Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver.

AIM: To evaluate the in vivo effect of glutamine on cobalt-generated oxidative stress and (HO-1) induction in rat liver. METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 micromol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gln) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

Heme oxygenase-1 induction and dependent increase in ferritin. A protective antioxidant stratagem in hemin-treated rat brain.

The in vivo effect of hemin on both brain oxidative stress and heme oxygenase-1 (HO-1) induction was studied. A marked increase in lipid peroxidation was observed 1 h after hemin administration and antioxidant enzymes significantly decreased 3 h after hemin injection. HO-1 activity appeared 6 h after treatment, peaking 9 h after hemin administration. Such induction was preceded by a decrease in GSH pool and an increase in hydrogen peroxide concentration. Iron ferritin levels and ferritin content began to increase 6 h after HO-1 induction, and these increases remained high for at least 24 h after hemin injection. Administration of bilirubin entirely prevented HO-1 induction as well as the generation of oxidative stress parameters. These results indicate that the induction of heme oxygenase by hemin may be a general response to oxidant stress, by increasing bilirubin and ferritin levels and could therefore provide a major cellular defense mechanism against oxidative damage.