EFFECTS OF ALL-TRANS RETINOIC ACID ON REDUCING HYPEROXIA-INDUCED OXIDATIVE STRESS IN MICE BRAIN.

Abstract

ABSTRACTObjective: Brain is a very sensitive organ to oxidative stress due to its large amount of polyunsaturated fatty acid content and low antioxidant activity. In this study, effect of exogenous all-trans-retinoic acid (RA) on brain antioxidant activity was investigated in mice under hyperoxia-induced oxidative stress.Material and Method: Adult C57BL/6J mice were divided into 4 groups. Two groups were given daily either peanut oil/dimethylesulfoxide (PoDMSO) mixture or 50 mg/kg RA dissolved in PoDMSO (RA-PoDMSO). The remaining two groups were treated with PoDMSO or RAPoDMSO as described above, following hyperoxia (100% oxygen) for 72 h. The treatments were given daily 50 µl intraperitoneal injections for 12 days, with a 2 day interruption on days 6 and 7. Lipid peroxidation (LPO) and glutathione (GSH) levels as well as activities of several antioxidant enzymes were assayed in brain tissue to evaluate oxidative stress, biochemically.Results: Elevated LPO levels, increased catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase activities, and decreased GSH levels were observed in hyperoxic mice. RA administration to hyperoxic mice improved these biochemical alterations in favour of reduced oxidative stress.Conclusion: Exogenous RA, a small lipophilic molecule, is effective in reducing oxidative stress in the brain which can receive only small lipophilic molecules due to the presence of the blood-brain barrier. Also, RA exhibits an antioxidant effect by inhibiting the GSH depletion and increased LPO levels in brain of hyperoxic mice, directly.