The plant material was prepared

by chopping the leaves in a blender with the lowest amount of water possible (approximately 750 ml). All animals were closely monitored for any clinical disturbance. The two sheep dosed for 10 consecutive days were euthanized 24 h after the final dose for pathological study. After they were sacrificed, the sheep were necropsied, and samples from the liver, kidney, lungs, heart, spleen, rumen, omasum, abomasum and intestines were collected, fixed, and stored in 10% buffered formalin for histopathological examination. The paraffin-embedded sections were stained with H&E. All of the rats dosed with 1.0 ml of latex/kg body weight showed severe MLN0128 lethargy beginning 5–8 min after dosing and died within 2 h. No death or clinical signs of toxicity were observed in the rats from control group and dosed with 0, 0.1, 0.3 or 0.6 ml of latex/kg body weight. No macroscopic lesions were found in the necropsies of dead rats. The histological lesions were Selleckchem AZD8055 restricted to rats dosed with 1.0 ml of latex/kg body weight. Microscopic lesions in the hearts appeared as fibers separated by edematous fluid, and the rats exhibited subendocardic hemorrhages, multi-focal coagulation necroses of the muscular fibers evidenced by granular appearance of the sarcoplasm, distinct eosinophilic cytoplasm lacking transverse striations and presenting pyknotic or absent

nuclei (Fig. 1). Infiltration of mononuclear inflammatory

cells was observed between the cardiac fibers. Some muscle fibers presented basophilic granulation and prominent vacuolization of the sarcoplasm (Fig. 2). The livers showed diffuse vacuolization of the hepatocyte cytoplasm, marked sinusoidal congestion and small hemosiderin deposits in the parenchymal hepatocytes. The administration of C. procera leaves to sheep from all groups was responsible for tachycardia and transitory cardiac arrhythmias at auscultation 4 h after dosing. The necroscopic examination of sheep dosed with 60 g/kg per day for 10 days revealed mild ascites, exudates Osimertinib on the trachea, pulmonary edema, mild hemorrhage in the liver, hydropericardium, flaccid heart, ulcers on the omasum and kidneys presenting a pale juxtamedullary cortex. The histological examination of livers and hearts from the sheep revealed similar lesions to those observed in the rats, but the intensity of these lesions varied from mild to moderate. Congestion was observed in the kidneys and lungs. No lesions were found in the spleen, rumen, omasum, abomasum or intestine samples from these sheep. Our results demonstrate that C. procera is a cardiotoxic plant. The lesions promoted by exposure to C. procera latex and fresh leaves were different from those observed in other studies ( Mahmoud et al., 1979a, Mahmoud et al., 1979b, Pahwa and Chatterjee, 1988 and Singhal and Kumar, 2009). The lesions promoted by C.