The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.
Natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) sometimes occurs in tropical regions of the world. Polyhydroxylated alkaloids were isolated from the leaves, flowers, and seeds of the poisonous plant and characterized. Chromatographic separation of the leaf extract resulted in the isolation of swainsonine (1), 2-epi-lentiginosine (2), calystegines B(1) (3), B(2) (4), B(3) (5), and C(1) (6), and N-methyl-trans-4-hydroxy-l-proline (7). The contents of 1 in the fresh leaves and flowers were 0.0029 and 0.0028%, respectively, whereas the contents of 1, 3, and 4 in the seeds were approximately 10 times higher than those in the leaves and flowers. Alkaloids 3, 4, and 6 showed a potent inhibitory activity toward rat lysosomal beta-glucosidase, with IC(50) values of 2.1, 0.75, and 0.84 microM, respectively, and alkaloid 5 was a moderate inhibitor of alpha- and beta-mannosidases. Although alkaloid 1 is known as a powerful inhibitor of lysosomal alpha-mannosidase (IC(50) = 0.02 microM), alkaloid 2, which has been thought to be an intermediate in the biosynthesis of 1, was also a potent inhibitor of alpha-mannosidase with an IC(50) value of 4.6 microM.
The aim of this trial was to implement a method to obtain a tool for analyses of tramadol and the main metabolite, o-desmethyltramadol (M1), in goat's plasma, and to evaluate the pharmacokinetics of these substances following intravenous (i.v.) and oral (p.o.) administration in female goats. The pharmacokinetics of tramadol and M1 were examined following i.v. or p.o. tramadol administration to six female goats (2 mg/kg). Average retention time was 5.13 min for tramadol and 2.42 min for M1. The calculated parameters for half-life, volume of distribution and total body clearance were 0.94+/-0.34 h, 2.48+/-0.58 L/kg and 2.18+/-0.23 L/kg/h following 2 mg/kg tramadol HCl administered intravenously. The systemic availability was 36.9+/-9.1% and half-life 2.67+/-0.54 h following tramadol 2 mg/kg p.o. M1 had a half-life of 2.89+/-0.43 h following i.v. administration of tramadol. Following p.o., M1 was not detectable.
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 3.0 mg KCN/kg body weight, and cyanide and thiocyanate concentrations in blood were measured within 24 h. After the single oral dose, KCN was rapidly absorbed by rats and goats, with a time of peak concentration ( T(max)) of 15 min. The maximum plasma concentration ( C(max)) of cyanide was observed in goats (93.5 micro mol/l), whereas the C(max) of thiocyanate was higher in rats (58.1 micro mol/l). The elimination half-life ( t(1/2)) and volume of distribution ( Vd(area)) of both cyanide and thiocyanate were higher in goats (1.28 and 13.9 h, and 0.41 and 1.76 l/kg, respectively). Whereas the area under the curve (AUC) of cyanide was significantly higher in goats (234.6 micro mol.l/h), the AUC of thiocyanate was higher in rats (846.5 micro mol.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.
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