Long-term treatment with N-acetylcysteine, but not caloric restriction, protects mesenchymal stem cells of aged rats against tumor necrosis factor-induced death.
The survival of mesenchymal stem cells (MSCs) to tumor necrosis factor alpha (TNFalpha) stimulation was evaluated after a long-term antioxidant treatment, or caloric restriction, in aged rats. MSCs were isolated from bone marrow of 30-month-old rats which orally received N-acetylcysteine in the last 18 months. The necrotic cell death-induced in vitro by TNFalpha, determined by trypan blue exclusion, was markedly attenuated in MSCs obtained from treated vs. control aged rats (percent mean+/-SEM: 10.9+/-2.17 vs. 17.8+/-0.53; p<0.05). Also, the proliferation rate of MSCs from control, but not N-acetylcysteine-treated, aged rats evaluated up to 2 weeks was significantly higher than that of MSCs from younger (4-month-old) rats. No significant effect was observed relative to the parameters investigated when the aged rats were previously subjected to a hypocaloric diet for 18 months. In conclusion, a prolonged supplementation with N-acetylcysteine in rats can increase resistance to necrotic death of MSCs and may also counteract an excessive rate of MSC proliferation.
Muscari
Claudio
C
Department of Biochemistry, University of Bologna, Bologna, Italy. claudio.muscari@unibo.it
Bonafe'
Francesca
F
Farruggia
Giovanna
G
Stanic
Ivana
I
Gamberini
Chiara
C
Carboni
Marco
M
Basile
Ilaria
I
Giordano
Emanuele
E
Caldarera
Claudio Marcello
CM
Guarnieri
Carlo
C
D000111:Acetylcysteine / Q000494:pharmacology*; D000375:Aging / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D031204:Caloric Restriction; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004334:Drug Administration Schedule; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine