title: Lipopolysaccharide (LPS) induction of nitric oxide synthase-2 and cyclooxygenase-2 is impaired in fructose overloaded rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Carranza
authors.forename: M C
authors.initials: MC
authors.lastname: Litterio
authors.forename: P D
authors.initials: PD
authors.lastname: Prince
authors.forename: M A
authors.initials: MA
authors.lastname: Mayer
authors.forename: P I
authors.initials: PI
authors.lastname: Ingaramo
authors.forename: M T
authors.initials: MT
authors.lastname: Ronco
authors.forename: H A
authors.initials: HA
authors.lastname: Peredo
authors.forename: A M
authors.initials: AM
authors.lastname: Puyó
authors.forename: M
authors.initials: M
authors.lastname: Galleano
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005632:Fructose / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D011453:Prostaglandins; D014280:Triglycerides; D005632:Fructose; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat