title: Chromium-induced excretion of urinary lipid metabolites, DNA damage, nitric oxide production, and generation of reactive oxygen species in Sprague-Dawley rats.
abstract: Chromium and its salts induce cytotoxicity and mutagenesis, and vitamin E has been reported to attenuate chromate-induced cytotoxicity. These observations suggest that chromium produces reactive oxygen species which may mediate many of the untoward effects of chromium. We have therefore examined and compared the effects of Cr(III) (chromium chloride hexahydrate) and Cr(VI) (sodium dichromate) following single oral doses (0.50 LD50) on the production of reactive oxygen species by peritoneal macrophages, and hepatic mitochondria and microsomes in rats. The effects of Cr(III) and Cr(VI) on hepatic mitochondrial and microsomal lipid peroxidation and enhanced excretion of urinary lipid metabolites as well as the incidence of hepatic nuclear DNA damage and nitric oxide (NO) production were also examined. Increases in lipid peroxidation of 1.8- and 2.2-fold occurred in hepatic mitochondria and microsomes, respectively, 48 hr after the oral administration of 25 mg Cr(VI)/kg, while increases of 1.2- and 1.4-fold, respectively, were observed after 895 mg Cr(III)/kg. The urinary excretion of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) were determined at 0-96 hr after Cr administration. Between 48 and 72 hr post-treatment, maximal excretion of the four urinary lipid metabolites was observed with increases of 1.5- to 5.4-fold in Cr(VI) treated rats. Peritoneal macrophages from Cr(VI) treated animals 48 hr after treatment resulted in 1.4- and 3.6-fold increases in chemiluminescence and iodonitrotetrazolium reduction, indicating enhanced production of superoxide anion, while macrophages from Cr(III) treated animals showed negligible increases. Increases in DNA single strand breaks of 1.7-fold and 1.5-fold were observed following administration of Cr(VI) and Cr(III), respectively, at 48 hr post-treatment. Enhanced production of NO by peritoneal exudate cells (primarily macrophages) was monitored following Cr(VI) administration at both 24 and 48 hr post-treatment with enhanced production of NO being observed at both timepoints. The results indicate that both Cr(VI) and Cr(III) induce an oxidative stress at equitoxic doses, while Cr(VI) induces greater oxidative stress in rats as compared with Cr(III) treated animals.
authors.affiliation: Department of Pharmaceutical Sciences, Creighton University, Omaha, NE 68178, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bagchi
authors.forename: E A
authors.initials: EA
authors.lastname: Hassoun
authors.forename: M
authors.initials: M
authors.lastname: Bagchi
authors.forename: S J
authors.initials: SJ
authors.lastname: Stohs
mesh_terms: D000079:Acetaldehyde / Q000652:urine; D000096:Acetone / Q000652:urine; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D002840:Chromates / Q000008:administration & dosage / Q000633:toxicity*; D017608:Chromium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D005260:Female; D005557:Formaldehyde / Q000652:urine; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000652:urine*; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000652:urine; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D002712:Chlorides; D002840:Chromates; D017608:Chromium Compounds; D004277:DNA, Single-Stranded; D008055:Lipids; D017382:Reactive Oxygen Species; D013481:Superoxides; D000096:Acetone; D005557:Formaldehyde; D009569:Nitric Oxide; D008315:Malondialdehyde; C016104:sodium bichromate; C017133:chromous chloride; D000079:Acetaldehyde