Benito Soto-Blanco

Does prolonged oral exposure to cyanide promote hepatotoxicity and nephrotoxicity

Long-term exposure to cyanide and/or its main metabolite, thiocyanate, has been associated with goiter, pancreatic diabetes and several neurological disorders. However, very little is found in the literature relating the nephrotoxic and hepatotoxic effects of these substances. Thus, the objective of the present study was to verify the effects of prolonged exposure to potassium cyanide (KCN) in these organs. Forty-six male adults rats, weighing approximately 200 g at the beginning of the experiment, were distributed into five groups-four experimental and one control. Experimental groups were dosed with target doses of 0.3, 0.9, 3.0 or 9.0 mg KCN/kg per day, in the drinking water, during 15 days and the control groups received only tap water. At the end of this experiment, all rats were subjected to euthanasia and plasma samples were obtained in order to determine thiocyanate and thyroidal hormones levels and fragments of thyroid, kidney and liver were collected. Rats treated with the highest cyanide dose (9.0 mg KCN/kg per day) showed lower body weight gain. An increase in the thiocyanate levels was verified in all experimental groups. The histopathologic study revealed hydropic degeneration of the renal tubular epithelial cells in those animals, which received KCN at the dose of 3.0-9.0 mg/kg per day. This study also showed hydropic degeneration of the hepatocytes of those animals, which received KCN at a dose of 9.0 mg/kg per day, and in the thyroid gland an increase was observed in the number of reabsorption vacuoles on follicular colloid, in a dose-dependent manner, in all animals of the experimental groups.

Toxicokinetics of cyanide in rats, pigs and goats after oral dosing with potassium cyanide

The aim of the present study was to determine the effect of the species on the toxicokinetics of cyanide and its main metabolite, thiocyanate. Forty-two rats, six pigs and six goats were dosed orally with 3.0xa0mg KCN/kg body weight, and cyanide and thiocyanate concentrations in blood were measured within 24xa0h. After the single oral dose, KCN was rapidly absorbed by rats and goats, with a time of peak concentration (Tmax) of 15xa0min. The maximum plasma concentration (Cmax) of cyanide was observed in goats (93.5xa0µmol/l), whereas the Cmax of thiocyanate was higher in rats (58.1xa0µmol/l). The elimination half-life (t1/2) and volume of distribution (Vdarea) of both cyanide and thiocyanate were higher in goats (1.28 and 13.9xa0h, and 0.41 and 1.76xa0l/kg, respectively). Whereas the area under the curve (AUC) of cyanide was significantly higher in goats (234.6xa0µmol.l/h), the AUC of thiocyanate was higher in rats (846.5xa0µmol.l/h). In conclusion, the results of the present study support the hypothesis that the metabolism of cyanide and its main metabolite, thiocyanate, is species-linked, with the goat being more sensitive to the toxic effects of cyanide/thiocyanate.

Physiopathological effects of the administration of chronic cyanide to growing goats--a model for ingestion of cyanogenic plants.

Ingestion of cyanogenic plants, such as cassava and sorghum, has been associated with goitre and tropical pancreatic diabetes in both humans and animals. Thus, the objective of the present study was to determine the toxic effects on the thyroid and pancreas in growing goats of prolonged exposure to potassium cyanide (KCN). Thirty-four male goats were divided into five groups dosed with KCN at 0 (control), 0.3, 0.6, 1.2 or 3.0 mg/kg daily for 5 months. Blood samples were obtained in order to determine the glucose, cholesterol, thyroxine (T4), triiodothyronine (T3) and thiocyanate concentrations and for haematological studies; pancreas and thyroid gland were collected for histopathological study. The group receiving the highest dose of cyanide showed lower body weight gains and carcase weights and a decrease in plasma T3 concentrations compared to the control group. Reabsorption vacuoles in follicular colloid and normocytic normochromic anaemia were observed in the experimental animals. Inhibition of peripheral conversion of T4 to T3 is suggested. However, no diabetogenic effects were observed.

Neuropathologic study of long term cyanide administration to goats

Cyanogenic glycosides, which release cyanide, are present in several plant species of high importance for animal production, such as cassava and sorghum. Several human neurological diseases have been associated with chronic cyanide exposure. On the other hand, these effects in ruminants are almost unknown. Thus, the objective of the present study was to determine the long-term lesions of the central nervous system (CNS) caused by daily administration of potassium cyanide (KCN) to goats. Thirty-four male goats were divided into five groups, respectively treated orally with 0 (control), 0.3, 0.6, 1.2 or 3.0 mg KCN/kg/day for 5 months. At the end of the experiment, the whole CNS of each animal was collected for histopathology and immunohistochemistry for apoptotic markers (BAX, BCl2 and CPP32) and for glial fibrillary acid protein (GFAP; vimentin). The results showed the presence of spheroids in the pons, medulla oblongata, and ventral horn of the spinal cord, gliosis and spongiosis in medulla oblongata, gliosis in the pons, and damaged Purkinje cells in the cerebellum from goats that received the higher cyanide dose. In goats from the 1.2 mg KCN/kg group we observed congestion and hemorrhage in the cerebellum, and spheroids in the spinal cord. Gliosis was confirmed by GFAP protein expression. Immunohistochemistry for apoptotic markers and typical apoptotic morphology suggested apoptosis did not participate in the pathogenesis of the observed lesions. Thus, chronic cyanide exposure can promote neuropathological lesions also in goats, and this species can be a useful ruminant model to study the neurotoxic effects of long-term cyanide exposure.

Effects of Long-term Cyanide Ingestion by Pigs

Animal performance and health status are adversely affected by long-term cyanide ingestion; however, the effects of cyanide ingestion by pigs have not been fully determined. The aim of the present study was to determine the effects of prolonged exposure to different doses of potassium cyanide (KCN) in growing-finishing swine. Twenty-four pigs, 45 days of age, were divided into four equal groups and treated with different doses of KCN: 0, 2.0, 4.0 or 6.0 mg per kg body weight per day for 70 consecutive days. The results showed a significant alteration in thiocyanate, creatinine and urea levels and in alanine aminotransferase activity of swine dosed with 4.0 and 6.0 mg/kg/KCN. Thyroid weight was significantly increased in those pigs from 4.0 mg/kg KCN group, but no change in cholesterol, triiodothyronine or thyroline levels were observed. Body and carcase weights, body weight gain, and bacon thickness were not affected by KCN treatment. The histopathological study revealed increased numbers of vacuoles in the colloid of thyroid follicles, degeneration of cerebellar white matter and Purkinje cells, degeneration of renal tubular epithelial cells, caryolysis and pyknosis in hepatocytes, and disturbance of the normal lobular architecture of the liver in all treated pigs. Thus, long-term administration of KCN to swine affects several tissues and could adversely affect animal production.

Lack of protective action of cysteine against the fetotoxic effect of monocrotaline

Monocrotaline (MCT), a pyrrolizidine alkaloid present in Crotalaria species, has hepatotoxic, nephrotoxic, pneumotoxic and fetotoxic effects. However, the toxic effects of exposure to MCT in adult rats can be prevented by cysteine. Thus, the present study was conducted to evaluate the possible prevention by cysteine of the toxic effects of MCT on pregnant rats. Thirty-six pregnant rats were used. The females in the experimental groups were fed ration containing 0.02% MCT, 0.02% MCT + 1% cysteine, or 1% cysteine from day 6 to day 21 of pregnancy; the control group was fed only common ration for the same period of time. All rats were killed on day 21 of pregnancy and their blood was collected for determination of liver and kidney function. General toxicity to pregnant dams was assessed. Fetuses were removed by caesarian section and embryofetotoxic parameters were examined. Results showed impaired body weight gain in rats fed MCT, with or without cysteine supplementation. Plasma levels of AST, ALT, LDH, GGT, urea and creatinine were increased in MCT animals compared to controls. The pathology study revealed lesions only in dams from the MCT group. The weights of the placentas and fetuses of the MCT and MCT + cysteine groups were significantly lower than those of the control group. Thus, the present data suggests some protective action of 1% of cysteine in ration against the toxic effects of MCT on the dams but not on the litter.