3‐Keto‐1,5‐bisphosphonates Alleviate Serum‐Oxidative Stress in the High‐fat Diet Induced Obesity in Rats

Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD ‐induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum‐oxidative stress markers. We also studied the effect of a chronic administration of 3‐keto‐1,5‐bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum‐oxidative stress status vocalized by an increase in ROS ( H ₂ O ₂ ), MDA and PC levels, with a decrease in antioxidant enzyme activity ( CAT , GP x , SOD ). Importantly, 3‐keto‐1,5‐bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3‐keto‐1,5‐bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications.