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Animal models, mainly murine, stay as a fundamental resource in diverse research pursuits, notably contributing to significant strides in discovering novel treatments for therapeutic applications. Preclinical assays must consider the existence of self-recovery mechanisms in the murine species to achieve a well-designed control group. This study focuses on unveiling the innate rapid regenerative capacity of rat liver by utilizing the thioacetamide-induced sub-chronic liver injury model. Employing histopathological, biochemical, and molecular liver function tests, we assessed the recovery of liver tissue functionality. Moreover, animals were housed with voluntary running wheels and locomotory activity was recorded and employed as an indirect index of overall animal recuperation. Remarkably, basal locomotory activity reestablished to normal levels only two weeks post-thioacetamide exposure. Our results raise vital considerations about the importance of temporal synchronicity in comparative assays to validate the real action of treatments, emphasizing the role of the rapid rat liver endogenous self-recovery.
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SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.
La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.
Assuntos
Animais , Ratos , Tioacetamida/toxicidade , Resveratrol/farmacologia , Cirrose Hepática/tratamento farmacológico , Metformina/farmacologia , Imuno-Histoquímica , Citocinas/antagonistas & inibidores , Fator de Necrose Tumoral alfa , Inibidor Tecidual de Metaloproteinase-1 , Sirolimo , Serina-Treonina Quinases TOR , Inflamação , Fígado/efeitos dos fármacos , Cirrose Hepática/induzido quimicamenteRESUMO
SUMMARY: The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.
Son bien conocidosos los efectos tóxicos de la tioacetamida (TAA) y el tetracloruro de carbono en el cuerpo humano. En este estudio, examinamos si la intoxicación por TAA puede inducir la infiltración de leucocitos renales (medida como antígeno leucocitario común CD45) asociada con el aumento de las especies reactivas de oxígeno (ROS)/factor de necrosis tumoral-alfa (TNF-α), así como biomarcadores de daño renal con y sin tratamiento con metformina. A las ratas se les inyectó TAA (200 mg/kg; dos veces por semana durante 8 semanas) antes de sacrificarlas a las 10 semanas (grupo experimental) o se les pretrató con metformina (200 mg/kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuaron recibiendo ambos agentes hasta el final del experimento, en la semana 10 (grupo protector). Usando tinción histológica básica, métodos de inmunohistoquímica y análisis químico de la sangre, observamos una lesión profunda del tejido renal, como daño glomerular y tubular en el grupo experimental, que mejoraron sustancialmente con la metformina. La metformina también inhibió significativamente (p0,05) en la expresión renal de células de inmunotinción positivas para CD45. En conclusión, encontramos que el TAA induce la lesión renal en asociación con el aumento del eje ROS/TNF-α, independientemente de la infiltración de leucocitos, que está protegida por metformina.
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Animais , Masculino , Ratos , Tioacetamida/toxicidade , Injúria Renal Aguda/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Imuno-Histoquímica , Biomarcadores , Fator de Necrose Tumoral alfa , Espécies Reativas de Oxigênio , Antígenos Comuns de Leucócito , Injúria Renal Aguda/induzido quimicamente , InflamaçãoRESUMO
SUMMARY: Liver transplantation is the only available method to treat liver failure induced by chronic liver injury. We sought to determine whether the angiotensin-converting enzyme inhibitor, captopril, can inhibit the development of chronic liver injury induced by the hepatotoxic agent thioacetamide (TAA) in association with the suppression of inflammation (hsCRP, TNF-α, and IL-6) / hypoxia- inducible factor 1-alpha (HIF-1α) / profibrosis (TIMP-1, MMP-9, and α-SMA) axis that mediates liver injury. Therefore, the model group of rats was injected for eight weeks with 200 mg/kg TAA starting at week two. The protective group was pretreated with 150 mg/ kg captopril daily for two weeks prior to TAA injections and continued receiving both capropril and TAA agents until being humanely scrificed at week 10. We observed a substantial damage to liver tissue in the model group as demonstrated by a significant (p<0.0001) increase in blood and hepatic tissue levels of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-a (TNF-α), interleukin- 6 (L-6), HIF-1α, tissue inhibitor of metalloproteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), alpha-smooth muscle actin (α-SMA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). All these parameters were significantly (p<0.0244) protected by captopril. Also, a significant (p<0.0001) positive correlation was observed between a-SMA (profibrosis) and the serum and tissue levels of hsCRP, TNF-α, HIF-1α, TIMP-1, MMP-9, and ALT. Thus, these findings suggest that the induction of chronic liver injury by the hepatotoxic compound, TAA is associated with the upregulation of inflammation/HIF-1α/profibrosis, with captopril exhibiting beneficial hepatic pleotropic effects.
El trasplante de hígado es el único método disponible para tratar la insuficiencia hepática inducida por una lesión hepática crónica. Buscamos determinar si el inhibidor de la enzima convertidora de angiotensina, captopril, puede inhibir el desarrollo de lesión hepática crónica inducida por el agente hepatotóxico tioacetamida (TAA) en asociación con la supresión de la inflamación (hsCRP, TNF-α e IL-6) / factor inducible por hipoxia 1-alfa (HIF-1α) / profibrosis (TIMP-1, MMP-9 y α- SMA) eje que media la lesión hepática. Por lo tanto, al grupo modelo de ratas se le inyectó durante ocho semanas 200 mg/kg de TAA a partir de la semana dos. El grupo protector fue pretratado con 150 mg/kg de captopril al día durante dos semanas antes de las inyecciones de TAA y continuó recibiendo capropril y agentes TAA hasta que fue sacrificado en la semana 10. Observamos un daño sustancial en el tejido hepático en el grupo modelo, como lo demuestra un aumento significativo (p<0,0001) de los niveles en sangre y tejido hepático de proteína C reactiva de alta sensibilidad (hsCRP), factor de necrosis tumoral-α (TNF-a), interleucina-6 (L-6), HIF-1α, inhibidor tisular de metaloproteinasas-1 (TIMP-1), metaloproteinasa de matriz-9 (MMP-9), actina de músculo liso alfa (α-SMA), alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Todos estos parámetros estaban significativamente (p<0,0244) protegidos por captopril. Además, se observó una correlación positiva significativa (p<0,0001) entre α-SMA (profibrosis) y los niveles séricos y tisulares de hsCRP, TNF-α, HIF-1α, TIMP- 1, MMP-9 y ALT. Por lo tanto, estos hallazgos sugieren que la inducción de daño hepático crónico por el compuesto hepatotóxico, TAA, está asociada con la regulación al alza de la inflamación/HIF-1α/profibrosis, con captopril exhibiendo efectos pleotrópicos hepáticos beneficiosos.
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Animais , Masculino , Ratos , Tioacetamida/toxicidade , Captopril/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fibrose , Imuno-Histoquímica , Western Blotting , Actinas , Fator de Necrose Tumoral alfa , Inibidor Tecidual de Metaloproteinase-1 , Metaloproteinase 9 da Matriz , Modelos Animais de Doenças , Fator 1-alfa Nuclear de Hepatócito , Reação em Cadeia da Polimerase em Tempo Real , Inibidores de Metaloproteinases de Matriz , Inflamação , Fígado/efeitos dos fármacosRESUMO
The antioxidant effect of caffeine, associated with its ability to upregulate the nuclear factor-E2-related factor-2 (Nrf2)-signaling pathway, was explored as a possible mechanism for the attenuation of liver damage. Nonalcoholic steatohepatitis (NASH) was induced in rats by the administration of a high-fat, high-sucrose, high-cholesterol diet (HFSCD) for 15 weeks. Liver damage was induced in rats by intraperitoneal administration of thioacetamide (TAA) for six weeks. Caffeine was administered orally at a daily dose of 50 mg/kg body weight during the period of NASH induction to evaluate its ability to prevent disease development. Meanwhile, rats received TAA for three weeks, after which 50 mg/kg caffeine was administered daily for three weeks with TAA to evaluate its capacity to interfere with the progression of hepatic injury. HFSCD administration induced hepatic steatosis, decreased Nrf2 levels, increased oxidative stress, induced the activation of nuclear factor-κB (NF-κB), and elevated proinflammatory cytokine levels, leading to hepatic damage. TAA administration produced similar effects, excluding steatosis. Caffeine increased Nrf2 levels; attenuated oxidative stress markers, including malondialdehyde and 4-hydroxynonenal; restored normal, reduced glutathione levels; and reduced NF-κB activation, inflammatory cytokine levels, and damage. Our findings suggest that caffeine may be useful in the treatment of human liver diseases.
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Antioxidantes , Hepatopatia Gordurosa não Alcoólica , Humanos , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Tioacetamida/toxicidade , Cafeína/farmacologia , Cafeína/uso terapêutico , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fígado , Estresse Oxidativo , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), which compose the classical pathway of the renin-angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as promising therapeutic targets in neuropsychiatric disorders, leading to neuroprotection. OBJECTIVE: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice. METHODS: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. The student's t-test was applied for statistical analysis. RESULTS: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus compared with controls. CONCLUSION: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.
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Encefalopatia Hepática , Fármacos Neuroprotetores , Camundongos , Animais , Renina , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Enzima de Conversão de Angiotensina 2 , Fator de Crescimento Neural/metabolismo , Doenças Neuroinflamatórias , Interleucina-6/metabolismo , Peptidil Dipeptidase A/metabolismo , Angiotensina II/metabolismo , Fragmentos de Peptídeos/metabolismo , Tioacetamida , Hipocampo/metabolismo , Lobo Frontal/metabolismoRESUMO
INTRODUCTION AND OBJECTIVES: Caffeine consumption is associated with beneficial effects on hepatic disorders. The objectives of this study were to evaluate the antifibrotic effects of caffeine on experimental nonalcoholic steatohepatitis (NASH) induced with a high-fat, high-sucrose, high-cholesterol diet (HFSCD), as well as to evaluate the ability of caffeine to prevent the progression of experimental liver fibrosis induced by the administration of thioacetamide (TAA) in rats and explore the mechanisms of action. METHODS: NASH and fibrosis were induced in rats by the administration of an HFSCD for 15 weeks, and liver fibrosis was induced by intraperitoneal administration of 200 mg/kg TAA 3 times per week, for 6 weeks. Caffeine was administered at a dose of 50 mg/kg body weight. The effects of diet, TAA, and caffeine on fibrosis were evaluated by biochemical and histological examinations. The profibrotic pathways were analyzed by western blotting and immunohistochemistry. RESULTS: Rats exhibited liver fibrosis after HFSCD feeding and the administration of TAA. Caffeine could reduce the hepatic level of collagen and the fibrotic area in the liver. Caffeine prevented the progression of liver fibrosis by decreasing transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (α-SMA) expression and by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and Smad3 phosphorylation. CONCLUSIONS: Caffeine attenuates NASH and the progression of liver fibrosis due to its antifibrotic effects and modulating the MAPK and TGF-ß pathways. Therefore, caffeine could be a suitable candidate for treating liver diseases associated with fibrosis.
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Hepatopatia Gordurosa não Alcoólica , Tioacetamida , Animais , Cafeína/efeitos adversos , Cafeína/metabolismo , Fibrose , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ratos , Transdução de Sinais , Proteína Smad3/metabolismo , Tioacetamida/efeitos adversos , Tioacetamida/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.
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Adenoma de Células Hepáticas/prevenção & controle , Carcinoma Hepatocelular/prevenção & controle , Suplementos Nutricionais , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Vitamina D/administração & dosagem , Adenoma de Células Hepáticas/induzido quimicamente , Adenoma de Células Hepáticas/metabolismo , Adenoma de Células Hepáticas/patologia , Alanina Transaminase/sangue , Alanina Transaminase/genética , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Catalase/sangue , Catalase/genética , Quimioprevenção/métodos , Colágeno/genética , Colágeno/metabolismo , Dietilnitrosamina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Queratinas/genética , Queratinas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ratos , Ratos Wistar , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Tioacetamida/toxicidade , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. Graphical Abstract Exercise training attenuated liver injury as well as cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment.
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Cardiomiopatias/prevenção & controle , Terapia por Exercício , Cirrose Hepática/terapia , Condicionamento Físico Humano , Animais , Função do Átrio Esquerdo , Biomarcadores/sangue , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Tolerância ao Exercício , Humanos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Miocárdio/patologia , Ratos Wistar , Tioacetamida , Função Ventricular EsquerdaRESUMO
AIMS: Liver cirrhosis is the main chronic liver disease and is considered a catabolic disease. Cirrhotic patients have a low energy intake and high energy expenditure at rest, leading to metabolic disorders. Malnutrition is associated with complications of cirrhosis and has been shown that a nutritional intervention with increase of energy intake improves the survival of cirrhotic patients. Therefore, our aim was to evaluate the effect of a high sucrose diet in the liver of animals with cirrhosis induced by thioacetamide and investigate the mechanism involved. MAIN METHODS: Male Wistar rats were divided into three groups: Control; Thioacetamide; and Thioacetamide + high sucrose diet. The thioacetamide was administrated (100 mg kg-1) intraperitoneally and the sucrose was offered in drinking water (300 g L-1). KEY FINDINGS: The administration of thioacetamide was associated with fibrosis and inflammatory infiltrate in the liver and increased levels of transaminases enzymes. The high sucrose diet promoted a reduction of theses parameters in cirrhotic rats. The malnutrition observed in cirrhotic rats was attenuated by the high sucrose diet shown by the improvements in weight loss, subcutaneous fat, and caloric intake. The high sucrose diet also attenuated the oxidative stress present in the liver of animals with thioacetamide-induced cirrhosis. SIGNIFICANCE: The high sucrose diet had anti-inflammatory and anti-oxidant effects in the liver of animals with thioacetamide-induced cirrhosis. In addition, the high sucrose diet also improved malnutrition and catabolism present in cirrhosis. Thus, a high sucrose diet may be a therapeutic option for cirrhotic patients in a catabolic state.