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Titolo:
Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8transgenic mice
Autore:
Horiguchi, H; Harada, A; Oguma, E; Sato, M; Homma, Y; Kayama, F; Fukushima, M; Matsushima, K;
Indirizzi:
Jichi Med Sch, Div Environm Immunol & Toxicol, Dept Hlth Sci, Minami Kawachi, Tochigi 3290498, Japan Jichi Med Sch Minami Kawachi Tochigi Japan 3290498 Tochigi 3290498, Japan Jichi Med Sch, CREST, Dept Hlth Sci, Minami Kawachi, Tochigi 3290498, Japan Jichi Med Sch Minami Kawachi Tochigi Japan 3290498 Tochigi 3290498, Japan Fukushima Med Univ, Fac Med, Dept Publ Hlth, Fukushima 9601295, Japan Fukushima Med Univ Fukushima Japan 9601295 lth, Fukushima 9601295, Japan Kanazawa Univ, Sch Med, Dept Hyg, Kanazawa, Ishikawa 920, Japan Kanazawa Univ Kanazawa Ishikawa Japan 920 , Kanazawa, Ishikawa 920, Japan Univ Tokyo, Sch Med, CREST, Bunkyo Ku, Tokyo 113, Japan Univ Tokyo TokyoJapan 113 , Sch Med, CREST, Bunkyo Ku, Tokyo 113, Japan Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 113, Japan Univ Tokyo Tokyo Japan 113 Mol Prevent Med, Bunkyo Ku, Tokyo 113, Japan Fukushima Med Univ, Inst Biomed Sci, Fukushima 9601295, Japan Fukushima Med Univ Fukushima Japan 9601295 Sci, Fukushima 9601295, Japan Tokushima Bunri Univ, Fac Pharmaceut Sci, Yamashiro, Tokushima 7708514, Japan Tokushima Bunri Univ Yamashiro Tokushima Japan 7708514 ima 7708514, Japan
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 3, volume: 163, anno: 2000,
pagine: 231 - 239
SICI:
0041-008X(20000315)163:3<231:CAHIIE>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; LIVER-INJURY; INDUCED HEPATOTOXICITY; RAT HEPATOCYTES; ACUTE EXPOSURE; MESSENGER-RNA; FACTOR-ALPHA; INDUCTION; CYTOTOXICITY;
Keywords:
cadmium; liver; interleukin-8; neutrophil; transgenic mouse;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Horiguchi, H Jichi Med Sch, Div Environm Immunol & Toxicol, Dept Hlth Sci,3311-1 Yakushiji, Minami Kawachi, Tochigi 3290498, Japan Jichi Med Sch 3311-1 Yakushiji Minami Kawachi Tochigi Japan 3290498
Citazione:
H. Horiguchi et al., "Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8transgenic mice", TOX APPL PH, 163(3), 2000, pp. 231-239

Abstract

It is reported repeatedly that severe hepatocellular necrosis along with infiltration of neutrophils occurs after acute cadmium exposure. Neutrophils, which migrate by the gradient of chemoattractants such as interleukin-8, are believed to play an important role in inflammation at the damaged sites. To investigate whether neutrophils aggravate or repair the liver injury induced by cadmium, we checked the hepatotoxic effects of cadmium on human interleukin-8 transgenic mice (hIL-8Tg), which overexpressed IL-8 and displayed an inability of neutrophil migration resulting from both the lack of chemotactic gradient and the downregulation of L-selectin on the surface of neutrophils. A significantly lower survival rate was observed in hIL-8Tg compared with wildtype mice after subcutaneous administration of cadmium. Evident liver injury characterized by abrupt increases in plasma GOT and GPT levels was found in hIL-8Tg at 18 h after cadmium administration. Histological examinations, including H & E staining and esterase staining, revealed the infiltration of numerous neutrophils into the damaged liver tissues in wild-type mice, and the inhibition of the neutrophil migration into the liveras well as enhanced hepatocellular necrosis in hIL-8Tg. Peripheral white blood cell and polymorphonuclear cell counts increased and reached their peaks at 12 h after cadmium administration in wild-type mice, whereas the increase in blood leukocyte counts was delayed in hIL-8Tg. There was no significant difference in the amounts of cadmium accumulated in liver and kidneys between wild-type mice and hIL-8Tg. In conclusion, an acute cadmium hepatotoxic effect was exacerbated in hIL-8Tg resulting from inhibited neutrophil migration, suggesting that migrated neutrophils can prevent aggravation of liver injury by acute cadmium administration. (C) 2000 Academic Press.

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Documento generato il 03/07/20 alle ore 01:30:36