Ameliorating Effect of Idebenone and/or Melatonin against Oxidative Stress and Energy

In the current study, the protective effect of idebenone (200mg/kg, i.p.), melatonin (10 mg/kg, i.p.) and their combination on oxidative stress markers (lipid peroxidation, reduced glutathione (GSH), Lascorbic acid, superoxide dismutase (SOD), catalase (CAT); total nitrate/nitrite and uric acid), as well as brain ATP content was estimated in sodium nitrite-induced hypoxia in rats' brain. Brain membrane integrity was assessed by measuring serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and sialic acid. The drugs were administered 24 and 1 h prior sodium nitrite administration. All biochemical parameters were estimated one hour after sodium nitrite injection. Injection of sodium nitrite (75 mg/kg, s.c.) produced a significant disturbance in membrane permeability and oxidative status of rats brain in addition to a significant depletion in ATP content. Neuronal damage was confirmed by histopathological examination of the brain. Compared to hypoxic rats, pretreatment with either idebenone or melatonin exhibited significantly reduced levels of serum LDH, CK, sialic acid, nitrate/nitrite and uric acid as well as brain lipid peroxides. Although both drugs significantly preserved the activities of SOD and CAT in brain tissues, only idebenone showed a significant elevation of GSH and ascorbic acid compared to hypoxic group. Both drugs showed a significant elevation of brain ATP contents compared to hypoxic rats. Combination of both idebenone and melatonin exerts a significant amelioration of oxidative stress markers with significant improvement in ATP content compared to each drug alone. The marked changes in cerebellar Purkinji cells induced by sodium nitrite were completely abolished by pretreatment with drug combination. It could be concluded that combination of both idebenone and melatonin provides potential protection against sodium nitrite-induced hypoxia via improving antioxidant defense system and preserving brain energy content