Behavioral and biochemical characterization of rats treated chronically with thioacetamide: proposal of an animal model for hepatic encephalopathy associated with cirrhosis

Kawai, Hiroshi; Ishibashi, Takuya; Kudo, Naomi; Kawashima, Yasunaru; Mitsumoto, Atsushi

doi:10.2131/jts.37.1165

Cited by 23 publications

(18 citation statements)

References 42 publications

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“…The statistically significant increase of the GGT concentrations is due to the metabolic consequence of TAA induced dysmetabolism leading to severe hepatic steatosis, of which GGT is a marker. These results are in accordance with many investigations on thioacetamide -induced liver fibrosis and cirrhosis in rats (Gu et al 2011a;Gu et al 2011b;Kawai et al 2012;Laleman et al 2006).…”

Section: Discussionsupporting

confidence: 92%

Effects of lactulose and silymarin on liver enzymes in cirrhotic rats

Pour

Mirazi

Alaei

et al. 2017

Can. J. Physiol. Pharmacol.

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Silymarin, a mixture of antihepatotoxic flavonolignans used in the treatment of liver diseases, and lactulose, a nonabsorbable synthetic disaccharide, were investigated to analyze their probable synergic and healing effects in a hepatic cirrhotic rat model. Liver damage was induced by the administration and subsequent withdrawal of thioacetamide. The significant decrease in liver enzymes and malondialdehyde levels confirmed the curative effects of silymarin and lactulose. In the silymarin + lactulose group, liver enzyme and malondialdehyde levels were significantly reduced compared with those in the thioacetamide group. All treatments led to liver regeneration and triggered enhanced regeneration. Silymarin and lactulose alone or in combination have potent curative effects and reduce thioacetamide-induced liver damage.

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Section: Discussionsupporting

confidence: 92%

Effects of lactulose and silymarin on liver enzymes in cirrhotic rats

Pour

Mirazi

Alaei

et al. 2017

Can. J. Physiol. Pharmacol.

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“…Increased brain ammonia levels and neuroinflammation are also present in rats with thioacetamide (TAA)‐induced liver injury, associated with reduced scores in the novel object recognition task . Chrysin, a natural flavonoid with anti‐inflammatory properties, improved thioacetamide‐induced motor incoordination and cognitive deficits and attenuated hyperammonaemia and neuroinflammation …”

Section: Animal Models Of Mhe and Chronic Hyperammonaemia Also Show Nmentioning

confidence: 99%

“…45 Increased brain ammonia levels and neuroinflammation are also present in rats with thioacetamide (TAA)-induced liver injury, 46 associated with reduced scores in the novel object recognition task. 47 Chrysin, a natural flavonoid with antiinflammatory properties, improved thioacetamide-induced motor incoordination and cognitive deficits and attenuated hyperammonaemia and neuroinflammation. 48 Rats with TAA-induced acute liver failure show increased CCL2 (also known as MCP-1) expression and microglia activation in the cerebral cortex and CCL2 receptors inhibition improves neurological score and reduces cortical microglia activation.…”

Section: Infiltration Of Lymphocytes In Meningesmentioning

confidence: 99%

Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications

et al. 2019

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Several million patients with liver cirrhosis suffer minimal hepatic encephalopathy (MHE), with mild cognitive and coordination impairments that reduce their quality of life and life span. Hyperammonaemia and peripheral inflammation act synergistically to induce these neurological alterations. We propose that MHE appearance is because of the changes in peripheral immune system, which are transmitted to brain, leading to neuroinflammation that alters neurotransmission leading to cognitive and motor alterations. We summarize studies showing that MHE in cirrhotic patients is associated with alterations in the immune system and that patients died with HE show neuroinflammation in cerebellum, with microglial and astrocytic activation and Purkinje cell loss. We also summarize studies in animal models of MHE on the role of peripheral inflammation in neuroinflammation induction, how neuroinflammation alters neurotransmission and how this leads to cognitive and motor alterations. These studies identify therapeutic targets and treatments that improve cognitive and motor function. Rats with MHE show neuroinflammation in hippocampus and altered NMDA and AMPA receptor membrane expression, which impairs spatial learning and memory. Neuroinflammation in cerebellum is associated with altered GABA transporters and extracellular GABA, which impair motor coordination and learning in a Y maze. These alterations are reversed by treatments that reduce peripheral inflammation (anti‐TNFα, ibuprofen), neuroinflammation (sulphoraphane, p38 inhibitors), GABAergic tone (bicuculline, pregnenolone sulphate) or increase extracellular cGMP (sildenafil or cGMP). The mechanisms identified would also occur in other chronic diseases associated with inflammation, aging and some mental and neurodegenerative diseases. Treatments that improve MHE may also be beneficial to treat these pathologies.

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“…These models, developed to mimic type C HE, try to reproduce the clinical characteristics of chronic cirrhosis and its cognitive and motor symptoms, and they require obstruction of the bile duct [12][13][14][15][16] or the administration of hepatotoxins, such as carbon tetrachloride or thioacetamide (TAA) [17]. Several studies have reported that the chronic oral administration of TAA causes an impairment in associative learning and spatial memory in rats [18][19][20][21][22].…”

mentioning

confidence: 99%