N-acetylcysteine prevents MAA induced male germ cell apoptosis: role of glutathione and cytochrome c.
Exposure to methoxyacetic acid (MAA), a major byproduct of the paint industry, causes testicular atrophy in multiple species. This study demonstrates DNA breakdown in rat germ cells after exposure to MAA in vivo within 12 h, leading to 40% germ cell death by 24 h. Within 4 h of treatment, cytochrome c is released from the mitochondria into the cytosol without the involvement of mitochondrial potential loss, reactive oxygen species generation or lipid peroxidation events. Peak activation of caspase-9 and caspase-3 is detectable post treatment at 4 and 8 h respectively. There is a decrease in germ cell glutathione levels within 2 h of MAA treatment. Replenishment of glutathione by pretreatment of the animals with the antioxidant N-acetylcysteine prior to MAA treatment could prevent the release of cytochrome c, DNA fragmentation and cell death.
Rao
A V S Kondala
AV
National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India.
Shaha
Chandrima
C
D000085:Acetates / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000085:Acetates; D000975:Antioxidants; D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C013598:methoxyacetic acid; D005978:Glutathione; D000111:Acetylcysteine