Quercetin in vesicular delivery systems: evaluation in combating arsenic-induced acute liver toxicity associated gene expression in rat model.
Arsenic, the environmental toxicant causes oxidative damage to liver and produces hepatic fibrosis. The theme of our study was to evaluate the therapeutic efficacy of liposomal and nanocapsulated herbal polyphenolic antioxidant quercetin (QC) in combating arsenic induced hepatic oxidative stress, fibrosis associated upregulation of its gene expression and plasma TGF beta (transforming growth factor beta) in rat model. A single dose of arsenic (sodium arsenite-NaAsO(2), 13 mg/kgb.wt) in oral route causes the generation of reactive oxygen species (ROS), arsenic accumulation in liver, hepatotoxicity and decrease in hepatic plasma membrane microviscosity and antioxidant enzyme levels in liver. Arsenic causes fibrosis associated elevation of its gene expression in liver, plasma TGF ss (from normal value 75.2+/-8.67 ng/ml to 196.2+/-12.07 ng/ml) and release of cytochrome c in cytoplasm. Among the two vesicular delivery systems formulated with QC, polylactide nanocapsules showed a promising result compared to liposomal delivery system in controlling arsenic induced alteration of those parameters. A single dose of 0.5 ml of nanocapsulated QC suspension (QC 2.71 mg/kg b.wt) when injected to rats 1h after arsenic administration orally protects liver from arsenic induced deterioration of antioxidant levels as well as oxidative stress associated gene expression of liver. Histopathological examination also confirmed the pathological improvement in liver. Nanocapsulated plant origin flavonoidal compound may be a potent formulation in combating arsenic induced upregulation of gene expression of liver fibrosis through a complete protection against oxidative attack in hepatic cells of rat liver.
Ghosh
Debasree
D
Biomembrane Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, India. dbsrghsh@yahoo.com
Ghosh
Swarupa
S
Sarkar
Sibani
S
Ghosh
Aparajita
A
Das
Nirmalendu
N
Das Saha
Krishna
K
Mandal
Ardhendu K
AK
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001151:Arsenic / Q000009:adverse effects*; D024042:Collagen Type I / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D053769:Nanocapsules / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood
D000975:Antioxidants; D024042:Collagen Type I; D008081:Liposomes; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D045304:Cytochromes c; D011794:Quercetin; D001151:Arsenic