Renal effects of 7,8-Dihydroxyflavone in cafeteria diet-induced obesity

Abstract

Objective: In this study, the possible protective effect of 7,8-Dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor (BDNF) mimetic and anti-oxidant flavonoid, in renal damage caused by cafeteria diet-induced obesity was investigated. Method: In the study, 4-5 week old C57BL/6 male mice were used and the subjects were divided into 4 groups as Control, CD (cafeteria diet), CD+Vehicle and CD+7,8-DHF (n=9-11). Control group subjects were fed with chow diet for 16 weeks and other groups were fed with cafeteria diet. In the last 28 days of the feeding period, 7,8-DHF treatment (5 mg/kg/day, intraperitoneal) was administered in the CD+7,8-DHF group, and DMSO (17%) as a 7,8-DHF carrier was administered in the CD+Vehicle group. At the end of 16 weeks, the subjects were sacrificed and malondialdehyde (MDA), reduced glutathione (GSH), nitrite + nitrate (NOx) and collagen levels, and superoxide dismutase (SOD) and catalase (CAT) enzyme activities were measured in kidney tissues. Results: At the end of 16 weeks, body weights of all subjects increased compared to baseline. Weight gain was higher in CD (p<0.001) and CD+Vehicle groups (p<0.001) compared to control. The weight gain in the CD+7,8-DHF group was not different from the control. Compared to the CD group, the weight gains in the CD+Vehicle and CD+7,8-DHF groups were lower. Compared to the control group CD group had higher renal MDA level (p<0.0001), lower GSH level (p<0.0001), less SOD (p<0.0001) and CAT (p<0.0001) activity, lower NOx (p<0.0001) and collagen (p<0.0001) levels. Vehicle administration did not affect these parameters as results were similar to CD group. However, significant changes were noted with 7,8-DHF treatment. Compared with the CD+Vehicle group, the CD+7,8-DHF group had lower MDA levels (p<0.001), higher GSH levels (p<0.001), lower NOx levels (p<0.001), higher SOD (p<0.001) and CAT (p<0.001) activities. 7,8-DHF treatment brought these parameters closer to the control values, but did not fully return to control, except for CAT activity. Renal collagen deposition was not affected by 7,8-DHF treatment. Conclusion: Oxidative stress plays an important role in obesity-induced renal damage. 7,8-DHF may be important in the suppression of renal damage in cafeteria diet-induced obesity, at least by inhibiting oxidative stress and excessive nitric oxide production. The increasing prevalence of eating habits and obesity together with the cafeteria diet in the society, makes these results clinically important. These effects of 7,8-DHF need to be investigated in more details.