Studies on the muscle toxicant 2,3,5,6-tetramethyl p-phenylenediamine: effects on various biomarkers including urinary creatine and taurine.
The effect of the specific muscle toxicant, 2,3,5,6-tetramethyl p-phenylenediamine (TMPD), on urinary creatine and taurine, markers of testicular and liver dysfunction, respectively, has been investigated in male Sprague-Dawley rats. Damage to the gastrocnemius and soleus muscles was accompanied by a rise in serum creatine kinase (predominantly the muscle-specific isoenzyme, CK-MM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Increases in serum alpha-hydroxybutyrate dehydrogenase (HBDH) and total lactate dehydrogenase (LDH) (mainly isoenzymes, LDH1 and LDH2), occurred but only minor damage to the heart and no rise in CK-MB, (heart muscle isoenzyme) was seen. Damage to stage XIV tubules in the testis was evident histologically after the highest dose. This was accompanied by an increase in LDH-C4 testis-specific isoenzyme and a decrease in serum testosterone. Apart from reduced serum albumin, no other serum parameters indicated liver damage and there was only slight liver steatosis in some animals at the highest dose. Urinary taurine was not significantly raised after any dose of TMPD, but there was a significant increase in urinary creatine after the highest dose. It can be concluded that in the presence of discrete muscle damage, the use of urinary taurine and urinary creatine as markers of liver and testicular dysfunction, respectively, is not confounded. However, a variety of different markers should be used in conjunction to fully delineate the tissue damage due to toxic chemicals.
Draper
R P
RP
Department of Toxicology, School of Pharmacy, University of London, UK.
Waterfield
C J
CJ
York
M J
MJ
Timbrell
J A
JA
D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D003401:Creatine / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology; D009336:Necrosis; D010655:Phenylenediamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000652:urine*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D010655:Phenylenediamines; D013654:Taurine; D013739:Testosterone; D003401:Creatine