Halothane-induced Hepatic Necrosis in Triiodothyronine-pretreated Rats

Wood, Margaret; Berman, M. L.; Harbison, Raymond D.; Hoyle, Peter C.; Phythyon, James M.; Wood, A. J. J.

doi:10.1097/00000542-198006000-00003

Cited by 57 publications

(14 citation statements)

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“…107,108 In the case of acute iron overload in hyperthyroid animals, the enhanced hepatotoxicity observed also is associated with the severe oxidative stress status established in the tissue, that is related to an impairment of Kupffer cell phagocytosis and particleinduced respiratory burst activity. 109 In agreement with these studies, thyroid hormone-induced sensitization to hepatotoxicity also has been reported for halothane, [110][111][112] isoflurane and enflurane, 111 carbon tetrachloride, 113 thioacetamide, 114 1,1-dichloroethylene, 115,116 and chloroform. 117 Moreover, a hypothyroid state induced by methimazole or PTU administration and thyroidectomy substantially reduces the development of liver injury associated with thioacetamide intoxication, 114 cold organ storage in liver transplantation, 108 or that produced by the exposure of rats chronically treated with ethanol to low O 2 tensions.…”

Section: Thyroid Hormone-induced Oxidative Stress In Mansupporting

confidence: 78%

Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences

Videla

2000

Redox Report

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Section: Thyroid Hormone-induced Oxidative Stress In Mansupporting

confidence: 78%

Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences

Videla

2000

Redox Report

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“…35 This differs from the phenobarbitone model in that hypoxia is not a prerequisite for liver damage and the reductive pathway is not implicated. "6 It has been suggested, however, that liver cell necrosis is mainly due to hypoxic damage as a result of induced hypermetabolism of centrilobular cells and anaesthetic depression of splanchnic blood flow.37…”

Section: Triiodothyronine Modelmentioning

confidence: 97%

Halothane anaesthesia and liver damage.

Neuberger¹,

Williams²

1984

BMJ

102

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A recent experience of the senior author when addressing a meeting of anaesthetists prompted this review, since it was apparent that there was still considerable disagreement between hepatologists and anaesthetists over the association between liver cell damage and halothane anaesthesia and the measures by which the risk could be minimised. Although during the 1960s and 1970s the evidence was hotly debated, there has since been increasing acceptance, both clinical and experimental, of a strong prima facie case for an association.'" Two, probably distinct, forms of liver damage have been defined.'2 Serum aminotransferase activities are raised in up to a fifth of patients anaesthetised with halothane during the first and second postoperative weeks (type I). Such minor forms of liver injury are to be distinguished from the rare occurrence of massive liver cell necrosis (type II).Three well controlled studies of minor reactions have been reported from Britain.s 6 8 Significant rises in serum aspartate aminotransferase (AST) activity during the postoperative period were found only in those patients receiving halothane,5 and these activities were significantly higher than in those receiving trichloroethylene.6 Abnormalities in liver function were not always apparent until the second postoperative week. Rises of serum amunotransterase activity were also greater in those receiving halothane than with enflurane,8 and obese women were more likely to develop abnormalities.Most patients who have developed massive necrosis have had a previous and milder reaction to halothane. Nevertheless, the frequency of minor abnormalities (up to 20%) and the very low incidence of massive necrosis make it clear that minor reactions are not necessarily followed by more severe effects. There is no way of predicting which patients will follow this course.We have seen now 48 patients with otherwise unexplained massive liver cell necrosis after halothane anaesthesia referred to the liver unit over the period January 1965 to December 1983. In each of the 48 patients other possible causes of liver damage were excluded, including exposure to hepatotoxic agents, sepsis, hypotension during surgery, and infection with hepatitis A and B, cytomegalovirus, and Epstein-Barr virus. In no case was there evidence of pre-existing liver disease.Thirty one of the 48 patients were women, giving a female to male ratio of 1 8:1. Ages ranged from 21 to 76 years (median 57 years), contrasting appreciably with the much younger age distribution of patients with fulminant viral hepatitis (fig 1). In comparison with the age distribution of patients undergoing anaesthesia in England and Wales, as given in the Hospital Inpatient Enquiry,'3 the patients with halothane hepatotoxicity are in a slightly older age group. Sixty eight per cent of the patients were obese and there was a history of allergy to other drugs in one third of them.The interval between the last exposure to halothane and the onset of jaundice ranged from two to 26 days, with a median of five days, and i...

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“…For histology, liver tissue was fixed in 10% neutral buffered formalin and sections stained with hematoxylineosin (HE)to determine morphological changes. HEstained liver sections were examined under low-power (100ϫ) microscopy and necrosis graded using a system 23 previously described: 0, no lesion present; 1/2, individual necrotic cells seen at the first cell layer adjacent to the central vein, and hyaline degeneration present; 1, necrotic cells extending two or three cell layers from the central veins; 2, necrotic cells extending three to six cell layers from the central veins, but limited in peripheral distribution; 3, the same as 2, but with necrosis extending from one central vein to another; 4, more severe than 3, with extensive centrilobular necrosis throughout the section. An overall score was computed for each liver section based on assessment of five lobules.…”

Section: Animals Treatments and Assays For Serum Altmentioning

confidence: 99%

Neutrophil depletion protects against murine acetaminophen hepatotoxicity†‡

et al. 2006

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We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)-induced liver injury by producing interferon gamma (IFN-␥) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity. C57BL/6 mice were given an intraperitoneal toxic dose of APAP (500 mg/kg), which caused severe acute liver injury characterized by significant elevation of serum ALT, centrilobular hepatic necrosis, and increased hepatic inflammatory cell accumulation. Flow cytometric analysis of isolated hepatic leukocytes demonstrated that the major fraction of increased hepatic leukocytes at 6 and 24 hours after APAP was neutrophils (Mac-1 ؉ Gr-1 ؉ ). Depletion of neutrophils by in vivo treatment with anti-Gr-1 antibody (RB6-8C5) significantly protected mice against APAP-induced liver injury, as evidenced by markedly reduced serum ALT levels, centrilobular hepatic necrosis, and improved mouse survival. The protection was associated with decreased FasL-expressing cells, cytotoxicity against hepatocytes, and respiratory burst in hepatic leukocytes. In intracellular adhesion molecule (ICAM)-1-deficient mice, APAP caused markedly reduced liver injury when compared with wild-type mice. The marked protection in ICAM-1-deficient mice was associated with decreased accumulation of neutrophils in the liver. Hepatic GSH depletion and APAP-adducts showed no differences among the antibody-treated, ICAM-1-deficient, and normal mice. In conclusion, accumulated neutrophils in the liver contribute to the progression and severity of APAP-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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Halothane-induced Hepatic Necrosis in Triiodothyronine-pretreated Rats

Cited by 57 publications

References 0 publications

Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences

Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences

Halothane anaesthesia and liver damage.

Neutrophil depletion protects against murine acetaminophen hepatotoxicity†‡

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