Modulation of Nitric Oxide Synthase and Superoxide Dismutase Gene Expression by Altered Thyroid Levels in Adult Rat Brain

The effects of altered thyroid hormones level (through induction of Hypothyroidism or Hyperthyroidism) on oxidative stress and antioxidant biomarkers as well as on gene expression of neuronal nitric oxide synthase and superoxide dismutase of adult male rat brain were studied. Hypothyroidism was induced by daily intraperitoneal (i.p.) injection of propylthiouracil (PTU, 10 mg/kg body weight) for 4 weeks. Hyperthyroidism was elicited by daily i.p. injection of L-thyroxine (L-T4, 300 μg/kg body weight) for 3 weeks. In hypoor hyperthyroid rats, significant increases in malondialdehyde and nitric oxide concentrations associated with significant decreases in reduced glutathione content, superoxide dismutase and catalase activities were recorded compared to the controls. Activity of glutathione peroxidase was increased in hypoand hyperthyroid rats compared to control rats. Augmentation in the gene expression of neuronal nitric oxide synthase and decline in the gene expression of superoxide dismutase was observed in both hypoand hyperthyroid rat brain. DNA damage of brain was higher in the two thyroid hormone states compared to the control groups. The random amplified polymorphic DNApolymerase chain reaction (RAPD-PCR) analysis indicated the presence of 48 % new bands (polymorphic) in hypothyroid (PTU) and hyperthyroid (L-T4) treated brain samples and the absence of such bands in the control groups. Marked histopathological alterations were also observed in brain sections of either hypoor hyperthyroid rats. These results provide evidence that the changes in the oxidative stress and antioxidant status in altered thyroid hormone levels are exerted through modulation of neuronal nitric oxide synthase and superoxide dismutase gene expression in adult rat brain.