The metabolism of sulfite in liver. Stimulation of sulfate conjugation and effects on paracetamol and allyl alcohol toxicity.
Sulfite is rapidly oxidized to sulfate in the liver. This was shown both in isolated rat hepatocytes and isolated perfused liver. In addition sulfite treatment resulted in release of GSH originating probably from low molecular disulfides such as GSSG and/or mixed disulfides between GSH and protein sulfhydryl groups. Sulfite was demonstrated to be an efficient precursor for sulfate conjugation. This was demonstrated using paracetamol as a substrate. Sulfite was even more efficient in supplying sulfate for sulfate conjugation than inorganic sulfate. Sulfite was furthermore shown to be protective against the toxicity of both N-acetyl-p-benzoquinone imine (NAPQI), the reactive paracetamol metabolite, and acrolein, a reactive aldehyde which is a metabolite of allyl alcohol. This protection is most likely due to direct reaction between sulfite and these reactive metabolites in a manner similar to that occurring with GSH and other thiols. When NAPQI and acrolein were generated intracellularly in isolated hepatocytes from paracetamol and allyl alcohol, respectively, toxicity was also expressed. In this case sulfite only protected against allyl alcohol induced toxicity and not against paracetamol induced toxicity. The reason for this discrepancy is not clear but may depend on factors such as site of generation of the reactive metabolite or the reactivity of the reactive metabolite.
Sun
Y P
YP
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Cotgreave
I
I
Lindeke
B
B
Moldéus
P
P
D000433:1-Propanol / Q000633:toxicity; D000082:Acetaminophen / Q000633:toxicity*; D000171:Acrolein / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D020005:Propanols; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism*; D013447:Sulfites / Q000378:metabolism* / Q000493:pharmacokinetics
D020005:Propanols; D013431:Sulfates; D013447:Sulfites; D000082:Acetaminophen; C006463:allyl alcohol; D000171:Acrolein; D000433:1-Propanol; D005978:Glutathione