Biochemical and pathological effects of Clostridium difficile toxins in mice.

Toxins produced by Clostridium difficile are lethal to mice after i.p. administration. Among the alterations observed when mice were given a preparation containing both Toxin A and Toxin B were a 1.6 +/- 0.2 degrees C (mean +/- S.E., N = 7) depression of rectal body temperature, blood in the liver (318 +/- 13% of control levels) and a decrease in glutathione concentration (74 +/- 2% of control). Purified Toxin A and purified Toxin B were both able to alter these parameters. Toxin B, however, had a more profound effect on serum isocitrate dehydrogenase levels (raised to 198 +/- 18% of control) and liver O-demethylase activity (reduced to 64 +/- 8% of control), parameters sensitive to alteration in liver damage. The effects of Toxin B on these parameters were partially alleviated in mice pretreated with N-acetylcysteine (1.2 g/kg i.p.) and triamcinolone (120 mg/kg i.p.) and, although the percentage of survivors did not improve, survival time was increased from 3.0 +/- 0.1 hr to 4.6 +/- 0.5 and 5.7 +/- 1.3 hr, respectively, by these agents.