Characteristics of nitrogen metabolism in rats with thioacetamide-induced liver cirrhosis

Masumi, Shigeru; Moriyama, Mitsuaki; Kannan, Yukiko; Ohta, Mitsuaki; Koshitani, Osamu; Sawamoto, Osamu; Toyoshima, Shigeki; Ishikawa, Kinya; Miyoshi, Masafumi; Sugano, Tsukasa

doi:10.1016/s0300-483x(98)00148-6

Cited by 5 publications

(10 citation statements)

References 18 publications

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“…The presence of Alzheimer type II astrocytosis (predominantly in the cerebral cortex), behavioural abnormalities associated with cognitive dysfunction are observed, including drowsiness, decreased wakefulness, impaired attentiveness, decreased grooming and exploratory behaviour 96 together with increased blood and brain ammonia 94,95 . In addition, many studies have administered 12 weeks of TAA by its addition to the drinking water 97‐102 . TAA‐induced type C HE models in mice are lacking.…”

Section: Current Animal Models Of Hementioning

confidence: 99%

2021 ISHEN guidelines on animal models of hepatic encephalopathy

DeMorrow

Cudalbu

Davies

et al. 2021

Liver International

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This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non‐alcoholic fatty liver disease; the most common etiologies of chronic liver disease.

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Section: Current Animal Models Of Hementioning

confidence: 99%

2021 ISHEN guidelines on animal models of hepatic encephalopathy

DeMorrow

Cudalbu

Davies

et al. 2021

Liver International

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“…Thioacetamide (TAA)-induced acute HE in rats was used in this study [36][37][38][39][40][41][42][43][44]. The TAA-treated rat model of Type A HE has been well-established relative to the clinical status and liver and brain function [36][37][38][39][40][41][42][43][44]. It should be highlighted that this is the most widely used animal model to study acute HE.…”

Section: Type a He In Ratsmentioning

confidence: 99%

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol

Tong,

Hussain,

Shamaladevi

et al. 2024

Biology

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Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA’s brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.

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“…12, 13-17), urea cycle (nos. [18][19][20], gluconeogenic amino acid oxidation pathways (nos. 25-27, 30-32, 34, 35, 40-48, 50), ␤-oxidation (no.…”

Section: Gross Livermentioning

confidence: 99%

“…16,17 These approaches, which were largely unsuccessful, aimed at counteracting the observed shifts in metabolite levels in the systemic circulation; however, systemic changes in metabolite levels do not solely reflect alterations in liver function, but also changes in whole-body metabolism. Therefore, a better understanding of which pathways are directly affected in the liver during hepatic failure may provide a rational basis for developing a nutritional support or other nonsurgical, conventional medical therapy.To characterize the metabolic state of the liver in the absence of systemic effects, previous investigators have used isolated perfused liver systems to study amino acid metabolism in cirrhotic rats [18][19][20][21] and gluconeogenesis in the D-galactosamine-treated FHF rat model. 22 These studies were limited by the small number of parameters measured, which prevented a more global and comprehensive analysis of the metabolic changes induced by FHF in the liver.…”

mentioning

confidence: 99%

“…To characterize the metabolic state of the liver in the absence of systemic effects, previous investigators have used isolated perfused liver systems to study amino acid metabolism in cirrhotic rats [18][19][20][21] and gluconeogenesis in the D-galactosamine-treated FHF rat model. 22 These studies were limited by the small number of parameters measured, which prevented a more global and comprehensive analysis of the metabolic changes induced by FHF in the liver.…”

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confidence: 99%

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Intrahepatic amino acid and glucose metabolism in a ?-galactosamine–induced rat liver failure model

et al. 2001

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A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D-galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid-supplemented Eagle minimal essential medium containing 3% wt/ vol bovine serum albumin and oxygenated with 95% O 2 /5% CO 2 . Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to ␣-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function. (HEPATOLOGY 2001;34:360-371.)Since the late 1980s, orthotopic liver transplantation has become the only widely accepted treatment for fulminant hepatic failure (FHF). [1][2][3][4] Because of the severe shortage in donor organs, various alternatives aimed at providing a "substitute" liver, such as xenogeneic whole liver perfusion 5 and extracorporeal bioartificial liver devices, 6,7 are being developed. Such systems, which can be used as a bridge to transplantation or provide temporary relief during the most acute phase of hepatic failure, are promising, although technically complex and expensive. It has been hypothesized that hepatic encephalopathy may result from the elevation of circulating levels of putative toxins such as ammonia, mercaptans, short-chain fatty acids, [8][9][10] and an abnormal amino acid profile. [11][12][13] In FHF patients, alterations in amino acid concentrations in systemic plasma have been characterized by several investigators, 14,15 which led to the use of solutions rich in branchedchain amino acids (BCAA) for the treatment of hepatic encephalopathy. 16,17 These approaches, which were largely unsuccessful, aimed at counteracting the observed shifts in metabolite levels in the systemic circulation; however, systemic changes in metabolite levels do not solely reflect alterations in liver function, but also changes in whole-b...

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Characteristics of nitrogen metabolism in rats with thioacetamide-induced liver cirrhosis

Cited by 5 publications

References 18 publications

2021 ISHEN guidelines on animal models of hepatic encephalopathy

2021 ISHEN guidelines on animal models of hepatic encephalopathy

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol

Intrahepatic amino acid and glucose metabolism in a ?-galactosamine–induced rat liver failure model

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