Role of SAM-dependent thiol methylation in the renal toxicity of several solvents in mice.
The role of S-adenosylmethionine (SAM)-dependent thiol methylation in the nephrotoxicity of seven industrial solvents was studied in mice. The seven following solvents were utilized: bromobenzene (BB), styrene (STY), tetrachloroethylene (TTCE), trichloroethylene (TCE), 1,1-dichloroethylene (DCE), 1,2-dichloroethane (DCA) and hexachlorobutadiene (HCB). The experimental model comprised mice pretreated with periodate oxidized adenosine (ADOX) (100 micromol kg(-1) i.p.) 30 min before injection of solvents. In the first 4 h after ADOX treatment, the SAM levels were about fourfold higher than controls for the liver and kidney. The S-adenosylhomocysteine (SAH) levels were increased by factors of 11 and 14 and the SAM/SAH ratios were decreased by factors of 3 and 10 for the liver and kidney, respectively. These results show that ADOX treatment probably induces an inhibition of methyltransferase SAM-dependent in the liver and kidney and thus decreases the methylation capabilities. A single oral administration of BB (500 or 800 mg kg(-1)), TTCE (3500 or 4000 mg kg(-1)), TCE (3000 or 3500 mg kg(-1)) or STY (400 or 600 mg kg(-1)) did not induce renal toxicity, evaluated by the percentage of damaged tubules compared to controls. On the other hand, the three solvents DCE, HCB and DCA were nephrotoxic and the percentage of damaged tubules observed for each solvent was significantly different from the value of <1.8% for controls: 19% and 40% for DCE (130 and 200 mg kg(-1)), 50% and 46% for HCB (80 and 100 mg kg(-1)) and 5.1% and 7.6% for DCA (1000 and 1500 mg kg(-1)). The ADOX treatment in the mice did not modify the renal toxicity of the seven solvents. Thus, their renal toxicity, when it existed, was probably independent of the SAM-dependent thiolmethyltransferase activity in the mice. The results of this study are discussed from two viewpoints. The first concerns the general considerations on inhibition of thiol methyltransferase activities in mice and the second is related to the different solvents that are evoked individually.
Morel
G
G
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Ban
M
M
Hettich
D
D
Huguet
N
N
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000502:physiology*; D051379:Mice; D010084:Oxidation-Reduction; D012435:S-Adenosylhomocysteine / Q000378:metabolism / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000502:physiology*; D012997:Solvents / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism*