Muscle necrosis by N-methylated p-phenylenediamines in rats: structure-activity relationships and correlation with free-radical production in vitro.
Certain derivatives of p-phenylenediamine have been shown to cause necrosis of cardiac and skeletal muscle in rats; in vitro, such compounds are known to autoxidize to the corresponding radical cations, with concomitant formation of oxygen free-radicals. In the present study, the autoxidation rates of p-phenylenediamine and its N-methyl, dimethyl, trimethyl and tetramethyl derivatives have been determined and compared with the severity of the muscle necrosis induced by each of these compounds in rats. A close correlation was observed between autoxidation rate in vitro and toxicity in vivo, suggesting that free-radical species may be involved in the initiation of the muscle damage caused by these substances.
Munday
R
R
Ruakura Animal Research Centre, Hamilton, New Zealand.
Manns
E
E
Fowke
E A
EA
Hoggard
G K
GK
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D015394:Molecular Structure; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D005609:Free Radicals; D010655:Phenylenediamines; D006861:Hydrogen Peroxide