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Effects of Protein-Free Diet and Food Deprivation on Hepatic Rhodanese Activity, Serum Proteins and Acute Cyanide Lethality in Mice^{1, 2,}

Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756

This study was undertaken to evaluate changes in hepatic and extrahepatic cyanide detoxication resulting from nutritional deficits and any parallel changes in cyanide sensitivity. Male CD-1 mice were fed control diet, control diet in reduced quantities or protein-free diet. After 14 d body weight and relative liver size were lower in the protein-free diet and the food-deprived groups than in the control group. Hepatic and serum protein and albumin concentrations were lower in the protein-free diet group and hepatic protein and albumin concentrations were higher in the food-deprived group than in the control group. Hepatic rhodanese activity was higher in the protein-free diet group than in either of the other two groups. Compared to controls lethality was higher in the protein-free diet group when cyanide was administered in doses of 4 mg/kg body weight alone and 10.7 and 16.0 mg/kg body weight after thiosulfate pretreatment; but only higher in the food-deprived group at the higher dose of cyanide given together with thiosulfate. These data suggest that hepatic rhodanese is not principally involved in the detoxication of cyanide even when exogenous thiosulfate is provided, nor does thiosulfate appear to exert its antidotal action by increasing the available cyanide-labile albumin-bound sulfane-sulfur.

KEY WORDS: • cyanide • rhodanese • albumin • diet

¹ From a thesis to be submitted by J. V. R. to the faculty of Dartmouth College in partial fulfillment of the requirements for the Doctoral degree.

² This study was supported by U.S. Public Health Service Grants ESO7104, HL14127 (R. P. S.) and CA26594 and CA32379 (B. D. R.).

³ Predoctoral Fellow of the Albert J. Ryan Foundation, Cincinnati, OH.

Manuscript received 15 June 1984.