TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 2362. HEALTH EFFECTSglutathione complexes have been shown to form DNA adducts. Reduction by ascorbate leads tochromium(III), but chromium(V) has been generated by the reaction of chromium(VI) with riboflavin(vitamin B 2 ) and ribose derivatives (De Flora and Wetterhahn 1989). Reaction of chromium(VI) withhydrogen peroxide has led to the formation of chromium(V) complexes and hydroxyl radicals (Aiyar etal. 1991). Other important intracellular reduction reactions of chromium(VI) involve enzyme-catalyzedand NADPH-dependent mechanisms. Microsomal reduction of chromium(VI) by cytochrome P450 tochromium(III) may involve the transient formation of chromium(V) (De Flora and Wetterhahn 1989).Hojo and Satomi (1991) examined the toxicity of potassium dichromate(VI) (0.6 mmol chromium/kg),potassium tetraperoxochromate(V) (1.0 mmol/kg), green chromium(V)-glutathione complex(1.0 mmol/kg), and chromium nitrate (III) (0.6 mmol/kg) on kidneys of male ddY mice (6 animals perdose group). Twenty-four hours after injections, mice were sacrificed and changes in kidney weight andfunction were assessed. Chromium(VI) resulted in a 10.7%±2.7 decrease in body weight, a 2-foldincrease in serum urea nitrogen, a decrease in kidney nonprotein sulfhydryl contents (3.3±0.1 versuscontrol values of 3.7±0.1) and a decrease of kidney-glutathione reductase activity from a control value of17.4±1.5 to 14.1±1.3 U/g. Potassium tetraperoxochromate(V) treatment resulted in 50% of the animalsdying. Body weights and kidney-glutathione reductase activity were much lower than for animals treatedwith chromium(VI), and serum urea levels were 102.9±17.7 mg/dL, which is about twice that observed inanimals treated with chromium(VI). The chromium(V) glutathione complex was much less toxic andshowed values that were similar or close to control values. Pretreatment with 10 mmol/kg glutathionemethyl ester in the chromium(VI)-treated animals appeared to reduce the body weight loss and caused theserum urea levels to be normal. Butathione sulfoximine (an inhibitor of glutathione synthesis) greatlyenhanced the levels of serum urea, loss of glutathione reductase activity and decrease in kidneynonprotein sulfhydryl groups. Butathione sulfoximine pretreatment resulted in one of the six animalsdying. Animals treated with chromium(III) experienced weight loss, but other parameters were notmarkedly changed from control values. Pretreatment with butathione sulfoximine in animals treated withchromium(III) only caused a decrease in kidney nonprotein sulfhydryl groups. The authors indicated thatwith excess levels of glutathione, chromium(VI) is more readily reduced to chromium(III), whereas atlower levels of glutathione the reduction process is slower, resulting in slower reduction of the more toxicintermediate chromium(V). Also, at higher concentrations of glutathione, chromium(V)-glutathionecomplexes may form which may prevent chromium(V) from reacting at target sites that elicit toxicresponses.