Reduction of oxidative stress induced vanadium toxicity by complexing with a flavonoid, quercetin: A pragmatic therapeutic approach for diabetes

Vanadium compounds are known to lower blood glucose level in diabetes but are associated with toxicity. In vitro cytotoxicity of VOSO4 and bis(quercetinato) oxovanadium(IV) (BQOV) was examined in CHO cells. Both the agents showed time and dose dependent increase in ROS generation however it was relatively less in BQOV. Moreover, VOSO4 also caused higher necrosis. Hypoglycemic potential of VOSO4 and BQOV was tested in streptozotocin-induced diabetic Balb/c mice. A marked difference was observed in the hypoglycemic action of VOSO4 and BQOV treated mice that lasted only for about 6 h in VOSO4 as against 24 h in BQOV. Comparison of acute toxicity of the compounds in normal Balb/c mice revealed negligible nephrotoxicity of BQOV. Kidney analyses of VOSO4 treated animals' revealed high ROS generation and tubular necrosis. Similarly serum levels of urea and creatinine were elevated in these animals indicating kidney dysfunction. No such abnormality was observed in BQOV treated animals. Reduced nephrotoxicity of BQOV could be due to increased catalase activity found in the kidney of BQOV treated animals and BQOV's radical scavenging activity. The data clearly demonstrates immense hypoglycemic activity and reduced toxicity of BQOV thus making the conjugate a suitable candidate for therapeutic utility.