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

AimsFructose (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 methodsNO blood steady-state concentration was monitored through the detection of nitrosyl–hemoglobin complexes (NO–Hb) by electronic spin resonance. Production of 6-keto PGF1α, PGE2, PGF2α 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 findingsOur results showed that increases in NO circulating steady-state concentration and PR production by aorta and mesenteric beds 6 h 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).SignificanceThese 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.