Acute Hepatotoxicity of Adriamycin-Oxidized Dextran (ADM-OXD) in Rat

Kawabata, Yoshinari; Ando, Nobuaki; Koshiba, Hiroshi; Kashihara, Junichi; Sonoda, T.; Nohara, Masasi; Wakamatsu, Chiemi; Tsubota, Hiroko; Munechika, Koji; Iwai, Masakazu

doi:10.1293/tox.6.1s

Cited by 3 publications

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“…However, hepatotoxicity is induced specifically by ADM-OXD5, 6. It has been reported that the conjugate form has neither pharmacological nor toxicological action, but free ADM liberated from the conjugate within tissue shows cell toxicity7.…”

Section: Introductionmentioning

confidence: 99%

Effect of adriamycin-oxidized dextran(ADM-OXD) on Kupffer cell.

et al. 1994

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Abstract:The effect of adriamycin-oxidized dextran (ADM-OXD) on hepatic macrophage (Kupffer cell) was studied using male Wistar rats. Kupffer cell function was measured using as an index the clearance rate from circulating blood of extrinsic carbon particles (phagocytic index). This index fell markedly from soon after a single intravenous injection of ADM-OXD at a dose of 30 or 60mg/kg in terms of ADM content. Carbon uptake in periportal Kupffer cells, evaluated using HE stained liver sections, was markedly lower in ADM-OXD treated animals than in control animals. The relationship between damage to parenchymal cells and to sinusoidal lining cells, especially Kupffer cells, was monitored morphologically and biochemically for 48 hours after a single injection at a dose of 60mg/kg. Serum biochemical changes showing parenchymal cell dysfunction and morphologically regressive changes such as diffuse centrilobular necrosis were observed in pronounced form at 48 hours. Kupffer cells, in contrast, were found to be degenerative or necrotic ultrastructurally as early as at 8 hours. Immunohistochemically, the number of ED2-positive Kupffer cells in the periportal area decreased from 8 hours. Activity of serum cathepsin D, thought to be leaked from Kupffer cell lysosomes, was elevated from an early stage. It was judged that Kupffer cell damage preceded parenchymal cell damage. Pretreatment with estrogen, which has a proliferative action on hepatic macrophages, mitigated ADM OXD-induced hepatotoxicity. Damage to sinusoidal lining cells (Kupffer cells) would therefore seem to participate closely in the onset of parenchymal cell damage. (J Toxicol Pathol 7: 199-210, 1994)

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Section: Introductionmentioning

confidence: 99%