Muscle necrosis by N-methylated p-phenylenediamines in rats: Structure-activity relationships and correlation with free-radical production in vitro

Munday, Rex; Manns, E.; Fowke, E.A.; Hoggard, G.K.

doi:10.1016/0300-483x(89)90118-2

Cited by 28 publications

(12 citation statements)

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“…5,23 The histological changes observed in the muscles of rats treated with this substance, and the accompanying elevations of plasma enzyme activities, were very similar to those observed with other myotoxic polyaminobenzenes. [1][2][3] 2,3,6-Triaminopyridine was much less toxic to the heart than to skeletal muscle. In this respect, it resembles ring-methylated p-phenylenediamines 3 rather than 1,2,4-triaminobenzene and N-methylated p-phenylenediamines, which cause a similar degree of necrosis in both cardiac and skeletal muscle.…”

Section: Discussionmentioning

confidence: 92%

“…Aromatic polyamines such as 1,2,4-triaminobenzene (I) and the N-methyl and ring-methyl derivatives of p-phenylenediamine (II) are selectively toxic to striated muscle in animals. [1][2][3] These compounds form unusually stable free radicals and readily autoxidize at neutral pH, generating superoxide radical and other 'active oxygen' species. [2][3][4] Such substances are also selectively oxidized by the cytochrome c/cytochrome oxidase system of mitochondria, establishing alternative pathways for electron transport in the respiratory chain with concomitant disruption of mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] These compounds form unusually stable free radicals and readily autoxidize at neutral pH, generating superoxide radical and other 'active oxygen' species. [2][3][4] Such substances are also selectively oxidized by the cytochrome c/cytochrome oxidase system of mitochondria, establishing alternative pathways for electron transport in the respiratory chain with concomitant disruption of mitochondrial function. 5 It has been suggested 5 that effects on mitochondrial energy production, together with free radical formation, are responsible for the myotoxic activity of such polyamines.…”

Section: Introductionmentioning

confidence: 99%

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2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine, causes muscle necrosis and renal damage in rats

Munday

Manns

1998

J. Appl. Toxicol.

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Some aromatic polyamines form very stable free radicals and readily undergo autoxidation with concomitant formation of ‘active oxygen’ species. These substances cause necrosis of striated muscle in rats, and it has been suggested that this is due to free radical formation and disruption of energy production through their oxidation via the cytochrome c/cytochrome oxidase system of mitochondria. 2,3,6‐Triaminopyridine, which is structurally related to the myotoxic amines and likewise undergoes autoxidation and disrupts mitochondrial metabolism, is a metabolite of the widely used urinary analgesic phenazopyridine. When administered to rats, triaminopyridine caused extensive necrosis of skeletal muscle and a lesser degree of damage to heart muscle. It also induced vacuolation and necrosis of distal tubules of the kidney, associated with tubular dilatation and cast formation. Both muscle damage and renal tubular necrosis have been reported following use or abuse of phenazopyridine, and it is likely that triaminopyridine is responsible for both of these effects. © 1998 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine, causes muscle necrosis and renal damage in rats

Munday

Manns

1998

J. Appl. Toxicol.

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“…It has been reported that free radicals are associated with the onset of skeletal muscle atrophy [50][51][52]. Additionally, polyamines have been shown to provide protection against free radicals [53][54][55][56][57][58], potentially in conjunction with the endogenous antioxidant glutathione (GSH/ GSSG).…”

Section: Discussionmentioning

confidence: 99%

Effect of Hindlimb Suspension and Clenbuterol Treatment on Polyamine Levels in Skeletal Muscle

Abukhalaf

Deutsch²,

Wineski³

et al. 2002

Pharmacology

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Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol’s action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy.

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“…Munday et coll. [8] ont constaté après une injection en sous-cutanée de la p-PD chez le rat une nécrose musculaire de sévérité variable touchant le diaphragme et la langue. Dans une autre étude chez le rat [9] une rhabdomyolyse aiguë avec nécrose segmentaire des myofibrilles, une prolifération des cellules satellites et une infiltration par des macrophages ont été observées à la 72 e heure.…”

Section: Introductionunclassified

Induction d’apoptose par la p-Phénylènediamine dans un myélome murin

et al. 2011

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Résumé -Objectif : Les mécanismes de toxicité et de génotoxicité induits par la Para-phénylèneDiamine (p-PD), un composant de la teinture pour cheveux suspecté d'être carcinogène, sur des cellules tumorales murines, type P3X63Ag8.653 ont été étudiés. Méthodes : L'effet de la p-PD sur la viabilité et celui sur la prolifération cellulaire ont été évalués par la méthode d'exclusion du bleu de trypan. Son effet sur l'ADN des cellules P3X63Ag8.653 a été analysé après une extraction d'ADN et une électrophorèse sur gel d'agarose puis confirmé par la technique TUNEL en cytométrie en flux. Résultats : Un blocage de la prolifération avec diminution de la viabilité cellulaire ont été observés. La fragmentation de l'ADN dose-dépendante témoignant de l'effet apoptotique a été détectée sur gel d'agarose et confirmée par cytométrie en flux (technique TUNEL). Conclusion : Les résultats obtenus montrent que la p-PD induit in vitro un blocage de la prolifération cellulaire et une apoptose dose-dépendante des cellules tumorales murines.Mots clés : Para-phénylèneDiamine (p-PD), apoptose, cellules tumorales murines, toxicité, teinture capillaire Abstract -Aims: The mechanism of toxicity and genotoxicity of p-Phenylenediamine (p-PD), a component of human permanent hair dye and suspected to be a carcinogen, on the growth of murine tumor cells (P3X63Ag8.653) was investigated. Methods: The effect of p-PD on cell viability and proliferation was evaluated by the trypan blue exclusion method. The effect on the P3X63Ag8.653 cell DNA was analyzed by gel electrophoresis and confirmed by flow cytometry analysis (TUNEL technique). Results: A dose-dependent DNA fragmentation analyzed by gel electrophoresis shows a strong correlation with the flow cytometry analysis (TUNEL technique), suggesting that the effect of p-PD on overall viability and proliferation is mediated by DNA damage and an increase in apoptosis. Conclusion: The results suggest that the effect of p-PD on overall viability and proliferation of murine tumor cells is mediated by DNA damage and an increase in apoptosis in a dose-dependent manner.

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Muscle necrosis by N-methylated p-phenylenediamines in rats: Structure-activity relationships and correlation with free-radical production in vitro

Cited by 28 publications

References 31 publications

2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine, causes muscle necrosis and renal damage in rats

2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine, causes muscle necrosis and renal damage in rats

Effect of Hindlimb Suspension and Clenbuterol Treatment on Polyamine Levels in Skeletal Muscle

Induction d’apoptose par la p-Phénylènediamine dans un myélome murin

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