title: Immunohistochemical detection of polyunsaturated fatty acid oxidation markers in acetaminophen-induced liver injury in rats.
abstract: To clarfity whether polyunsaturated fatty acid (PUFA) oxidation is involved in the mechanism of acetaminophen (APAP)-induced apoptotic cell death, the production and localization of PUFA oxidation markers N(ε)-propanoyl-modified lysine, N(ε)-hexanoyl-modified lysine, 4-hydroxyhexenal-modified histidine and crotonaldehyde-modified lysine were evaluated in the development of APAP-induced liver injury. The immunoexpression of these markers in the liver was examined up to 24 hr post-APAP intraperitoneal injection in rats (1 g/kg body weight). The histopathological changes in the liver appeared 3 hr after APAP injection and became exacerbated with time. Proapoptotic protein Bax immunoreactivity was first detected in the degenerative hepatocytes 3 hr after the injection and areas positively immunostained for Bax reached a peak level at 6 hr, and then decreased at 12 and 24 hr. There was a significant increase in the TUNEL-positive rate at 12 and 24 hr. Immunohistological expression of all these oxidation markers was first detected in the degenerative hepatocytes 3 hr after the injection, and earlier than the occurrence of hepatocyte apoptosis. Immunohistochemical expression of these markers were observed in almost all degenerative hepatocytes 3-24 hr after APAP injection. Areas positively immunostained for these markers reached a peak level at 6 hr, and then decreased at 12 and 24 hr. The results thus suggest that the generation of PUFA oxidation markers may be the signature of early events preceding the induction of liver cell apoptosis and thus useful for early detection of oxidative stress-related liver cell injury.
authors: United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi, Yamaguchi 753–8515, Japan.
authors: Jing
authors: J
authors: Sun
authors: Akihiko
authors: A
authors: Sugiyama
authors: Shinsuke
authors: S
authors: Hisaka
authors: Yoji
authors: Y
authors: Kato
authors: Takashi
authors: T
authors: Takeuchi
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase