Protective Action of Oestrogen against the Lethal Effect of Endotoxin in the Rat

Abstract

DURING investigations on the vascular effects of endotoxin in the isolated rat liver¹, it was noted that the vasoconstrictive response to the administration of bacterial lipopolysaccharide failed to occur if pooled female rather than male rat blood was used as the perfusate, and this prompted an investigation of the value of an oestrogenic compound in prolonging the survival time of rats after the administration of endotoxin. Female albino rats weighing 200–250 g, and male Sprague–Dawley rats weighing 350–400 g, were used. The animals were paired by sex and weight, and each pair was allotted to the treated or control group. Food and water were given freely until the start of the experiment, when they were removed. Conjugated equine oestrogens, expressed as sodium oestrone sulphate, were given intraperitoneally and each rat received 4 mg dissolved in 1 ml. of diluent at various intervals before and after the intraperitoneal administration of purified lipopolysaccharide (E. coli 0127 : B8, Difco Laboratories, Detroit). The diluent was given at the same intervals to the control animals. The numbers of survivors in the treated and untreated groups were recorded at 18 and 24 h. The few deaths occurring after 24 h were not included in the results, and statistical significance was determined by the method of χ² using Yates correction.