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: 2011 vol. 88 p. 307 - 317

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 PGF1, PGE2, PGF2 and TXB2 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 6 hours after LPS administration were significantly attenuated in F overload rats respect to control animals. Oxidative stress parameters were equally affected in the presence or abscence 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 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.