The effect of 7,8-dihydroxyflavone on age related oxidative stress and nitric oxide depletion

Abstract

Purpose: It has been reported that 7,8-dihydroxyflavone (7,8-DHF), known as a brain-derived neurotrophic factor (BDNF) receptor agonist, affects nitric oxide (NO) production as well as its antioxidant properties. Although favorable effects of 7,8-DHF have been reported in the central nervous system in aged rodents, its effects on non-neural tissues are not fully understood yet. In the literature, it has been stated that liver, kidney and heart tissues show age-related oxidative stress and NO dysregulation. In this study, the effects of 7,8-DHF on oxidative stress and NO production in liver, kidney and heart tissues in aged mice were investigated.Materials and methods: Male C57BL/6 mice were divided into 3 groups as young (5 months old, n=10), elderly (18 months old, n=10) and DHF-elderly (18 months old, n=7). The mice in DHF-elderly group were treated with 7,8-DHF (5 mg/kg-1.day-1, intraperitoneally) for 3 weeks. The malondialdehyde (MDA), reduced glutathione (GSH) and nitrite/nitrate (NOx) levels were measured in the liver, heart and kidney tissues of mice.Results: Hepatic MDA increase (p<0.001) and GSH decrease (p<0.01) observed in the elderly group were significantly reversed with 7,8-DHF treatment. Unchanged hepatic NOx level in the elderly group, increased with 7,8-DHF treatment (p<0.001). 7,8-DHF treatment did not affect the age-related increase in renal MDA, but attenuated the renal GSH (p<0.05) and NOx (p<0.001) decrements. 7,8-DHF treatment did not affect cardiac oxidative stress, but attenuated age-related NOx reduction (p<0.001).Conclusion: 7,8-DHF was effective in preventing age-related oxidative stress in hepatic and renal tissue, and age-related NO decrement in liver, heart and kidney. 7,8-DHF might be a promising compound in preventing age related functional loss in non-neural tissues. Further studies are needed to reveal all effects of this compound.