Partial hepatectomy of marmoset: clinical and pathological effects and utility in microsomal enzyme analysis.
Liver biopsy based on a partial hepatectomy technique (shearing) was performed in 10 common marmosets (Callithrix jacchus). This is a preliminary study to evaluate the effects of drugs on hepatic microsomal enzymes: cytochrome P-450 and T4 uridine diphosphate glucuronyl transferase (T4-UDPGT), by comparing post-treatment values with pre-treatment values individually with a limited number of animals. The effects of the biopsy on clinical findings and liver pathology were evaluated during the first 5 post-surgical weeks. Although the plasma aspartate aminotransferase (AST) activities tended to decrease from 1 to 4 weeks post-surgery, no abnormality was noted in clinical sign, body weight, the hematocrit value or other blood chemical values. At necropsy, adhesion of the sheared site of the liver to the parietal peritoneum or the small intestine was evident in 2 of the 4 marmosets. Microscopic examination revealed focal fibrosis in the liver, but it was localized around the sheared site. Based on the above results, it was concluded that liver biopsy must be performed more than one month before administration of the drug to be tested. The biopsy samples and the whole liver samples obtained at autopsy were subjected to analysis of microsomal protein content, cytochrome P-450 content and T4-UDPGT activity. In comparison with the values from the whole liver samples, those from the biopsy samples showed no significant difference. Furthermore, there was a significant correlation rather than difference between matched values. This suggested that partial hepatectomy is a useful method for obtaining pretreatment values in liver biochemistry to evaluate the effects of drug-treatment in individual animals.
Kurata
Y
Y
Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan.
Makinodan
F
F
Matsumoto
J
J
Toyota
N
N
Tanaka
K
K
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight; D002144:Callithrix; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006400:Hematocrit; D006498:Hepatectomy; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000473:pathology* / Q000601:surgery; D008107:Liver Diseases / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009929:Organ Size; D000267:Tissue Adhesions / Q000473:pathology
D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; C117189:thyroxine-UDP-glucuronosyltransferase; D014453:Glucuronosyltransferase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase