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Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model

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Title Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model
 
Creator SINGH, M
SASI, P
GUPTA, VH
RAI, G
AMARAPURKAR, DN
WANGIKAR, PP
 
Subject anti-TB drugs
Apoptosis
Cell cycle
Mitochondrial membrane potential
Herbal drugs
Adjuvant therapy
HepG2 cells
In vitro liver model
Flow cytometry
Cell viability
MTT assay
Cell cytotoxicity
Mitotracker (R) Red
Confocal microscopy
Sub-G1 peak
Drug metabolizing enzyme
Animal models
Human clinical trials
contrast microscopy
Adverse drug reactions
Propidium Iodide
Hypodiploid population
Tuberculosis
INDUCED HEPATIC-INJURY
PERMEABILITY TRANSITION
OXIDATIVE STRESS
CELL-CYCLE
RAT-LIVER
RIFAMPICIN
PYRAZINAMIDE
TOXICITY
MICE
IMMUNOSUPPRESSION
 
Description Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker (R) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs.
 
Publisher SAGE PUBLICATIONS LTD
 
Date 2014-10-15T08:06:56Z
2014-10-15T08:06:56Z
2012
 
Type Article
 
Identifier HUMAN & EXPERIMENTAL TOXICOLOGY, 31(8)788-797
http://dx.doi.org/10.1177/0960327111433901
http://dspace.library.iitb.ac.in/jspui/handle/100/14641
 
Language en