α-Naphthylisothiocyanate Causes Neutrophils to Release Factors That Are Cytotoxic to Hepatocytes

Hill, Dwayne A.; Roth, Robert A.

doi:10.1006/taap.1997.8314

Cited by 38 publications

(28 citation statements)

References 19 publications

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“…Because of this they suggested that neutrophil in®ltration is a major aspect of ANIT-induced liver injury. Also, it has been demonstrated under in vitro conditions that ANIT stimulates neutrophils to release superoxide anions and proteolytic enzymes that are toxic to hepatic parenchyma cells [Roth and Hewett, 1990;Hill and Roth, 1998]. However, Dahm et al [1991] found that in rats pretreated with a combination of the antioxidative superoxide dismutase and catalase, the degree of ANIT-induced hepatic damage is not attenuated.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the protective effects of melatonin and related indoles against ?-naphthylisothiocyanate-induced liver injury in rats

et al. 2001

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The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage.

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Section: Discussionmentioning

confidence: 99%

Characterization of the protective effects of melatonin and related indoles against ?-naphthylisothiocyanate-induced liver injury in rats

et al. 2001

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“…To do so we used α-naphthylisothiocyanate (ANIT), a well described hepatotoxicant that induces hallmark responses in the mammalian biliary system, namely: cytotoxicity in biliary epithelium of bile ductules and ducts (e.g. impaired mitochondrial function, necrosis), cholestasis (Hill and Roth 1998;Orsler et al 1999;Waters et al 2002;Woolley et al 1979), and biliary tree arborization (biliary epithelial cell hyperplasia) (Alpini et al 1992;Connolly et al 1988;Masyuk et al 2003). Because biliary toxicity and cholestasis are poorly understood in piscine species, and because we now understand the medaka hepatobiliary system to be more similar to mammalian liver architecture than previously considered (Hardman et al 2007b), we considered ANIT good toxicant for investigation of comparative hepatology.…”

Section: Introductionmentioning

confidence: 99%

Non invasive high resolution in vivo imaging of α-naphthylisothiocyanate (ANIT) induced hepatobiliary toxicity in STII medaka

et al. 2008

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A novel transparent stock of medaka (Oryzias latipes; STII), homozygous recessive for all four pigments (iridophores, xanthophores, leucophores, melanophores), permits transcutaneous, high resolution ( < 1μm) imaging of internal organs and tissues in living individuals. We applied this model to in vivo investigation of α-napthylisothiocyanate (ANIT) induced hepatobiliary toxicity. Distinct phenotypic responses to ANIT involving all aspects of intrahepatic biliary passageways (IHBPs), particularly bile preductular epithelial cells (BPDECs), associated with transitional passageways between canaliculi and bile ductules, were observed. Alterations included: attenuation/ dilation of bile canaliculi, bile preductular lesions, hydropic vacuolation of hepatocytes and BPDECs, mild BPDEC hypertrophy, and biliary epithelial cell (BEC) hyperplasia. Ex vivo histological, immunohistochemical, and ultrastructural studies were employed to aid in interpretation of, and verify, in vivo findings. 3D reconstructions from in vivo investigations provided quantitative morphometric and volumetric evaluation of ANIT exposed and untreated livers. The findings presented show for the first time in vivo evaluation of toxicity in the STII medaka hepatobiliary system, and, in conjunction with prior in vivo work characterizing normalcy, advance our comparative understanding of this lower vertebrate hepatobiliary system and its response to toxic insult.

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“…Neutrophils are equipped with a potent proteolytic apparatus, and they are capable of eliminating various proteins in a highly ecient manner (Lefkovits et al 1997). Cathepsin G and elastase are toxic to hepatocytes and cause hepatocellular damage in vitro (Hill and Roth 1998). These neutral proteases can be implicated in the disruption of the blood-brain barrier in rats (Armao et al 1997).…”

Section: Discussionmentioning

confidence: 98%

Neutrophil antiserum response to decrease in proteolytic activity in loaded rat muscle

Морозов¹,

Usenko

Рогозкин³

2001

European Journal of Applied Physiology

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The leukocytes that are found in skeletal muscles after intense muscular activity have been shown to infiltrate areas of injury in skeletal muscle tissue. We believe that leukocyte enzymes, which appear in the tissue after the degranulation or destruction of leukocytes, could play a role in tissue enzyme activities. Neutrophil proteinases were investigated. Histological data provided evidence of rat muscular tissue infiltration by leukocytes after intense physical loading. To reduce the influx of leukocytes in rat muscles, a rabbit antiserum against rat peritoneal leukocytes was injected into rats after muscle loading. This resulted in a reduction in muscle cytosol proteolytic activity as compared to control animals (who received saline injections). The levels of proteolytic activities of media conditioned by the soleus muscle isolated from antiserum-treated rats were also reduced. These data provide evidence that the increase in proteolytic activity observed in rat skeletal muscles after physical loading is partially induced by neutrophil proteinases.

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α-Naphthylisothiocyanate Causes Neutrophils to Release Factors That Are Cytotoxic to Hepatocytes

Cited by 38 publications

References 19 publications

Characterization of the protective effects of melatonin and related indoles against ?-naphthylisothiocyanate-induced liver injury in rats

Characterization of the protective effects of melatonin and related indoles against ?-naphthylisothiocyanate-induced liver injury in rats

Non invasive high resolution in vivo imaging of α-naphthylisothiocyanate (ANIT) induced hepatobiliary toxicity in STII medaka

Neutrophil antiserum response to decrease in proteolytic activity in loaded rat muscle

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