Toxicity of palytoxin

The toxicity of palytoxin in sue unanesthetized animal species was established as well as the toxicity of the toxin when administered by various routes. Tables I and II show the doses and numbers of animals used in this phase of the study. 

Table I. Intravenous Toxicity of Palytoxin in Several Animal Species...

Table IH. Toxicity of Palytoxin in Rats When an Initial Sublethal Dose is Followed by a Lethal Dose...

Table VI. Toxicity of Palytoxin in Monkeys (Normal) When an Initial Sublethal ...

The iv toxicity of palytoxin is shown in Table I. Rabbits and dogs appear to be the sensitive to palytoxin rats and guinea pigs appear less sensitive. Table II shows the comparative toxicity of palytoxin administered by several routes - again iv palytoxin is extremely toxic while ir and po are relatively without toxic effects. 

Ito K., Urakawa, N., and Koike, H. 1982. Cardiovascular toxicity of palytoxin in anesthetized dogs. Arch Int Pharmacodyn Ther 25 ., 146-154. 

Toxicity of Palytoxins to Cultured Cells and to Isolated Tissue In Vitro. 696... 

TOXICITY OF PALYTOXINS TO CULTURED CELLS AND TO ISOLATED TISSUE IN VITRO... 

TABLE 32.4 Acute Toxicity of Palytoxin and Extracts of Palytoxin-Containing Organisms by Intravenous Injection ... 

Comparatively little information on the oral toxicity of palytoxins is available (Table 32.6), but it is clear that these substances are very much less toxic orally than by intravenous or intraperitoneal injection. In an early study, Vick and Wiles [90] reported an oral LD50 of >40 [tg/kg in rats. In later work, the LD50 of purified palytoxin from P. caribaeorum was established as 510 [tg/kg in mice... 

The toxicity of palytoxin via several other routes of administration has been investigated (Table 32.7). This substance is highly toxic after intramuscular or subcutaneous injection, or following intratracheal instillation [90,96]. No toxicity was recorded after intrarectal administration of palytoxin at 10 [tg/kg [90]. Renal necrosis and pulmonary damage were recorded in animals given palytoxin intradermally [96], and local irritation and swelling, associated with edema and necrosis, were observed after both intradermal injection and percutaneous application. Severe irritation, involving ulceration and conjunctivitis, was induced by application of palytoxin to the eye [96]. 

Very little information on the chronic toxicity of palytoxin is available. Ito et al. [103] gave 5, 10, 15, or 29 intraperitoneal injections of 0.25 [tg/kg palytoxin (pnrified from D. alcalai) to mice, five times per week. Diarrhea and peritonitis were recorded in 60% of mice given 29 doses of the test snbstance, while decreased thymic weights and increased splenic weights were observed after... 

Palytoxin derivatives are exceptionally toxic to cells and tissue in vitro, with effects being recorded at nanomolar concentrations. Such in vitro studies have proved very important in identifying the effect of palytoxin on ion movements across the cell membrane involving the Na,K-ATPase, and palytoxin has proved valuable in investigating the mechanism of action of ion pnmps [ 110,111 ]. In many cases, it was shown that the toxicity of palytoxin to cells was cansed by osmotic lysis dne to interaction with the Na,K-ATPase, as shown by the ability of onabain to prevent cytotoxicity, bnt whether snch effects are relevant to the toxicity of palytoxin in vivo is donbtfnl. Effects on ion transport have never been demonstrated in vivo, and ouabain had no effect on palytoxin toxicity in vivo [93]. 

The acute toxicity of palytoxin by injection has been very well evaluated, with good data available on the lethal doses of this substance to many species of animals by various routes of injection. There is no doubt that injected palytoxin, whether administered via the intraperitoneal, intravenous, intramuscular, or subcutaneous route, is an exceptionally toxic compound. There is, however, surprisingly little information available on the oral toxicity of palytoxin. The major focus of toxicological studies on food contaminants such as palytoxin shonld be risk assessment, and since such contaminants are eaten, not injected, in assessing risks to hnman health of food, oral data are of paramount importance. What data there are indicate that palytoxin is very much less toxic when given orally than when administered by injection. In a comparative stndy, more than 700 times more palytoxin was required to kill mice via gavage than by intraperitoneal injection. Similarly, a crude extract of... 

The toxicity of palytoxin, determined by experiments and molecular modeling, originates in its disabling of the sodium/potassium cell membrane pump (see chapter 8). 

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