Protective effects of fungal β-(1→3)-D-glucan against oxidative stress cytotoxicity induced by depleted uranium in isolated rat hepatocytes.
Previous reports suggested that certain carbohydrate polymers, such as β-(1→3)-D-glucan, may possess free radical scavenging activity. The present study examined the free radical scavenging activity of a carbohydrate polymer, β-(1→3)-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 reactive oxygen species (ROS) formation, rapid glutathione depletion, mitochondrial membrane potential collapse and lysosomal membrane rupture before hepatocyte lysis occurred. Our results showed that quite similar to silymarin, which is a known antioxidant and radical scavenger, tiny concentration of β-glucan (138 nM) very successfully protected the hepatocytes against cell lysis and all oxidative stress cytotoxicity endpoints caused by depleted uranium including ROS formation, glutathione depletion, decreased mitochondrial membrane potential, lysosomal membrane rupture and caspase 3 activity increase. In conclusion, our results confirmed the antioxidant and radical scavenging activity of β-(1→3)-D-glucan and suggested this compound and silymarin as possible drug candidates for prophylaxis and treatment against depleted uranium toxic effects.
Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. j.pourahmadjaktaji@utoronto.ca
Jalal
J
Pourahmad
Fatemeh
F
Shaki
Farahnaz
F
Tanbakosazan
Ruhollah
R
Ghalandari
Hossein Ali
HA
Ettehadi
Ezzat
E
Dahaghin
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D014501:Uranium / Q000633:toxicity*; D047071:beta-Glucans / Q000494:pharmacology*
D000975:Antioxidants; D047071:beta-Glucans; D014501:Uranium