Inhibitory effect of dimethyl sulfoxide (DMSO) on necrosis and oxidative stress caused by D-galactosamine in the rat liver.
D-Galactosamine (D-Galn: 300 mg/kg) was intraperitoneally administered to rats. After 6 h the activity of plasma GOT and GPT was significantly higher than that of the control group and plasma GOT and GPT activities increased thereafter. These results indicated that the necrotic process was initiated at about 6 h and developed thereafter. With coadministration of DMSO (1 h before administration of D-Galn: 2.5 mL/kg, oral), plasma GOT and GPT were significantly lower, showing that DMSO inhibited the necrotic action of D-Galn. After 6-24 h of D-Galn administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after D-Galn intoxication and thereafter. DMSO significantly restored the liver vitamin C level 24 h after D-Galn injection, demonstrating that DMSO effectively ameliorated the oxidative stress caused by D-Galn, resulting in the prevention of necrosis of the liver. Phosphorylated JNK and phospho-ERK were significantly increased transiently 6-12 h after treatment with D-Galn. These results indicated that oxidative stress and the activation of JNK took place almost simultaneously. Phosphorylated p38 MAPK was not changed and DMSO treatment did not affect the change of these MAPKs by D-Galn.
Iida
Chinatsu
C
Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
Fujii
Kozue
K
Koga
Eriko
E
Washino
Yukiko
Y
Ichi
Ikuyo
I
Kojo
Shosuke
S
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016166:Free Radical Scavengers; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide