Nuehring L P, Rowland G N, Harrison L R, Cole R J, Dorner J W
Am J Vet Res. 1985 Aug;46(8):1670-6.
The subacute toxic effects of cyclopiazonic acid (CPA; given orally) were characterized in the dog (CPA was purified from cultures of Aspergillus flavus). Four groups of dogs were given CPA in gelatin capsules for 90 days at the following dosage levels: 0.05, 0.25, 0.5, and 1.0 mg/kg of body weight; a 5th group was used as controls. All dogs administered the 0.5 and 1.0 mg of CPA/kg dosages and 1 dog given the 0.25 mg of CPA/kg dosage died or were humanely killed before the scheduled termination of the study. Clinical signs of intoxication appeared 2 to 44 days after dosing was started and consisted of anorexia and, in 1 to 2 days, vomiting, diarrhea, pyrexia, dehydration, weight loss, and CNS depression. Grossly, the entire alimentary tract had diffuse hyperemia with focal areas of hemorrhage and ulceration. Other lesions were renal infarcts, necrotizing epididymitis, and ulcerative dermatitis. Microscopic lesions included ulceration, necrosis, vasculitis, lymphoid necrosis, karyomegaly in several organs, and decreased mitotic activity in intestinal crypt epithelium. Ulcerative and necrotic lesions were usually associated with vascular lesions. Clinical pathologic changes were leukocytosis, neutrophilia, lymphopenia, monocytosis, and increased serum alkaline phosphatase activity.
环匹阿尼酸(CPA;经口服给药)对犬的亚急性毒性作用已得到明确(CPA从黄曲霉培养物中纯化而来)。四组犬分别以以下剂量水平通过明胶胶囊给予CPA,持续90天:0.05、0.25、0.5和1.0毫克/千克体重;第五组用作对照。所有接受0.5和1.0毫克CPA/千克剂量的犬以及1只接受0.25毫克CPA/千克剂量的犬在预定研究结束前死亡或被人道处死。中毒的临床症状在给药开始后2至44天出现,包括食欲不振,1至2天后出现呕吐、腹泻、发热、脱水、体重减轻和中枢神经系统抑制。大体上,整个消化道出现弥漫性充血,伴有局部出血和溃疡区域。其他病变包括肾梗死、坏死性附睾炎和溃疡性皮炎。微观病变包括溃疡、坏死、血管炎、淋巴组织坏死、多个器官的核肿大以及肠隐窝上皮细胞有丝分裂活性降低。溃疡性和坏死性病变通常与血管病变相关。临床病理变化包括白细胞增多、中性粒细胞增多、淋巴细胞减少、单核细胞增多以及血清碱性磷酸酶活性升高。