Role of hydrogen sulfide (H/sub 2/S) in metabolism and toxicity of cysteine S-conjugates in rat kidney

Journal Article · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6933308

Banki, K; Elfarra, A A; Lash, L H; Anders, M W

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), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
CELL CONSTITUENTS
CHALCOGENIDES
DOSE-RESPONSE RELATIONSHIPS
HYDROGEN COMPOUNDS
HYDROGEN SULFIDES
INHIBITION
KIDNEYS
MAMMALS
METABOLISM
METABOLITES
MITOCHONDRIA
ORGANOIDS
ORGANS
RATS
RESPIRATION
RODENTS
SULFIDES
SULFUR COMPOUNDS
TIME DEPENDENCE
TOXICITY
VERTEBRATES