Synthesis, structural properties and insulin-enhancing potential of bis(quercetinato)oxovanadium(IV) conjugate

Shukla, Ruchi; Barve, Vivek; Padhyé, Subhash; Bhonde, Ramesh

doi:10.1016/j.bmcl.2004.07.020

Cited by 40 publications

(17 citation statements)

References 31 publications

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“…The present investigation evaluates the effect of the recently reported organic vanadium compound, BQOV [12] on glycemic status, carbohydrate metabolism and oxidative stress in STZ-diabetic mice. Oral administration of BQOV for 3 weeks led to a reduction in blood glucose, a normalization of carbohydrate metabolism and an overall reduction in oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

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

Shukla

Padhyé²,

Modak³

et al. 2007

Rev Diabet Stud

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■ 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.

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Section: Discussionmentioning

confidence: 99%

“…In an effort to increase gastrointestinal absorption and reduce the toxicity of vanadium we have conjugated a flavonoid, quercetin with vanadium and synthesized BQOV [12]. The conjugate has immense hypoglycemic potential and has been found to be much less toxic than the parent vanadium salt in both in vitro and in vivo studies [13].…”

Section: Introductionmentioning

confidence: 99%

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

Shukla

Padhyé²,

Modak³

et al. 2007

Rev Diabet Stud

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“…Fine chemicals like quercetin, streptozotocin, DCFH-DA, propidium iodide, DMSO, RNaseA and proteinase K were purchased from Sigma. VOSO 4 was purchased from Thomas Baker while BQOV was prepared according to the method described earlier (Shukla et al 2004). …”

Section: Generalmentioning

confidence: 99%

“…Recently several researchers have taken up a combinatorial approach wherein they combine vanadium treatment regime with another antidiabetic agent like Trigonella foenum graecum (Preet et al 2005) or antioxidant like black tea decoction (Clark et al 2004) so as to reduce its toxicity without compromising its antidiabetic potential. In order to circumvent the aforementioned ill effects of vanadium we have synthesized vanadium-quercetin conjugate (bis(quercetinato)oxo vanadium (IV), BQOV) (C 32 H 30 O 24 SV 2 ) which has been proved to be an effective oral hypoglycemic agent (Shukla et al 2004). Further we have hypothesized that quercetin (a strong antioxidant) would combat prooxidant nature of vanadium and make BQOV much less toxic than its parent vanadium salt, VOSO 4 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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.

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“…34) Other interesting antidiabetic vanadyl complexes with different coordination environments, such as porphyrin complexes, thiazolethione complexes, hydroxydiazine-type complexes, furan complex, quercetin-related complexes, salen-related complexes, and dinuclear complexes, have recently been proposed. 14,[35][36][37] Zinc Type 2 insulin-resistant DM accounts for 95% of all DM. The therapy for type 2 DM relies mainly on several chemotherapies to reduce hyperglycemia in addition to diet control and exercise.…”

Section: Vanadiummentioning

confidence: 99%

Overview and Frontier for the Development of Metallopharmaceutics

Sakurai

2010

JOURNAL OF HEALTH SCIENCE

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This review introduces the development of metal-containing pharmaceutics (metallopharmaceutics) such as anticancer agents containing platinum (Pt) and ruthenium (Ru), and superoxide dismutase (SOD) mimetic, focusing on the recent topics on antidiabetic vanadium (V) and zinc (Zn) complexes as well as antioxidative copper (Cu) and Zn complexes. From the ancient ages, people used many types of inorganic compounds to treat physical disorders or diseases. Since the modern concept of chemotherapy was achieved by Paul Ehrlich, who developed the arsenic (As)-containing compound to treat syphilis in 1910, a wide variety of metallopharmaceutics have been proposed and clinically used worldwide. This review is described for the researchers who are interested in the current states for the development of metallopharmaceutics.

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Synthesis, structural properties and insulin-enhancing potential of bis(quercetinato)oxovanadium(IV) conjugate

Cited by 40 publications

References 31 publications

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

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

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

Overview and Frontier for the Development of Metallopharmaceutics

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