Establishment of acute liver failure model in Tibetan miniature pig and verified by dual plasma molecular adsorption system

• Published in: International journal of artificial organs Vol. 46; no. 3; pp. 141 - 152
• Main Authors: Wang, Yi, Zhou, Chenjie, Fu, Yu, Zhang, Linya, Liu, Shusong, Cai, Lei, Jiang, Zesheng, Xu, Xiaoping, Feng, Lei, Gao, Yi
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-03-2023; Wichtig Editore s.r.l
• Subjects: Adsorption; Ammonia; Ammonia - adverse effects; Animal models; Animals; Appetite loss; Blood; Blood levels; Body weight; D-Galactosamine; Debilitation; Disease Models, Animal; Galactosamine - toxicity; Hepatocytes; Jaundice; Lipopolysaccharides - adverse effects; Liver; Liver failure; Liver Failure, Acute - chemically induced; Liver Failure, Acute - therapy; Medical instruments; Morbidity; Necrosis; Necrosis - pathology; Survival; Swine; Swine, Miniature; Tibet; Tibet; DPMAS; Acute liver failure; Tibetan miniature pig; animal model; d-galactosamine
• ISSN: 0391-3988; 1724-6040
• DOI: 10.1177/03913988221145501

Background:
Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality rates. Animal models are important for research on ALF. This study aimed to establish a reproducible, Tibetan miniature pig model of D-galactosamine-induced ALF and verify it using a dual plasma molecular adsorption system (DPMAS).
Methods:
Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after catheterization. D-galactosamine (D-gal) at 0.45, 0.40, 0.35, and 0.35 g/kg body weight, respectively, was injected through the catheter. Group D was treated with DPMAS 48 h after D-gal administration. Vital signs and blood index values were recorded every 12 h after D-gal administration. H&E, TUNEL, Ki67, and Masson staining tests were performed.
Results:
After D-gal administration, Tibetan miniature pigs developed different degrees of debilitation, loss of appetite, and jaundice. Survival times of groups A, B, C, and D were 39.7 ± 5.9, 53.0 ± 12.5,61.3 ± 8.1, and 61 ± 7 h, respectively. Blood levels of ALT, AST, TBIL, ammonia, PT, and inflammation factors significantly increased compared with baseline levels in the different groups (Ps < 0.05). Pathological results revealed a clear liver cell necrosis positive correlation with D-gal dose. However, DPMAS did not increase the survival time in ALF, ammonia, or liver cell necrosis.
Conclusion:
We successfully established a reproducible Tibetan miniature pig model of d-galactosamine-induced ALF, and we believe that a dosage of 0.35 g/kg is optimal.