstract

Liver being the major site of metabolism of xenobiotics, it is predisposed to the harmful effects of the toxic metabolites generated during biotransformation. Drugs designed to prevent this damage are referred to as hepatoprotective agents. To determine the safety and efficacy of the potential hepatoprotective agents, a plethora of screening methods are available both in vitro and in vivo. Some of the commonly used hepatoprotective agents are N-acetyl cysteine, d-penicillamine, s-adenosyl methionine (SAM), melatonin, L-carnitine etc. Plant derivatives like Silybum marianum, Curcuma longa, Camellia sinensis and Glycyrrhiza glabra are also used frequently to name a few.The in vitro screening methods utilize fresh hepatocytes, primary hepatocyte culture and immortalized cell lines for screening hepatoprotective agents. Cell viability test is a in vitro method while precision cut liver slices (PCLS) and isolated perfused liver are ex vivo screening methods.The in vivo screening methods frequently use the Sprague dawley rat for pretreatment with hepatotoxins. The hepatotoxins used are acryl amide, alcohol, adriamycin, cadmium chloride, carbon tetrachloride, erythromycin stearate, galactosamine, paracetamol, tamoxifen, t-BHP and olanzapine.Other models used are chloroform model, hypoxia model, diclofenac model, isoniazid and rifampicin model, concavalin A & lipopolysaccharide model. The hepatoprotective effect is assessed by the morphology, biochemistry and histopathological parameters.