Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7572
Peer-review started: August 24, 2017
First decision: September 13, 2017
Revised: September 17, 2017
Accepted: October 17, 2017
Article in press: October 17, 2017
Published online: November 14, 2017
To establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window.
Sixteen cynomolgus monkeys were randomly divided into 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.
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, TBiL, 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.
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.
Core tip: This is an article about a novel D-galactosamine-induced cynomolgus monkey model of acute liver failure (ALF). In this study, we used small saphenous vein puncture instead of jugular vein intubation for different doses of D-gal administration, which not only effectively avoided the trauma caused by intubation, but also significantly reduced the anesthesia time and greatly improved the convenience of operation. This study concluded that a simplified, reproducible D-gal-induced large-animal ALF model with an appropriate treatment window had been established successfully, which is suitable for assessing the safety and efficacy of artificial liver support systems, studying the pathogenesis of ALF, and developing new drugs.