Effective control of glycemic status and toxicity in Zucker diabetic fatty rats with an orally administered vanadate compound

Abstract

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulindependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After~16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from~17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only~50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes.Key words: diabetes mellitus, tea, glycemia, type II diabetes. 894Résumé : Une nouvelle décoction de thé noir contenant du vanadate a remplacé efficacement l'insuline dans un modèle de diabète insulinodépendant chez le rat; cette décoction n'a toutefois pas été testée chez les animaux diabétiques non insulinodépendants. La décoction de thé/vanadate (TV) (contenant 30 ou 40 mg de Na-orthovanadate) a été administrée par gavage oral à des rats obèses diabétiques Zucker (D). Le Na-orthovanadate (30 mg), administré dans un excipient aqueux classique, a provoqué une diarrhée chez 50 % des rats D et la mort chez 10 %. À l'opposé, les rats traités avec TV n'ont eu aucune incidence de diarrhée ni de mortalité. Les symptômes ont été plus graves chez les deux groupes ayant reçu les plus fortes doses de vanadate, de sorte que ces doses ont été supprimées. Après environ 16 semaines, le taux de vanadium dans les extraits de plasma et de tissu a été néglig...

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

“…One of the challenges of designing metal-based drugs is to balance the potential toxicity of an active formulation with the substantial positive impact of the therapeutic aid (Thompson and Orvig 2003). 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).…”

Short-term bioaccumulation of vanadium when ingested with a tea decoction in streptozotocin-induced diabetic rats

“…The vanadium was suspended in water, and most subsequent studies continued this practice. The concentration of vanadium necessary to reduce hyperglycemia, however, was associated with some severe side effects including gastrointestinal toxicity and high mortality rates [7,10,11,14,15]. Instead of attempting to chemically modify the vanadium compound itself as has been used by many others [7][8][9]16,17], we have attempted the unconventional approach of suspending Na-orthovanadate in a tea decoction.…”

“…A lichee black tea decoction was made as described in detail [10,11]. Sodium orthovanadate (Sigma, St Louis, MO) was added to the decoction at a concentration of 20 mg vanadate per milliliter of tea decoction.…”

“…Instead of suspending the vanadate in water as is used conventionally, it has been suspended in a lichee black tea decoction [10,11]. Insulin-deficient and insulin-resistant diabetic rats treated with this compound have been effectively maintained at nondiabetic glucose levels for up to 3 months with either reduced toxicity, or no side effects or toxicity [10,11]. The mechanism whereby the tea decoction protects against the toxic side effects of vanadate is unclear.…”

Oxidovanadium(IV) sulfate-induced glucose uptake in HepG2 cells through IR/Akt pathway and hydroxyl radicals

“…Vanadium and its compounds stimulate glucose transport and oxidation [5][6][7], and glycogen synthesis [8,9]. Moreover, some vanadium compounds have been previously documented to have insulin-like effects in streptozotocin (STZ)-diabetic rats [10].…”