The protective role of melatonin in rat hippocampal injuries induced by intermittent hypoxia

• Published in: The FASEB journal 2007, Vol.21 (6), p.A824-A824
• Main Authors: Hung, Ming Wai, Tipoe, George L., Poon, Angela MS, Shiu, Stephen YW, Fung, M L
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A824-a

We evaluated the hypothesis that melatonin reduces hippocampal injuries with an increased expression of antioxidant enzymes during intermittent hypoxia (IH). Adult Sprague‐Dawley rats received daily injection of melatonin or vehicle for 7 (D7), 14 (D14) and 28 days (D28) in IH chambers for 8 hr/day diurnally. Serum and hippocampus were harvested for the measurement of malondialdehyde (MDA). The mRNA levels of inflammatory mediators including TNFα, iNOS, COX‐2 and antioxidant enzymes including glutathione peroxidase, catalase, copper/zinc superoxide dismutase in the hippocampus were studied by RT‐PCR. Apoptosis was studied histologically in hippocampal sections. Our results showed significant increases in the cell death, levels of serum and hippocampal MDA and mRNA levels of inflammatory mediators in vehicle groups compared with the normoxic control, but mRNA levels of the antioxidant enzymes were decreased in those groups. The serum MDA level of melatonin groups was comparable to that of the normoxic control. Melatonin groups showed reduction in hippocampal MDA level and apoptosis compared with vehicle groups. Melatonin groups on D7 and D14 showed decreased expression of those mediators with elevated expressions of antioxidant enzymes compared with vehicle groups. However, melatonin had no effect on the expressions in inflammatory mediators or antioxidant enzymes on D28. These results suggest that melatonin reduces oxidative stress and delays the pathogenesis of IH‐induced hippocampal injuries with its anti‐oxidant and anti‐inflammatory properties via transcriptional regulation of antioxidant enzymes. The transcriptional regulation may explain the protective effect against apoptosis in the early days of IH exposure.