3.1.5. Toxicity Studies

So far, there are no records of human poisoning by *T. esculenta*, probably because seeds and leaves are not consumed in the fresh form, only the pulp; however, there are records of intoxication in some animals, such as sheep and cattle that ingest leaves and seeds without heat treatment, which may indicate that the toxic compound is affected by high temperatures [68].

The Northeastern region of Brazil presented an outbreak of spontaneous poisoning in sheep and cattle, which showed severe signs of nervous system damage, some irreversible. Thus, an experimental reproduction of the poisoning was carried out with 5 sheep by administering 30–60 g of leaves per kilogram of body weight, and two sheep with doses of 5–10 g of seeds per kilogram of body weight, with samples from different regions of Brazil. All sheep showed clinical signs of intoxication 72 h after exposure. The main signs and symptoms were mild to moderate tympanism, drowsiness, ataxia, depressive behavior and humeral hypomotility. The chemical compound present in leaves and seeds responsible for the toxic effect is still unknown. In addition, the minimum amount that exerted toxicity was lower for seeds than for leaves, indicating greater potential for seed toxicity [69].

In the same region, cattle spontaneously intoxicated with the same clinical signs, were analyzed 72 h after exposure. In autopsy exams, partially digested seeds and leaves were found in the rumen. Laboratory and histological exams showed no significant changes, either in spontaneous or experimental poisoning. However, the presence of seeds in the rumen content associated with clinical signs suggests that there is risk of human poisoning by both seeds and leaves [70]. Similar clinical signs were observed in a dog after ingestion of *T. esculenta* seeds. Although the substance responsible for the toxicity is unknown, the induction of inflammatory response by lectin found in seeds is the

focus of a study that describes the recruitment of neutrophils and mononuclear cells caused by lectin. The proposed mechanism is related to the specific properties of lectin binding to carbohydrates in the cell membrane [71,72].

In contrast, Wistar rats treated with purified aqueous extract from *T. esculenta* leaves and stem at oral doses of 5, 50, 300 and 2000 mg did not show any sign of acute toxicity, and regardless of dose, there were no abnormal signs in comparison with control animals. Water intake and body weight did not change during the experimental period and the biochemical and hematological parameters showed no abnormalities. After euthanasia, heart, lung, spleen, kidney and liver samples were collected for pathological evaluation and also showed no signs of abnormality, which may be related to the lectin concentration, which is higher in seeds than in leaves and stem; therefore, the absence of toxicity may be due to the fact that seeds were not used in this study [35].
