Metabolic effects of VO(dmpp)2 – an ex vivo1H-HRMAS NMR study to unveil its pharmacological properties

Abstract

The pharmacological action of the V(IV) compound VO(dmpp)₂ was previously evaluated in vivo using obese pre-diabetic Zucker rats treated with this compound for four weeks. Besides the promising results regarding biological parameters indicative of insulin-mimetism, a specific biological activity in mitigating impaired lipid metabolism was observed. This work aims at complementing and reinforcing data formerly attained and it represents an attempt to unveil the effect of this compound at the molecular level, particularly on the metabolic profile of different organs. Ex vivo experiments with tissue samples of the brain, liver and skeletal muscle from treated and non-treated obese Zucker rats, using lean Zucker rats as a control, were carried out by using ¹H-HRMAS. The results obtained showed that the lipid liver content, a characteristic of obese rats, significantly decreased after 4 weeks of VO(dmpp)₂ treatment, as demonstrated by the quantification of the respective signals in the ¹H-HRMAS NMR spectra. In the other analyzed tissues, the differences were not statistically significant, but a trend of a decrease of the abnormal metabolite content in treated obese rats was observed. Importantly, the therapeutic dose used showed no renal toxicity. VO(dmpp)₂ was demonstrated to be able to revert the impaired lipid metabolism in vivo and ¹H-HRMAS NMR was revealed to be a good tool to simultaneously assess the effects of a drug on the metabolic profile of different organs and tissues.