N-Acetyl-L-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization.
Intense exercise leads to post-exercise lymphocytopenia and immunosuppression, possibly by triggering lymphocyte apoptosis. To test the role of oxidative stress on exercise-induced lymphocyte apoptosis, we administered the antioxidant N-acetyl--cysteine (NAC) and measured apoptosis in intestinal lymphocytes (IL) from exhaustively exercised animals. Eighty-seven female C57BL/6 mice were randomly assigned to receive NAC (1 g/kg) or saline 30 min prior to treadmill exercise for 90 min at 2degrees slope (30 min at 22 m min(-1), 30 min at 25 m min(-1), and 30 min at 28 m min(-1)) and sacrificed immediately (Imm) or 24 hours (24 h) after cessation of exercise. Control mice (nonexercised) were exposed to treadmill noise and vibration without running. Exercise increased IL phosphatidylserine externalization (p<0.001), mitochondrial membrane depolarization (p<0.05), and decreased intracellular glutathione concentrations (p<0.05) immediately following exercise in saline relative to nonexercised mice. At 24 h post-exercise, saline injected mice had fewer total (p<0.001) and CD3+ (p<0.005) IL compared to nonexercised animals. NAC injection in mice maintained intracellular glutathione levels, prevented phosphatidylserine externalization, mitochondrial membrane depolarization, and loss of IL immediately and 24 h after exercise. These data suggest that lymphocyte apoptosis precedes post-exercise lymphocytopenia and may be due to oxidative stress.
Quadrilatero
J
J
Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, Ont., Canada.
Hoffman-Goetz
L
L
D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D017252:CD3 Complex / Q000378:metabolism; D002470:Cell Survival; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008214:Lymphocytes / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D012420:Running
D000975:Antioxidants; D017252:CD3 Complex; D016877:Oxidants; D006861:Hydrogen Peroxide; D005978:Glutathione; D000111:Acetylcysteine