Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

• Published in: World journal of gastroenterology : WJG Vol. 23; no. 42; pp. 7572 - 7583
• Main Authors: Feng, Lei, Cai, Lei, He, Guo-Lin, Weng, Jun, Li, Yang, Pan, Ming-Xin, Jiang, Ze-Sheng, Peng, Qing, Gao, Yi
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.11.2017
• Subjects: Basic Study; Artificial liver support systems; Acute liver failure; D-galactosamine; Intracranial pressure; Cynomolgus monkey
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i42.7572

AIM To establish a simplified, reproducible D-galactosamineinduced cynomolgus monkey model of acute liver failure having an appropriate treatment window. METHODS Sixteen cynomolgus monkeys were randomly dividedinto four groups(A, B, C and D) after intracranial pressure(ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05(24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded. RESULTS Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBi L, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor(TNF)-α, interleukin(IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups(P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.CONCLUSION We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.