Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.
We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes.
Sagara
M
M
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Satoh
J
J
Zhu
X P
XP
Takahashi
K
K
Fukuzawa
M
M
Muto
G
G
Muto
Y
Y
Toyota
T
T
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019270:Fructosamine; D006595:Hexosamines / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D006595:Hexosamines; D012709:Serum Albumin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019270:Fructosamine; D000111:Acetylcysteine