Effect of canatoxin on the circulating levels of gonadotropins and prolactin in rats.

1. The effects of canatoxin, the toxic principle from Canavalia ensiformis seeds which has lipoxygenase-activating properties, were evaluated in rats using radioimmunoassay techniques to measure plasma levels of prolactin (PRL), progesterone, follicle stimulating (FSH) and luteinizing (LH) hormones. 2. The chronic administration of canatoxin (50, 100 or 200 micrograms/kg daily for 12 days, ip) to female rats induced a sharp rise in plasma LH and FSH concentrations with no changes in progesterone level. A fall in circulating PRL was also observed. The frequency of proestrus and weight gain increased in rats treated with the highest dose of toxin used, but there was no alteration in weight of uterus or ovaries. 3. The increases in gonadotropin levels with canatoxin are consistent with the lipoxygenase-activating properties of the toxin, but do not explain why plasma PRL concentrations decreased in canatoxin-treated rats. 4. Since the animals in the control group had high PRL and low LH levels and since canatoxin increased LH and decreased PRL in the circulation, a possible stress-prevention effect is discussed for the toxin. 5. This study supports previous suggestions of central actions for canatoxin, and indicates the hypophysis and/or hypothalamus as one of the target sites for the toxin in the central nervous system.

Convulsions induced by canatoxin in rats are probably a consequence of hypoxia.

Canatoxin, a convulsant neurotoxin from the seeds of Canavalia ensiformis, induces lipoxygenase-dependent hypoxia and sex-related alterations of carbohydrate metabolism in rats which are blocked by glucose, diazepam and hexamethonium. The present study analyzes the possible casual relationship between the convulsant action of canatoxin and its effects on carbohydrate metabolism. The incidence of canatoxin-induced convulsions was greater in male than in female rats. Pretreatment of male rats with drugs that block hypoxia, such as glucose (2.5 g/kg, iv, 15 min), diazepam (5 mg/kg, ip, at 48 h, 24 h and 15 min), hexamethonium (4 mg/kg, ip, 15 min) and NDGA (125 mg/kg, ip, 1 h), also protected the animals against convulsions, respiratory distress and death. These results suggest that canatoxin-induced convulsions are probably the consequence of hypoxia and both effects are mediated by lipoxygenase activation.

Sex-related canatoxin-induced blood glucose alterations in the rat.

1. The present study was designed to characterize sex-related canatoxin-induced blood glucose alterations in rats. 2. Chronic administration of canatoxin (50 mU, ip, daily for 3 days) induced hypoglycemia in female rats (N = 6) (-36.54 +/- 3.24%, P less than 0.05). The response of pregnant rats (N = 8) was similar to that observed for male rats (+29.57 +/- 4.70%). 3. Administration of canatoxin did not modify blood glucose levels of gonadectomized male or female rats. Similarly, pretreatment of intact male or female rats with human chorionic gonadotropin (40 IU/kg, im) blocked the effect of canatoxin on blood glucose levels. 4. Gonadal steroid replacement (testosterone, 10 mg/kg, im) for gonadectomized male rats did not reverse the inhibition of canatoxin-induced blood glucose alterations, whereas pretreatment of intact female rats (N = 6) with testosterone (10 mg/kg, im) significantly attenuated the canatoxin-induced hypoglycemia. 5. These data indicate that the blood glucose alterations produced by canatoxin in rats are under hormonal regulation.

Blood glucose alterations induced in rats by canatoxin, a protein isolated from jack bean (Canavalia ensiformis) seeds.

Canatoxin, a lethal convulsant protein isolated from the seeds of Canatoxin ensiformis (jack bean), induced a biphasic alteration in blood glucose levels when injected i.v. into rats and mice. After administration of subconvulsant doses of canatoxin the rats showed initially hyperglycemia during the first 30 min, followed by a long-lasting hypoglycemia. Return to basal glucose levels was not seen up to 15 days. The hyperglycemic effect was dose-dependent and occurred in starved and well-fed animals. A parallelism between convulsant and hyperglycemic activity was observed throughout all canatoxin purification steps. Mice were about 20-fold less sensitive (on a weight basis) than rats to canatoxin-induced hyperglycemia. The hyperglycemic phase was not affected by pretreatment of the rats with alpha- or beta-adrenergic blockers or chlorpromazine, but was potentiated by reserpine and haloperidol. Diazepam and hexamethonium were able to block the hyperglycemic phase of canatoxin's effect. The results suggest that the hyperglycemic alterations induced by canatoxin in rats and mice are probably mediated via the central nervous system.