Single dose intravenous thioacetamide administration as a model of acute liver damage in rats.
Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-alpha and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.
Chen
Tse-Min
TM
Division of Laboratory Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan.
Subeq
Yi-Maun
YM
Lee
Ru-Ping
RP
Chiou
Tzyy-Wen
TW
Hsu
Bang-Gee
BG
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000032:analysis; D002273:Carcinogens / Q000008:administration & dosage* / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D023421:Models, Animal; D016328:NF-kappa B / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D013853:Thioacetamide / Q000008:administration & dosage* / Q000633:toxicity; D013995:Time; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
D002273:Carcinogens; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide; D052247:Nitric Oxide Synthase Type II; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin