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Hepatoprotective activity of Silymarin against Acetaminophen invo | 3972
Drug Designing: Open Access

Drug Designing: Open Access
Open Access

ISSN: 2169-0138

+44 1223 790975

Hepatoprotective activity of Silymarin against Acetaminophen involves an enhancement of the Glutathione-dependent detoxification capacity


International Conference and Expo on Drug Discovery & Designing

August 11-13, 2015 Frankfurt, Germany

Young Chul Kim, Do Young Kwon, Chul Won Ahn and Doo Sung Jun

Scientific Tracks Abstracts: Drug Des

Abstract :

We previously showed that silymarin was capable of increasing hepatic glutathione (GSH) levels via a modification of the
transsulfuration reactions in liver. To investigate its pharmacological significance we determined the effects of silymarin
pretreatment on the acetaminophen (APAP)-induced hepatotoxicity. Male mice were treated with silymarin (200 mg/kg, po) every
12 h for a total of 3 doses prior to APAP challenge (500 mg/kg, ip). Silymarin pretreatment attenuated the liver injury significantly
as determined by inhibition of the increase in plasma enzyme activities, lipid peroxidation and formation of nitrotyrosine protein
adducts in liver. Concentrations of APAP, APAP-glucuronide or APAP-sulfate were not changed, but thiol-conjugates of APAP, such
as APAP-GSH, APAP-cysteine and APAP-N-acetylcysteine, were elevated in plasma. However, silymarin treatment did not induce
protein expression of Cyp2e1, Cyp1a2, and Cyp3a11, the major isoforms involved in metabolic activation of APAP. Comparable
results were obtained with hepatic microsomal activities measured using p-nitrophenol, ethoxyresorufin and erythromycin,
indicating that the increased generation of APAP-thiol conjugates should be attributed to an augmentation of the GSH conjugation
capacity. It is suggested that silymarin may prevent the APAP-induced hepatotoxicity by increasing GSH availability which enhances
the detoxifying capacity of liver cell against the toxic electrophile generated from this analgesic-antipyretic

Biography :

Young Chul Kim is a Professor of Toxicology at Seoul National University, College of Pharmacy since 1986. He received his MS and from Purdue University, and completed
Postdoctoral studies at the National Institute of Environmental Health Sciences (NIEHS), NIH, USA. He has published more than 100 papers in reputed journals. He is
a recipient of several prestigious international and national awards including the Thieme Most Innovative Original Paper Award at GA and the Korean Teachers’ Award.

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