Engelhardt J A, Carlton W W, Rebar A H, Hayes A W
Department of Veterinary Microbiology, Pathology and Public Health, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
Food Chem Toxicol. 1987 Nov;25(11):843-53. doi: 10.1016/0278-6915(87)90263-8.
The LD50 for rubratoxin B dissolved in dimethylsulphoxide and administered to Mongolian gerbils by ip injection was 2.0 (2.26-1.77) mg/kg body weight. The gross alterations observed at autopsy were pallor and mottling of the kidneys and liver and congestion of the spleen. The histopathological alterations seen were renal tubular degeneration and necrosis, degenerative changes in hepatocytes, and congestion of the spleen. The morphopathogenesis of lesions after a single ip LD50 dose was evaluated in a second study. The histopathological alterations that were observed were focal degeneration and necrosis of hepatocytes and renal tubular degeneration and necrosis. Hepatic lesions were observed in gerbils killed between 2 and 12 hr after dosing and included multifocal cytoplasmic vacuolation and coagulative necrosis of hepatocytes. The renal lesions were first observed 2 hr after dosing and increased to maximum severity at 40 hr after dosing. Tubular regeneration accompanied ongoing tubular necrosis at the end of the test period. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were increased 4 hr after dosing, peaked at 24 hr and remained elevated to the end of the test period. Serum K+ concentration was increased 16 hr after dosing and remained elevated to the end of the test period. In a third study, rubratoxin B was administered ip once daily for 7 days at doses of 25, 50 or 75% of the ip LD50. Toxicity was dose related and cumulative with multiple doses. Histopathological alterations included renal tubular degeneration and necrosis, mild tubular dilation and focal necrosis of hepatocytes. In a fourth study, rubratoxin B was administered ip at a dose of 25% of the ip LD50 once daily for 7 days. Histopathological alterations included renal tubular degeneration, mild renal tubular dilation and focal necrosis of hepatocytes. Activities of AST and ALT in serum were slightly increased after multiple doses of rubratoxin B. Results of urinalysis indicated hepatic and renal tubular damage.
溶解于二甲基亚砜并通过腹腔注射给予蒙古沙鼠的红曲霉素B的半数致死量（LD50）为2.0（2.26 - 1.77）毫克/千克体重。尸检时观察到的大体变化为肾脏和肝脏苍白、出现斑点以及脾脏充血。所见的组织病理学变化为肾小管变性和坏死、肝细胞变性改变以及脾脏充血。在第二项研究中评估了单次腹腔注射LD50剂量后病变的形态发病机制。观察到的组织病理学变化为肝细胞局灶性变性和坏死以及肾小管变性和坏死。在给药后2至12小时处死的沙鼠中观察到肝脏病变，包括肝细胞多灶性胞质空泡化和凝固性坏死。肾脏病变在给药后2小时首次观察到，并在给药后40小时达到最大严重程度。在试验期结束时，肾小管再生伴随着持续的肾小管坏死。给药后4小时血清中天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的活性升高，在24小时达到峰值，并一直升高到试验期结束。给药后16小时血清钾离子（K +）浓度升高，并一直升高到试验期结束。在第三项研究中，红曲霉素B以腹腔注射LD50的25%、50%或75%的剂量每日给药一次，持续7天。毒性与剂量相关且具有多剂量累积性。组织病理学变化包括肾小管变性和坏死、轻度肾小管扩张以及肝细胞局灶性坏死。在第四项研究中，红曲霉素B以腹腔注射LD50的25%的剂量每日给药一次，持续7天。组织病理学变化包括肾小管变性、轻度肾小管扩张以及肝细胞局灶性坏死。多次给予红曲霉素B后，血清中AST和ALT的活性略有升高。尿液分析结果表明存在肝脏和肾小管损伤。
