Comparative histological examination of both liver and the supra-aortic arteries have not previou... more Comparative histological examination of both liver and the supra-aortic arteries have not previously examined the consequences of atherosclerosis and nonalcoholic fatty liver disease (NAFLD), and their response to diet and atorvastatin therapy. This study evaluates the effects of diet alone or in combination with atorvastatin therapy on the progression/regression of atherosclerosis and its correlation with NAFLD. This research was performed on a cohort of chickens on standard (SD) or hyperlipidemic diets (HD), either with or without atorvastatin therapy. The development of atherosclerotic lesions was assessed by histology, immunohistochemistry and quantitative image analysis and correlated with liver histology. The lowest levels of atherosclerotic lesions were found in animals on the HD for 3 months, followed by 3 months of SD in combination with oral atorvastatin. There was a strong association between the histologic findings of atherosclerosis and those of NAFLD. These studies show that standard diet and atorvastatin therapy can positively affect both arterial and hepatic lesions, influencing the regression of the changes. These results support the hypothesis that NAFLD and atherosclerosis may be actually two aspects of a shared disease and suggest the possibility of regression of both disorders with dietary and pharmacologic manipulations.
Clínica e Investigación en Arteriosclerosis, Oct 1, 2007
ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive... more ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive kidney disease. However, information on the role of statins on kidney disease in humans and animal models is lacking. Objectives To analyze the effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model using histological analysis. Material and method We used 100 White-Leghorn chickens fed with a hyperlipemic diet (induction stage), followed by an interventional stage, in which the animals were fed a normal or hyperlipemic diet and administered atorvastatin or placebo. Assessment of renal lipid accumulation was made by histologic and imaging analyses. Results In the healthy control group, no intracellular renal fat deposits or accumulations were found. The atherogenic group showed substantial lipid accumulations. The intervention group with suspension of the hyperlipemic diet and atorvastatin administration showed significant differences with the remaining groups, presenting the lowest fat accumulation. This group also showed significantly lower fat accumulation diameter with respect to the remaining groups. Conclusions Our experimental model was useful and suitable for the study of renal fat accumulation. Hyperlipemic diet suspension and simultaneous atorvastatin therapy led to the lowest renal fat accumulation. Hyperlipemic diet suspension alone produced less pronounced results. The parameters studied indicate that atorvastatin was effective in accelerating regression of renal fat accumulation and in decreasing its progression.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits and inflammatory infiltration. Statistically significant increases were observed in all plasma lipid parameters, liver macroscopic features, fat deposits and cell-ballooning of hepatocytes between control and hyperlipidemic animals. Significant differences were also observed in the inflammatory infiltration parameters (number of foci, density, area and maximal diameter). Results show that diet-induced hypercholesterolemia and hypertriglyceridemia are associated with severe impairment of liver histology (fat accumulation, inflammation and cell-ballooning), reproducing histological features of human NAFLD. This model, which is easy and reproducible, offers economic and technical advantages. Furthermore, the reversibility of the pathologic changes makes it suitable for drug intervention studies of steatohepatitis.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.
Abstract The features and pedagogical foundations of self-learning methodology in simulated envir... more Abstract The features and pedagogical foundations of self-learning methodology in simulated environments (MAES) are discussed in this article. MAES has six elements (team selection and creation of group identity, voluntary choice of subject of study, establishment of baseline and programming skills to be acquired through brainstorming, design of a clinical simulation scenario in which the students practice the skills to be acquired, execution of the simulated clinical experience, and finally debriefing and presentation of the acquired skills) that develop sequentially to achieve a high level of skills acquisition by students working in teams. The students direct their learning, design simulation scenarios, and discuss the outcomes and related scientific evidence under the guidance of a facilitator.
Comparative histological examination of both liver and the supra-aortic arteries have not previou... more Comparative histological examination of both liver and the supra-aortic arteries have not previously examined the consequences of atherosclerosis and nonalcoholic fatty liver disease (NAFLD), and their response to diet and atorvastatin therapy. This study evaluates the effects of diet alone or in combination with atorvastatin therapy on the progression/regression of atherosclerosis and its correlation with NAFLD. This research was performed on a cohort of chickens on standard (SD) or hyperlipidemic diets (HD), either with or without atorvastatin therapy. The development of atherosclerotic lesions was assessed by histology, immunohistochemistry and quantitative image analysis and correlated with liver histology. The lowest levels of atherosclerotic lesions were found in animals on the HD for 3 months, followed by 3 months of SD in combination with oral atorvastatin. There was a strong association between the histologic findings of atherosclerosis and those of NAFLD. These studies sho...
Complex interrelationships exist between hyperlipidemia and the progression of renal injury. The ... more Complex interrelationships exist between hyperlipidemia and the progression of renal injury. The aim of this study was to evaluate the impact of high plasma cholesterol and triglyceride levels on renal structure and the effects of atorvastatin on progression-regression of renal injury. One-hundred chickens were divided into five groups: Group A: Standard diet (SD) for 6 months; Group B: Hyperlipidemic diet (HD) for 6 months; Group C: HD for three months and SD during the next 3 months; Group D: HD for 3 months and SD during the next 3 months, when they received oral atorvastatin (3 mg/kg/d); Group E: HD for the whole 6 months, and atorvastatin (3 mg/kg/d) during the last 3 months. Increased alpha-actine immunostaining was found in glomeruli of groups B and C. An important decrease of immunostaining was observed in glomeruli of atorvastatin treated groups. Group D showed the lowest value for presence of lipids, and significant differences were found with respect to the rest of the gr...
Introduccion La enfermedad grasa del higado no alcoholica (EGHNA) se asocia a patologia vascular ... more Introduccion La enfermedad grasa del higado no alcoholica (EGHNA) se asocia a patologia vascular subsidiaria de ser tratada con estatinas, por ello creemos de interes desarrollar un modelo de esteatosis hepatica en animales y valorar el efecto de la atorvastatina en la lesion hepatica inducida, asi como presentar metodos de evaluacion macroscopica y microscopica de los grados de esteatosis. Metodos Se emplearon pollos de la raza White- Leghorn, clasificados en 5 grupos experimentales con diferentes dietas y tratamiento con atorvastatina. Los higados fueron valorados y clasificados macroscopica y microscopicamente en 4 grados de lesion. Resultados En el presente trabajo se ha conseguido desarrollar un modelo de higado graso inducido por una dieta aterogenica empleando el pollo como animal de experimentacion. Conclusion Se demuestra que este modelo es adecuado para el estudio de la esteatosis hepatica. Ademas, se muestran dos metodos de valoracion de los grados de lesion: macroscopico y microscopico. Se concluye que la valoracion macroscopica es util para una discriminacion rapida del efecto de la dieta, observandose tambien una tendencia al efecto beneficioso de la atorvastatina aunque no sea estadisticamente significativa. La evaluacion microscopica, basada en los depositos lipidicos, completa este estudio dando un mayor detalle de los grados de lesion, especialmente en los grados de lesion intermedios. Por este analisis microscopico se demuestra una reduccion de la lesion hepatica en los grupos tratados con atorvastatina. La combinacion de los dos metodos, macroscopico y microscopico, es de gran utilidad para las valoraciones de los grados de lesion de esteatosis hepatica.
ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive... more ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive kidney disease. However, information on the role of statins on kidney disease in humans and animal models is lacking. Objectives To analyze the effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model using histological analysis. Material and method We used 100 White-Leghorn chickens fed with a hyperlipemic diet (induction stage), followed by an interventional stage, in which the animals were fed a normal or hyperlipemic diet and administered atorvastatin or placebo. Assessment of renal lipid accumulation was made by histologic and imaging analyses. Results In the healthy control group, no intracellular renal fat deposits or accumulations were found. The atherogenic group showed substantial lipid accumulations. The intervention group with suspension of the hyperlipemic diet and atorvastatin administration showed significant differences with the remaining groups, presenting the lowest fat accumulation. This group also showed significantly lower fat accumulation diameter with respect to the remaining groups. Conclusions Our experimental model was useful and suitable for the study of renal fat accumulation. Hyperlipemic diet suspension and simultaneous atorvastatin therapy led to the lowest renal fat accumulation. Hyperlipemic diet suspension alone produced less pronounced results. The parameters studied indicate that atorvastatin was effective in accelerating regression of renal fat accumulation and in decreasing its progression.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits...
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.
Comparative histological examination of both liver and the supra-aortic arteries have not previou... more Comparative histological examination of both liver and the supra-aortic arteries have not previously examined the consequences of atherosclerosis and nonalcoholic fatty liver disease (NAFLD), and their response to diet and atorvastatin therapy. This study evaluates the effects of diet alone or in combination with atorvastatin therapy on the progression/regression of atherosclerosis and its correlation with NAFLD. This research was performed on a cohort of chickens on standard (SD) or hyperlipidemic diets (HD), either with or without atorvastatin therapy. The development of atherosclerotic lesions was assessed by histology, immunohistochemistry and quantitative image analysis and correlated with liver histology. The lowest levels of atherosclerotic lesions were found in animals on the HD for 3 months, followed by 3 months of SD in combination with oral atorvastatin. There was a strong association between the histologic findings of atherosclerosis and those of NAFLD. These studies show that standard diet and atorvastatin therapy can positively affect both arterial and hepatic lesions, influencing the regression of the changes. These results support the hypothesis that NAFLD and atherosclerosis may be actually two aspects of a shared disease and suggest the possibility of regression of both disorders with dietary and pharmacologic manipulations.
Clínica e Investigación en Arteriosclerosis, Oct 1, 2007
ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive... more ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive kidney disease. However, information on the role of statins on kidney disease in humans and animal models is lacking. Objectives To analyze the effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model using histological analysis. Material and method We used 100 White-Leghorn chickens fed with a hyperlipemic diet (induction stage), followed by an interventional stage, in which the animals were fed a normal or hyperlipemic diet and administered atorvastatin or placebo. Assessment of renal lipid accumulation was made by histologic and imaging analyses. Results In the healthy control group, no intracellular renal fat deposits or accumulations were found. The atherogenic group showed substantial lipid accumulations. The intervention group with suspension of the hyperlipemic diet and atorvastatin administration showed significant differences with the remaining groups, presenting the lowest fat accumulation. This group also showed significantly lower fat accumulation diameter with respect to the remaining groups. Conclusions Our experimental model was useful and suitable for the study of renal fat accumulation. Hyperlipemic diet suspension and simultaneous atorvastatin therapy led to the lowest renal fat accumulation. Hyperlipemic diet suspension alone produced less pronounced results. The parameters studied indicate that atorvastatin was effective in accelerating regression of renal fat accumulation and in decreasing its progression.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits and inflammatory infiltration. Statistically significant increases were observed in all plasma lipid parameters, liver macroscopic features, fat deposits and cell-ballooning of hepatocytes between control and hyperlipidemic animals. Significant differences were also observed in the inflammatory infiltration parameters (number of foci, density, area and maximal diameter). Results show that diet-induced hypercholesterolemia and hypertriglyceridemia are associated with severe impairment of liver histology (fat accumulation, inflammation and cell-ballooning), reproducing histological features of human NAFLD. This model, which is easy and reproducible, offers economic and technical advantages. Furthermore, the reversibility of the pathologic changes makes it suitable for drug intervention studies of steatohepatitis.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.
Abstract The features and pedagogical foundations of self-learning methodology in simulated envir... more Abstract The features and pedagogical foundations of self-learning methodology in simulated environments (MAES) are discussed in this article. MAES has six elements (team selection and creation of group identity, voluntary choice of subject of study, establishment of baseline and programming skills to be acquired through brainstorming, design of a clinical simulation scenario in which the students practice the skills to be acquired, execution of the simulated clinical experience, and finally debriefing and presentation of the acquired skills) that develop sequentially to achieve a high level of skills acquisition by students working in teams. The students direct their learning, design simulation scenarios, and discuss the outcomes and related scientific evidence under the guidance of a facilitator.
Comparative histological examination of both liver and the supra-aortic arteries have not previou... more Comparative histological examination of both liver and the supra-aortic arteries have not previously examined the consequences of atherosclerosis and nonalcoholic fatty liver disease (NAFLD), and their response to diet and atorvastatin therapy. This study evaluates the effects of diet alone or in combination with atorvastatin therapy on the progression/regression of atherosclerosis and its correlation with NAFLD. This research was performed on a cohort of chickens on standard (SD) or hyperlipidemic diets (HD), either with or without atorvastatin therapy. The development of atherosclerotic lesions was assessed by histology, immunohistochemistry and quantitative image analysis and correlated with liver histology. The lowest levels of atherosclerotic lesions were found in animals on the HD for 3 months, followed by 3 months of SD in combination with oral atorvastatin. There was a strong association between the histologic findings of atherosclerosis and those of NAFLD. These studies sho...
Complex interrelationships exist between hyperlipidemia and the progression of renal injury. The ... more Complex interrelationships exist between hyperlipidemia and the progression of renal injury. The aim of this study was to evaluate the impact of high plasma cholesterol and triglyceride levels on renal structure and the effects of atorvastatin on progression-regression of renal injury. One-hundred chickens were divided into five groups: Group A: Standard diet (SD) for 6 months; Group B: Hyperlipidemic diet (HD) for 6 months; Group C: HD for three months and SD during the next 3 months; Group D: HD for 3 months and SD during the next 3 months, when they received oral atorvastatin (3 mg/kg/d); Group E: HD for the whole 6 months, and atorvastatin (3 mg/kg/d) during the last 3 months. Increased alpha-actine immunostaining was found in glomeruli of groups B and C. An important decrease of immunostaining was observed in glomeruli of atorvastatin treated groups. Group D showed the lowest value for presence of lipids, and significant differences were found with respect to the rest of the gr...
Introduccion La enfermedad grasa del higado no alcoholica (EGHNA) se asocia a patologia vascular ... more Introduccion La enfermedad grasa del higado no alcoholica (EGHNA) se asocia a patologia vascular subsidiaria de ser tratada con estatinas, por ello creemos de interes desarrollar un modelo de esteatosis hepatica en animales y valorar el efecto de la atorvastatina en la lesion hepatica inducida, asi como presentar metodos de evaluacion macroscopica y microscopica de los grados de esteatosis. Metodos Se emplearon pollos de la raza White- Leghorn, clasificados en 5 grupos experimentales con diferentes dietas y tratamiento con atorvastatina. Los higados fueron valorados y clasificados macroscopica y microscopicamente en 4 grados de lesion. Resultados En el presente trabajo se ha conseguido desarrollar un modelo de higado graso inducido por una dieta aterogenica empleando el pollo como animal de experimentacion. Conclusion Se demuestra que este modelo es adecuado para el estudio de la esteatosis hepatica. Ademas, se muestran dos metodos de valoracion de los grados de lesion: macroscopico y microscopico. Se concluye que la valoracion macroscopica es util para una discriminacion rapida del efecto de la dieta, observandose tambien una tendencia al efecto beneficioso de la atorvastatina aunque no sea estadisticamente significativa. La evaluacion microscopica, basada en los depositos lipidicos, completa este estudio dando un mayor detalle de los grados de lesion, especialmente en los grados de lesion intermedios. Por este analisis microscopico se demuestra una reduccion de la lesion hepatica en los grupos tratados con atorvastatina. La combinacion de los dos metodos, macroscopico y microscopico, es de gran utilidad para las valoraciones de los grados de lesion de esteatosis hepatica.
ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive... more ABSTRACT Introduction There is evidence of a relationship between atherosclerosis and progressive kidney disease. However, information on the role of statins on kidney disease in humans and animal models is lacking. Objectives To analyze the effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model using histological analysis. Material and method We used 100 White-Leghorn chickens fed with a hyperlipemic diet (induction stage), followed by an interventional stage, in which the animals were fed a normal or hyperlipemic diet and administered atorvastatin or placebo. Assessment of renal lipid accumulation was made by histologic and imaging analyses. Results In the healthy control group, no intracellular renal fat deposits or accumulations were found. The atherogenic group showed substantial lipid accumulations. The intervention group with suspension of the hyperlipemic diet and atorvastatin administration showed significant differences with the remaining groups, presenting the lowest fat accumulation. This group also showed significantly lower fat accumulation diameter with respect to the remaining groups. Conclusions Our experimental model was useful and suitable for the study of renal fat accumulation. Hyperlipemic diet suspension and simultaneous atorvastatin therapy led to the lowest renal fat accumulation. Hyperlipemic diet suspension alone produced less pronounced results. The parameters studied indicate that atorvastatin was effective in accelerating regression of renal fat accumulation and in decreasing its progression.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits...
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease... more Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.
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