ABSTRACT
Chromium picolinate, [Cr(pic)(3)], is a popular nutritional supplement found in a variety of consumer products. Despite its popularity, safety concerns over its use have arisen. The supplement has been shown to generate clastogenic damage, mitochondrial damage, oxidative damage, and mutagenic effects in cultured cells and oxidative DNA damage and lipid peroxidation in rats. Recently [Cr(pic)(3)] has been demonstrated to generate heritable genetic change and delays in progeny development in Drosophila melanogaster. Based on the damage to chromosomes of cultured cells and of animal models, similar chromosome damage appeared to be a likely source of the mutagenic effects of the supplement in Drosophila. The current three-part study examines the effects of several chromium-containing supplements and their components on hatching and eclosion rates and success of development of first generation progeny of adult Drosophila fed food containing these compounds. It further examines the effects of the compounds on longevity of virgin male and female adults. Finally, the chromosomes in the salivary glands of Drosophila late in the third instar larval stage, which were the progeny of Drosophila whose diets were supplemented with nutritional levels of [Cr(pic)(3)], are shown to contain on average over one chromosomal aberration per two identifiable chromosomal arms. No aberrations were observed in chromosomes of progeny of untreated flies. The results suggest that human consumption of the supplement should be a matter of concern and continued investigation to provide insight into the requirements of chromium-containing supplements to give rise to genotoxic effects.
Subject(s)
Chromium Compounds/toxicity , Chromosome Aberrations/chemically induced , Drosophila melanogaster/drug effects , Picolinic Acids/toxicity , Animals , Chromium Compounds/administration & dosage , Chromium Compounds/chemistry , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Female , Longevity/drug effects , Male , Ovum/drug effects , Picolinic Acids/administration & dosage , Picolinic Acids/chemistryABSTRACT
The nutritional dietary supplement chromium picolinate, [Cr(pic)(3)], has gained much notoriety as a safe supplement that supposedly promotes fat loss and muscle enhancement in humans. Thus, a significant industry has materialized around the incorporation of [Cr(pic)(3)] in many sports foods and drinks and a variety of weight loss products. However, in vitro studies have suggested that low levels of [Cr(pic)(3)] in the presence of biological reducing agents can catalytically generate reactive oxygen species, and recent in vivo studies have detected oxidative damage in rats receiving the supplement. The potential deleterious in vivo effects of this activity were examined by using Drosophila melanogaster. [Cr(pic)(3)], but not CrCl(3), at levels of 260 microg Crkg food or less were found to lower the success rate of pupation and eclosion and to arrest development of pupae in a concentration dependent fashion. X-linked lethal analysis indicates that the supplement greatly enhances the rate of appearance of lethal mutations and dominant female sterility.
Subject(s)
Dietary Supplements/toxicity , Drosophila melanogaster/genetics , Genes, Lethal , Infertility, Female/chemically induced , Infertility, Male/chemically induced , Oviposition/drug effects , Picolinic Acids/toxicity , X Chromosome , Animals , Drosophila melanogaster/growth & development , Ethyl Methanesulfonate , Female , Infertility, Female/genetics , Infertility, Male/genetics , Male , Mutagenesis , Picolinic Acids/administration & dosage , Pupa/drug effectsABSTRACT
Chromium picolinate, [Cr(pic)(3)], is a popular nutritional supplement; however, the fate of the complex in vivo has not previously been established. Consequently, rats were administered [51Cr(pic)(3)] intravenously and the fate of the radiolabel in the urine, blood plasma, tissues, and subcellular components of hepatocytes was followed for the first 24 h after injection. The supplement leaves the blood stream rapidly appearing in the urine and entering tissue cells intact. Kidney, muscle, and liver possess most of the absorbed radiolabel. In hepatocytes, the radiolabel appears most rapidly in the nucleus and mitochondria, then in the cytosol, and finally in the lysosomes and microsomes. Thus, while the lifetime of the supplement in vivo is brief, it enters cells rapidly intact. The significance of the lifetime and distribution of [Cr(pic)(3)] in relationship to recent reported potential DNA damage from the supplement is discussed.
Subject(s)
Picolinic Acids/pharmacokinetics , Subcellular Fractions/metabolism , Animals , Chromatography, Gel , Liver/metabolism , Male , Picolinic Acids/blood , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
Chromium picolinate, [Cr(pic)(3)], is the second most popular nutritional supplement after calcium supplements. However, the supplement, unlike simple inorganic Cr(III) salts, has been shown in the presence of biological reducing agents in vitro to catalytically generate appreciable quantities of hydroxyl radicals, resulting in DNA damage. The complex has also been shown to be remarkably stable in vitro at neutral, basic, or weakly acidic pHs. Thus, the significance of this ability to generate hydroxyl radicals depends on whether the complex is absorbed by cells intact along with the stability and concentration of the complex in cells. Consequently, male Sprague Dawley rats have been injected with (51)Cr- and (3)H-labeled [Cr(pic)(3)]. The tissue distribution, urinary and fecal loss, and subcellular hepatocyte distribution and concentration of the labels suggest that [Cr(pic)(3)] has a lifetime of less than 1 day in vivo, minimizing the potential threat from the supplement itself.
