Protective effect of chlorpromazine against the lethality of interleukin 1 in adrenalectomized or actinomycin D-sensitized mice

Interleukin 1 (IL-1) and Tumor Necrosis Factor (TNF) are thought to play a key role in septic shock and inflammation. We have tested the effect of dexamethasone (DEX) and chlorpromazine (CPZ) on the lethal effect of IL-1, TNF and endotoxin. Two different experimental models were used to sensitize mice to the lethal effect of IL-1: adrenalectomy and pretreatment with actinomycin D. CPZ (4 mg/kg) was found to protect mice against IL-1 and endotoxin toxicity in all cases, while DEX had a protective effect only in adrenalectomized mice. In contrast to its protective effect against IL-1 and endotoxin, CPZ did not protect mice against TNF. These findings might be useful in the analysis of the differences in the actions of IL-1 and TNF in vivo, and in the development of new drugs preventing their toxicity.     

Protective effect of C-reactive protein against the lethality induced by Vibrio vulnificus lipopolysaccharide

Vibrio vulnificus infection has attracted special interest because of its high mortality. A strong clinical association exists between hepatic dysfunction and increased morbidity and mortality from V. vulnificus infection. In this study, the effect of C-reactive protein (CRP), a typical hepatogenic acute phase protein, on the lethality induced by V. vulnificus lipopolysaccharide (LPS) was investigated in galactosamine-sensitized mice. The pretreatment of CRP, in a dose of at least 2 mg/kg, 2 hr before the challenge of LPS completely protected mice against the lethality by V. vulnificus LPS. The elevation of serum tumor necrosis factor-alpha (TNF-alpha) induced by LPS administration was not affected by CRP pretreatment. However, the LPS- or TNF-alpha-induced hepatotoxicity was completely prevented by CRP. These results indicate that CRP does not prevent the synthesis, but prevents the hepatotoxic action of TNF-alpha. The possibility that impaired production of acute phase proteins in patients with pre-existing hepatic dysfunction may predispose the higher risk of V. vulnificus infection needs to be evaluated further.     

Protective effect of zinc against spontaneous malformations and lethality inBufo arenarum embryos

In a retrospective study, it was found that zinc (1 mg Zn²⁺/L) had a protective effect in anomalous batches ofBufo arenarum embryos characterized by a high incidence of spontaneous mortality and morphological alterations.