Effects of selected chemicals on the glutathione status in the male reproductive system of rats

Abstract

Previous studies have suggested a significant role for reproductive tract glutathione in protecting against chemical-induced germ-cell mutations. Therefore, a number of compounds were tested for their ability to perturb glutathione levels in the testes and epididymides as well as liver following single acute dosages to rats. Phorone (250 mg/kg), isophorone (500 mg/kg), and diethyl maleate (500 mg/kg) significantly reduced glutathione in the liver and in both reproductive organs examined. Methyl iodide (100 mg/kg), trimethyl phosphate (600 mg/kg), naphthalene (500 mg/kg), acetaminophen (1500 mg/kg), and pentachlorophenol (25 mg/kg) affected hepatic and epididymal glutathione, but had little or no effect on testicular levels. The ability of isophorone to enhance the covalent binding of tritiated ethyl methanesulfonate (3H-EMS) to spermatocytes was assessed. Perturbation of reproductive tract glutathione by isophorone treatment significantly enhanced the extent of 3H-EMS-induced binding to sperm heads. The temporal pattern of ethylations in sperm heads was consistent with the stage of sperm development known to be susceptible to ethylations by EMS. Therefore, chemical-induced lowering of glutathione in the male reproductive tract may be a mechanism for potentiation of chemical-induced germ-cell mutations.

Temporal patterns of DNA adduct formation and glutathione S-transferase activity in the testes of rats fed aflatoxin B1: A comparison with patterns in the liver

“…Other researchers have shown that conjugation of AFB 1 -epoxide with glutathione by GST protects against genetic damage. In rats, chemically induced depression of testicular glutathione caused a significant increase in dominant lethal mutations by ethyl methanesulfonate [Teaf et al, 1987] and enhanced binding of this mutagen to sperm heads [Gandy et al, 1990]. Also, GST is thought to play a major role against testicular toxicity by ethylene oxide in the rat [Mori et al, 1989].…”

“…Several authors have shown that glutathione and GST play an important role in protecting the testis against DNA damage by various genotoxic agents [Teaf et al, 1987;Mori et al, 1989;Gandy et al, 1990]. This mechanism may also play an important role in protecting the testis against DNA damage by AFB 1 .…”

3,5,5‐Trimethyl‐2‐cyclohexen‐1‐on (Isophoron) [MAK Value Documentation in German language, 1995]

“…Darüber hinaus treten wahrscheinlich Konjugate mit Glutathion auf: Isophoron (500 mg/kg KG, einmalig, i.p.) führte bei Sprague-Dawley-Ratten zu signifikanter Abnahme des Glutathiongehaltes in Leber (40%; maximale Reduktion 4 Stunden nach Applikation), Hoden (82%; maximale Reduktion 4 Stunden nach Applikation) und Nebenhoden (72%; maximale Reduktion 8 Stunden nach Applikation) (Gandy 1988;Gandy et al 1990). Um zu klären, ob Isophoron oder seine Metaboliten mit E2V-Globulin assoziiert sind, wurden männliche Ratten (k. w.…”

“…2 Stunden, 1 und 15 Tage nach Behandlung war die 3 H-Ethylmethansulfonat-Bindung gegenüber den Kontrollen unverändert. Ethylmethansulfonat induziert DominantLetal-Mutationen, wobei ein Zusammenhang mit der GSH-Depletion diskutiert wird (Gandy 1988;Gandy et al 1990). Durch die Glutathiondepletion kann es möglicherweise zu einer erhöhten Bindungsrate alkylierender Substanzen kommen.…”

Naphthalin [MAK Value Documentation in German language, 1995]

“…Gabe von 500 mg Naphthalin/kg KG an männliche Sprague-Dawley-Ratten wurde eine mehrstündige Abnahme des Glutathiongehalts in Leber � Nebenhoden � Hoden gefunden (Gandy et al 1990). Eine Naphthalinexposition über das Trinkwasser führte bei Mäusen, Ratten und Meerschweinchen zu einer verminderten Spermatogenese und einer verzögerten Entwicklung der Nachkommen (k.w.A.…”