Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Abstract

■ AbstractOrganic vanadium compounds offer several advantages in the treatment of diabetes, yet they are impractical to use because of known side effects. In order to ameliorate the side effects of vanadium, we conjugated it with quercetin to form bis(quercetinato)oxovanadium IV (BQOV). This study evaluates the effect of BQOV treatment on carbohydrate metabolism and overall oxidative stress in streptozotocininduced (STZ) diabetic mice. Administration of BQOV orally to diabetic mice for 3 weeks led to a reduction of blood glucose levels and the animals exhibited normal glucose tolerance at the end of the study period. The increase in glucose uptake by skeletal muscle and liver as well as the normalization of mRNA levels of G-6-Pase and glucokinase in the liver after BQOV treatment pointed to improvements in carbohydrate metabolism. The analysis of the antioxidant status of serum, liver and pancreas revealed reduced oxidative stress in BQOV-treated animals compared to untreated diabetic controls. Serum analyses for kidney and liver function showed that BQOV treatment provoked total protection of the kidney and partial protection of the liver from diabetogenic insults. The number of insulin-positive cells and the amount of pancreatic insulin in treated mice (1.2038 ± 0.34 ng/mg tissue) did not account for pancreatic regeneration but suggested an insulin-mimetic action on the part of BQOV. Moreover, administration of BQOV for 3 weeks did not show any visible side-effects. This data indicate that BQOV is a safe and potent agent for diabetes treatment, because it is able to improve carbohydrate metabolism and to reduce overall oxidative stress.

Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress

“…Previous studies on animal models support this interpretation, including: (i) antioxidants (either co-administration [26,27] or incorporation of antioxidant as coordination ligands [25]) significantly decrease vanadium toxicity; (ii) therapeutic dose of VO(acac) 2 [47] and VOdipic [48] produced 10-30 lM (serum) and <1 lM (liver and muscles) of vanadium without marked toxicity which is consistent with the concentrations of vanadyl complexes needed for mitochondrial PTP activation (Figs. 2-4); and (iii) decavanadate is 100-fold more potent than metavanadate in inhibiting mitochondrial functions, but decavanadate treatments were less toxic than those of metavanadate [46].…”

“…Many studies suggested a close relationship between vanadium toxicity and ROS [9,[20][21][22]. Vanadium induced apoptosis of cells associated with elevated ROS levels and ROS-related signal transduction [23,24], while antioxidants, either as complex ligands [25] or co-administration [26,27], significantly reduced vanadium toxicity. Stimulation of ROS production by vanadium varied depending on redox activity of vanadium species [9,28].…”

Protective Effects of Quercetin on Hyperglycemia and Stress Proteins Expression in Rats with Streptozocin-Induced Diabetes

“…Information regarding the effects of quercetin on the expression of enzymes involved in glucose metabolism is limited; however, Jung et al (2006) previously showed that flavonoid hesperidin and naringin significantly increased the expression of GK, and naringin decreased the expression of phosphoenol pyruvate carboxykinase and G6P in the liver of diabetic mice (28). The effects of bis (quercetinato) oxovanadium IV (BQOV) on normalizing the expression of G6P and GK in the liver of mice with STZ-induced diabetes were also demonstrated by Shukla et al (2007) (29). Furthermore, Vessal et al (2003) has previously reported that hepatic GK activity was increased by quercetin treatment (20).…”

A new salicylic acid-derivatized kojic acid vanadyl complex: Synthesis, characterization and anti-diabetic therapeutic potential

“…Previously, direct coordination of vanadyl ions with natural antioxidants produced novel complexes such as bis (quercetinato)oxovanadium(IV) (BQOV) [20,21] and bis[curcumino] oxovanadium (BCOV) [22]. BQOV was shown to improve carbohydrate metabolism and to reduce overall oxidative stress [20,21]; BCOV was shown to improve the cardiovascular complications associated with diabetes [22].…”