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 VOSO(4) 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, VOSO(4) also caused higher necrosis. Hypoglycemic potential of VOSO(4) and BQOV was tested in streptozotocin-induced diabetic Balb/c mice. A marked difference was observed in the hypoglycemic action of VOSO(4) and BQOV treated mice that lasted only for about 6 h in VOSO(4) 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 VOSO(4) 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.
Shukla
Ruchi
R
Tissue Engineering and Banking Laboratory, National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.
Barve
Vivek
V
Padhye
Subhash
S
Bhonde
Ramesh
R
D000818:Animals; D000975:Antioxidants / Q000032:analysis; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D023382:Toxicity Tests, Acute; D017968:Vanadium Compounds / Q000627:therapeutic use / Q000633:toxicity*
D000975:Antioxidants; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D017968:Vanadium Compounds; C517295:bis(quercetinato)oxovanadium(IV); C034028:vanadyl sulfate; D011794:Quercetin