Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues

Kenneth S. Helmer, Yan Cui, Ashvin Dewan, David W. Mercer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Ketamine and xylazine (K/X) are commonly used in combination as an anesthetic agent in experimental animal models. We previously noted that K/X attenuated lipopolysaccharide (LPS)-induced liver injury, gastric stasis, and reduced symptoms of endotoxemia. Because ketamine attenuates expression of several proinflammatory genes, we examined the effects of K/X on inducible nitric oxide synthase (iNOS), which has been implicated in endotoxin-induced tissue injury. We hypothesized that K/X would attenuate LPS-induced expression of iNOS in various organs in the rat. Rats were given either intraperitoneal saline or ketamine (70 mg/kg) and xylazine (6 mg/kg) 1 h before saline or LPS (20 mg/kg). Rats were sacrificed 5 h later and stomach, duodenum, jejunum, ileum, colon, liver, lung, kidney, and spleen were collected for determination of iNOS protein immunoreactivity by Western immunoblot. Data reported in densitometric units (DU) as mean ± SEM (n ≥ 5; ANOVA). LPS significantly increased iNOS protein immunoreactivity in all tissues examined versus saline controls (P ≤ 0.05, all groups). K/X significantly attenuated LPS-induced iNOS protein immunoreactivity in all of the aforementioned organs (P ≤ 0.05, all groups). Furthermore, K/X almost completely blunted LPS-induced expression of iNOS in stomach, duodenum, jejunum, and colon. These data indicate that K/X attenuates LPS-induced upregulation of iNOS in a variety of tissues. Furthermore, in rat models studying the in vivo effects of endotoxin, especially those evaluating the gastrointestinal system, careful consideration needs to be given if the anesthetic combination of K/X is used, as it alters LPS-induced expression of iNOS, an important pathophysiologic mediator in endotoxemia.

Original languageEnglish (US)
Pages (from-to)70-78
Number of pages9
JournalJournal of Surgical Research
Volume112
Issue number1
DOIs
StatePublished - Jun 1 2003

Fingerprint

Xylazine
Ketamine
Nitric Oxide Synthase Type II
Lipopolysaccharides
Endotoxemia
Jejunum
Duodenum
Endotoxins
Anesthetics
Stomach
Colon
Gastroparesis
Proteins
Liver
Wounds and Injuries
Ileum
Analysis of Variance
Up-Regulation
Spleen
Animal Models

Keywords

  • Endotoxemia
  • Inducible nitric oxide synthase
  • Lipopolysaccharide
  • Organ injury

ASJC Scopus subject areas

  • Surgery

Cite this

Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues. / Helmer, Kenneth S.; Cui, Yan; Dewan, Ashvin; Mercer, David W.

In: Journal of Surgical Research, Vol. 112, No. 1, 01.06.2003, p. 70-78.

Research output: Contribution to journalArticle

Helmer, Kenneth S. ; Cui, Yan ; Dewan, Ashvin ; Mercer, David W. / Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues. In: Journal of Surgical Research. 2003 ; Vol. 112, No. 1. pp. 70-78.
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