The biomimetic [Cr3O[O2CCH2CH3)(6)(H2O](3)](+) decreases plasma cholesterol and triglycerides in rats: towards chromium-containing therapeutics

The in vivo effects of administration of the synthetic, functional biomimet ic [Cr3O(O2CCH2CH3)(6) (H2O)(3)](+) 1 and a naturally occurring, biological ly active form of chromium, low-molecular-weight chromium-binding substance (LMWCr), to rats are described. Given that the complexes are proposed to f unction by interacting with insulin receptor, trapping it in its active con formation, in contrast to current chromium-containing nutrition supplements , which only serve as sources of absorbable chromium, changes in lipid and carbohydrate metabolism would be expected. After 12 weeks administration (2 0 mu g/kg body mass), compound 1 results in 40% lower levels of blood plasm a LDL cholesterol, 33% lower levels of total cholesterol, and significantly lower HDL cholesterol and triglyceride; these results are in stark contras t to those of administration of other forms of Cr(III) to rats, which have no effect on these parameters. LMWCr, in contrast to 1, has no effect as it probably is degraded in vivo or excreted. These results are interpreted in terms of the mechanism of chromium action in response to insulin and the a ctivation of insulin receptor, and the potential for the rational design of chromium-containing therapeutics is discussed.