Histamine toxicity

Bjeldanes, L., Shultz, D.E. and Morris, M.M. (1978). On the aetiology of scombroid poisoning cadaverine potentiation of histamine toxicity in the guinea-pig, Food Cosmet. Toxicol., 16, 157. 

This paradox between the lack of toxicity of pure histamine and the apparent toxicity of equivalent doses of histamine in spoiled fish could be explained by the existence of potentiators of histamine toxicity in spoiled fish. These potentiators would serve to lower the threshold dose of histamine necessary to elicit scombroid poisoning symptoms in humans. 

Several possible potentiators of histamine toxicity have been suggested by various in vivo and in vitro experiments, although none of these substances has been clearly implicated in scombroid poisoning. 

Further experiments will be necessary with fish incriminated in histamine poisoning outbreaks to confirm the presence and identity of any potentiators of histamine toxicity. 

The hypothesis that histamine toxicity could be potentiated by inhibition of histamine-metabolizing enzymes was supported by early experiments that demonstrated a potentiation of histamine- induced contractions of smooth muscle by inhibitors of DAO (22.23). 

Further research will be necessary to demonstrate conclusively that inhibition of histamine metabolism is responsible for the potentiation of histamine toxicity that is apparently observed in scombroid poisoning. In vivo experiments will be necessary to show that hepatic histamine metabolism is also compromised by the ingestion of suspected potentiators. Also, the effectiveness of cadaverine and other possible potentiators must be demonstrated under conditions where the histamine level exceeds the potentiator concentration by a factor of approximately 10. This concentration ratio would parallel that found in spoiled tuna more closely than the levels used in the experiments of Lyons et al. (48). 

Given the vast molar excess of mucin to histamine in the gastrointestinal tract, it is difficult to envision that such inhibition of binding would play more than a secondary role in the potentiation of histamine toxicity. 

In both humans and guinea pigs, histamine causes bronchoconstriction mediated by Hi receptors. In the guinea pig, this effect is the cause of death from histamine toxicity, but in humans with normal airways, bronchoconstriction following small doses of histamine is not marked. 

Since heparin protected the animals from histamine toxicity in a dose-response, it was thought to be safe to use in human patients for clinical trial. Heparin had of course been used in cardiovascular disease in large doses for many years. It was believed that there would be safety as long as the dosage was kept within the half gram used in cardiovascular disease. Further, since heparin was bound by histamine in the animal studies, it was believed that it would not be free in the blood to cause bleeding difficulties. Lee-White tests were performed on many of the patients and confirmed this finding. 

Isomer Prevention of histamine toxicity ED50 (mg/kg sc) Prevention of histamine spasm pA2... 

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