Lipopolysaccharide (LPS) induction of nitric oxide synthase-2 and cyclooxygenase-2 is impaired in fructose overloaded rats.

A CARRANZA; M.C. LITTERIO; P.D. PRINCE; M.A. MAYER; P.I. INGARAMO; M.T. RONCO; H.A. PEREDO; A.M. PUYÓ; M. GALLEANO

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2010 vol. 88 p. 307 - 313

0024-3205

AIMS: Fructose (F) overload in rats induces metabolic dysfunctions that resemble the human metabolic syndrome. In this paper, we aimed to investigate the response of F overload rats to lipopolysaccharide (LPS) challenge in terms of nitric oxide (NO) production and prostanoids (PR) release. MAIN METHODS: NO blood steady-state concentration was monitored through the detection of nitrosyl-hemoglobin complexes (NO-Hb) by electronic spin resonance. Production of 6-keto PGF(1)α, PGE(2), PGF(2)α and TXB(2) was measured in aorta and mesenteric beds by HPLC. Western blot analysis was used to examine the changes in the expression levels of NOS-2 and COX-2 in aorta. KEY FINDINGS: Our results showed that increases in NO circulating steady-state concentration and PR production by aorta and mesenteric beds 6h after LPS administration were significantly attenuated in F overload rats with respect to control animals. Oxidative stress parameters were equally affected in the presence or absence of the F treatment. Aorta protein levels of NOS-2 and COX-2, two enzymes inducible by LPS, were significantly lower in F overload rats with respect to control rats at the end of the treatment (-39% and -61% for NOS-2 and COX-2 respectively). SIGNIFICANCE: These results suggest that the metabolic alterations established by 15 weeks of F overload should affect the response to LPS challenge due to an attenuation in the induction of NOS-2 and COX-2. This effect would be one of the components contributing to abnormalities in the course of the inflammatory response in other conditions associated to insulin resistance, such as diabetes.