Chronic N-acetylcysteine prevents fructose-induced insulin resistance and hypertension in rats.
We examined if administration of an antioxidant compound protects against the development of insulin resistance and hypertension. Male rats were assigned randomly into four groups, and treated for 12 weeks with normal chow, normal chow plus N-acetylcysteine (1.5 g/day/kg), fructose (60% of diet), and fructose plus N-acetylcysteine. After 10 weeks, plasma triglyceride and 15-F2t-isoprostane, and insulin sensitivity were measured, and after 12 weeks, pressor response to methoxamine (15-60 microg/kg min) was assessed. Relative to normal chow-fed controls, the fructose-fed rats had increased blood pressure, plasma insulin, triglyceride and 15-F2t-isoprostane, and decreased insulin sensitivity; these changes were inhibited by N-acetylcysteine. Maximal pressor response to methoxamine was attenuated in the fructose-fed rats given N-acetylcysteine relative to the other three groups. Therefore, chronic treatment with N-acetylcysteine increases insulin sensitivity and prevents the blood pressure increase associated with fructose feeding in rats, the mechanism may involve the decrease of oxidative stress and alpha-adrenoceptor-mediated vasoconstriction.
Song
Dongzhe
D
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Heath Science Mall, Vancouver, BC, Canada V6T 1Z3.
Hutchings
Simon
S
Pang
Catherine C Y
CC
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000517:prevention & control*; D007333:Insulin Resistance; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D000316:Adrenergic alpha-Agonists; D014280:Triglycerides; C075750:8-epi-prostaglandin F2alpha; D005632:Fructose; D015237:Dinoprost; D008729:Methoxamine; D000111:Acetylcysteine