Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in both insulin secretion and/or insulin action. Hyperglycemia, the primary clinical manifestation of diabetes mellitus, is associated with non enzymatic glycation of proteins and free radicals generation.1,2) These processes can cause protein cross-linking and damage in other biomolecules such as enzymes, lipids and DNA; contributing to the overall complications of diabetes mellitus.
3-7)d-Aminolevulinate dehydratase (d-ALA-D) is a sulfhydrylcontaining enzyme, involved in the formation of porphobilinogen, a heme precursor.8) d-ALA-D activity is highly sensitive to the presence of a variety of pro-oxidant agents and to situations associated with oxidative stress, which oxidize its -SH groups.9,10) Of note, in diabetic state the activity of d-ALA-D and the other enzymes of heme pathway are significantly inhibited.11,12) Consistent with these findings it has been reported that high levels of glucose also produce chemical alterations in other physiologically abundant proteins such as collagen, hemoglobin and albumin. 13,14) Thus, the interest in compounds that could potentially reduce the biological alterations associated with hyperglycemia is intense.Selenium is known to be an essential trace element that plays a crucial role as an integral component of several enzymes with antioxidant properties, including glutathione peroxidase. 15,16) Conversely, high doses of selenium can be toxic via its ability to catalyze the oxidation of thiols and to generate free radicals. 10,17) Of particular importance, this element because of its physiological antioxidant properties, exhibits a number of potentially beneficial effects against the development of different diseases 10,[18][19][20] including diabetes mellitus. [21][22][23][24] Moreover, the literature data have indicated that inorganic selenium compounds can attenuate the cytotoxic effects of hyperglycemia via its insulin-mimetic and anti-glycating properties. 25,26) On the other hand, data reported in the literature indicating the therapeutic benefit of synthetic organoselenium compounds in the treatment of diabetes are rare. 24,27,28) Diphenyl diselenide is the simplest of the diaryl diselenides and has glutathione peroxidase-like activity, exhibits antioxidant, hepatoprotective, antiulcer and anti-inflammatory properties.10,29,30) Importantly, a previous study from our research group showed that chronic administration of diphenyl diselenide, at low doses, reduces temporarily the hyperglycemia in streptozotocin-treated (STZ-treated) rats.
23)Thus, the aim of this study was to investigate whether acute treatment with diphenyl diselenide could ameliorate the diabetogenic effects induced by alloxan administration. Thereby, we examined the effect of diphenyl diselenide treatment before and after the diabetes induction, in order to determinate if the compound would act by preventing (pretreatment) and/or restoring (post-treatment) alloxan toxicity. Furthermore, the analy...