Salicylate prevents hepatic oxidative stress activation caused by short-term elevation of free fatty acids in vivo.
It has been reported that high-dose salicylates, an IKKss inhibitor, may prevent FFAs-induced insulin resistance. In previous study, we found that in FFAs-induced insulin resistant rats, administration of salicylate was associated with a reduction of plasma malondialdehyde (MDA). In the present study, we investigated the effects of sodium salicylate on FFAs-induced insulin resistance and on oxidative stress in liver. Overnight-fasted Wistar rats were subject to 7h i.v. infusion of either saline or Intralipid plus 20U/ml heparin (IH) with or without salicylate. Hyperinsulinemic-euglycemic clamp with tracer infusion was performed to assess insulin-induced suppression of endogenous glucose production (EGP). Oxidative antioxidant markers, immunohistochemical inducible nitric oxide synthase (iNOS) stain, nitric oxide (NO), MDA, Superoxide dismutase (SOD) activity in liver was measured. Infusion of IH markedly decreased insulin-induced suppression of EGP, which were completely prevented by salicylate co-infusion. Furthermore, salicylate reversed IH-induced (1) increase in iNOS and NO expression in the liver; (2) increase in MDA/SOD in the liver. This study provides preliminary assessments of efficacy of sodium salicylate as a new treatment for FFAs-induced insulin resistances. The effect of increasing insulin sensitivity by salicylate in part may be secondary to reduce the oxidative stress in liver.
He
Bing
B
Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Zhao
Sheng
S
Zhang
Wei
W
Li
Yan
Y
Lu
Yan
Y
Han
Ping
P
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D012980:Sodium Salicylate