Role of hydrogen sulfide (H/sub 2/S) in metabolism and toxicity of cysteine S-conjugates in rat kidney
Several nephrotoxic cysteine S-conjugates are metabolized by renal cysteine conjugate ..beta..-lyase to thiols, which may release H/sub 2/S. The authors measured the rate of H/sub 2/S formation from S-conjugates with a colorimetric assay and compared the mitochondrial toxicity of H/sub 2/S and S-conjugates. H/sub 2/S formation from S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) was time- and concentration-dependent in cytosolic and mitochondrial fractions of rat kidney cortex. With 5 mM substrate, the rate of H/sub 2/S formation from CTFC was 3.9 +/- 0.5 and 12.7 +/- 3.0 nmol/min per mg protein in mitochondria and cytosol, respectively; the corresponding rates with DCVC were 1.1 +/- 0.1 and 3.7 +/- 1.3. With S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC), an extremely potent nephrotoxin, no H/sub 2/S formation was detected. Incubation of mitochondria with 1 mM DCVC or DCVHC for 2 h produced 60% and 70% inhibition, respectively, of state 3 respiration with succinate as the electron donor; with glutamate + malate or ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine as respiratory substrates, less than 20% inhibition was observed. Addition of Na/sub 2/S to respiring mitochrondria produced rapid and potent inhibition of state 3 respiration with all the above electron donors. These results show that H/sub 2/S is not a major metabolite of S-conjugates and that H/sub 2/S formation does not play a major role in S-conjugate-induced nephrotoxicity.
- Research Organization:
- Univ. of Rochester School of Medicine, NY
- OSTI ID:
- 6933308
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROGEN SULFIDES
METABOLISM
TOXICITY
RESPIRATION
INHIBITION
DOSE-RESPONSE RELATIONSHIPS
KIDNEYS
METABOLITES
MITOCHONDRIA
RATS
TIME DEPENDENCE
ANIMALS
BODY
CELL CONSTITUENTS
CHALCOGENIDES
HYDROGEN COMPOUNDS
MAMMALS
ORGANOIDS
ORGANS
RODENTS
SULFIDES
SULFUR COMPOUNDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology