Molecular Basis of the Biological Function of Molybdenum. The Relationship between Sulfite Oxidase and the Acute Toxicity of Bisulfite and SO2

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 70; no. 12; pp. 3655 - 3659
• Main Authors: Cohen, Harvey J., Drew, Robert T., Johnson, Jean L., Rajagopalan, K. V.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.12.1973; National Acad Sciences
• Subjects: Animals; Biological Sciences: Biochemistry; Biotransformation; Deficiency Diseases - enzymology; Deficiency Diseases - metabolism; Dosage; Dose-Response Relationship, Drug; Enzymes; Lethal dose 50; Liver; Liver - enzymology; Male; Molybdenum; Oxidases; Oxidoreductases - metabolism; Rats; Sulfites; Sulfites - metabolism; Sulfites - toxicity; Sulfur Dioxide - metabolism; Sulfur Dioxide - toxicity; Tungsten; Tungsten - pharmacology; Xanthine Oxidase - metabolism; Xanthines
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.70.12.3655

The administration of tungsten to rats maintained on a low molybdenum diet resulted in a dose- and time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC 1.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHSO3per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats. The survival time of rats exposed to SO2at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO2. At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO2, death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO2. Respiratory death probably results from the toxicity of gaseous SO2before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO2.