Yonsei Med J.  2001 Feb;42(1):114-119. 10.3349/ymj.2001.42.1.114.

Increase in rat plasma antioxidant activity after E. coli lipopolysaccharide administration

• Lee KY
• Perretta S
• Zar H
• Mueller RA
• Boysen PG

• KMID: 720594
• DOI: http://doi.org/10.3349/ymj.2001.42.1.114

Abstract

It is well recognized that the sensitivity of animals to lipopolysaccharide (LPS) endotoxin varies tremendously. And, it has been recently observed that Sprague-Dawley rats dramatically increase the activity of hepatic endogenous antioxidative enzyme systems after LPS administration. This finding suggests that the relative resistance of rats to LPS may be related to a concomitant increase in the activities of the hepatic antioxidant systems. This study was designed to examine if the above reported hepatic change in rats given LPS could be observed at the systemic level. Male Sprague-Dawley or Wistar rats, weighing 250 - 350 g, were given increasing doses (10 - 100 mg/kg) of LPS i.p. under 1.0% isoflurane anesthesia. Antioxidant capacity (AOC), blood gas analysis, and the cardiovascular parameters of the arterial blood of animals were determined over a 4 hour period following LPS administration. In addition, we studied the effect of pretreatment with the non-specific nitric oxide synthase inhibitor, L-N(G)-Nitroarginine methyl ester hydrochloride (L-NAME), given 50 mg/kg s.c. one and 24 hours before the administration of 20 mg/kg LPS i.p. in Sprague-Dawley rats. Rats given sufficiently high doses of E. coli LPS to produce behavioral effects also showed increased plasma AOCs in the early period after the administration of LPS. Similar changes were noted in Sprague-Dawley and Wistar rat strains, but at different doses that reflect their differential sensitivities to the LPS induced inflammatory response. Also, the resistance of the Sprague-Dawley strain of rats to LPS was not altered by the prior administration of L-NAME, nor was the plasma AOC altered. In conclusion, our study suggests that the rat strains are relatively resistant to develop the toxic signs of LPS in the early period after the administration of LPS, especially in Sprague-Dawley rats. Moreover, endotoxin-induced increases in plasma AOC may contribute to the rats' resistance to LPS intoxication.

Keyword

E. coli endotoxin; antioxidant capacity; nitric oxide synthase inhibition; blood pressure; arterial blood gas

MeSH Terms

Animal
Antioxidants/analysis*
Blood Pressure/drug effects
Escherichia coli/pathogenicity*
Lipopolysaccharides/toxicity*
Male
NG-Nitroarginine Methyl Ester/pharmacology
Nitric-Oxide Synthase/physiology
Nitric-Oxide Synthase/antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Rats, Wistar