Paper Information

Title: 

PROTECTIVE EFFECTS OF FUNGAL (1-3)-β-D-GLUCAN AGAINST OXIDATIVE STRESS CYTOTOXICITY INDUCED BY DEPLETED URANIUM IN ISOLATED RAT HEPATOCYTES

Type: POSTER
Author(s): POURAHMAD J.*,TANBAKOUSAZAN F.,SHAKI F.
 
 *FACULTY OF PHARMACY, SHAHEED BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Polymeric carbohydrates have been reported to modulate inflammatory responses in vitro and in vivo. Previous reports suggest that certain carbohydrate polymers, such as (1-3)-b-d-glucan, may possess free radical scavenging activity. If glucans are free radical scavengers then it might explain, in part, the ability of these ligands to modulate inflammatory responses. The present study examined the free radical scavenging activity of a carbohydrate polymer, (1-3)-b-d-glucan against oxidative stress induced by depleted uranium in isolated rat hepatocytes. Addition of U(VI) (uranyl acetate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture before hepatocyte lysis occurred. Our results showed that tiny oncentration of (1-3)- b-d-glucan (138 nM) very successfully protected the hepatocytes against cell lysis and all oxidative stress endpoints caused by depleted uranium including glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture. We have already shown that U(VI) reductive activation to U(IV) required for its toxicity and carcinogenicity is mediated via NADPH - P450 reductase and reduced CYP 2E1. Our results also showed that depleted uranium cytotoxicity, glutathione depletion, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture were prevented by ROS scavengers, antioxidants, and inhibitors of NADPH - P450 reductase and CYP 2E1. In conclusion, our results confirmed the previous reports regarding the antioxidant and radical scavenging activity of (1-3)-b-d-glucan and also suggested some P450 inhibitory activity for this carbohydrate polymer.

 
Keyword(s): (1-3)-β-D-GLUCAN, DEPLETED URANIUM, HEPATOPROTECTION, OXIDATIVE STRESS
 
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