Experimental work in our laboratory has confirmed the protective activity of
vanadium compounds on
hyperglycemia and
glycosuria in
streptozotocin (STZ) diabetes. Furthermore, diabetic
cataract has also been partially prevented. Nevertheless, the combination of a natural
antioxidant,
vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and
vanadate, with the purpose of eliciting the best possible
antidiabetic protection. More recently, a
lipid soluble synthetic
antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against
brain injury and
ischemia. This compound inhibits the
iron-dependent lipid peroxidation 100 times more effectively than
vitamin E. This investigation has introduced a combination of the
vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer,
U-83836E, in order to improve the insufficient protection when
vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in
drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces,
glycosuria and
proteinuria were determined on
biological samples obtained in metabolic cages;
body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye
lenses was controlled and registered. At the end of the experiment, circulating
glycosylated hemoglobin (HbA1c),
fructosamine,
N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent
peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by
vanadate alone. At subsequent steps,
U-83836E significantly improved the protective effect of
vanadate alone on
polydipsia and
polyuria, but especially on
hyperglycemia and
glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the
cataract. In conclusion, these findings demonstrate that the lazaroid
U-83836E succeeds in further protecting the most important symptoms of diabetes treated with
vanadate, and that this
antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.