ABSTRACT
PURPOSE: Nonalcoholic steatohepatitis (NASH) has been associated with irinotecan (IRI)-based cancer chemotherapy regimens. The purpose of this study was to propose and test a consistent model of IRI-induced NASH, filling a gap in the medical literature. METHODS: Swiss male mice were distributed in groups (n = 8) and injected with saline (5 mL/kg, i.p.; control) or IRI (25, 50, 75 or 100 mg/kg, i.p.) thrice a week for 7 weeks. Blood samples were collected to measure the serum concentrations of proteins, alanine and aspartate aminotransferases (ALT and AST). Each week animals were euthanized, and the livers were submitted to myeloperoxidase (MPO) assay, lipid dosage, immunohistochemistry for inducible nitric oxide synthase (iNOS), TNF-α and interleukin-1ß (IL-1ß), and histopathological analysis. Survival rates were also determined. RESULTS: Mice treated with IRI had a significantly (p < 0.05) lower survival rate than controls and time- and dose-dependent body weight loss. ALT and AST plasma levels increased in relation to controls only in mice receiving IRI 50 mg/kg (p < 0.05). The histopathological features characteristic of NASH was observed, including steatosis, lobular neutrophil infiltration and ballooning hepatocytic degeneration. Additional findings included increased MPO, lipid accumulation, portal neutrophil infiltration, IL-1ß and iNOS expression and fibrosis in liver tissues and low serum protein levels compared to controls. CONCLUSION: This is the first report of a consistent model of IRI-induced NASH capable of mimicking clinical findings.
Subject(s)
Camptothecin/analogs & derivatives , Fatty Liver , Liver , Mice , Alanine Transaminase/blood , Animals , Antineoplastic Agents, Phytogenic/metabolism , Aspartate Aminotransferases/blood , Camptothecin/metabolism , Camptothecin/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Fatty Liver/chemically induced , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/physiopathology , Humans , Interleukin-1beta/metabolism , Irinotecan , Liver/metabolism , Liver/pathology , Male , Peroxidase/metabolism , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Weight Loss/drug effectsABSTRACT
Este trabalho tem por objetivo analisar as principais contribuições de epistemólogos sobre as concepções de normal e patológico, saúde e doença, e fazer uma apreciação desses conceitos diante dos avanços tecnológicos da medicina. Discute em especial o conflito ético da conduta cirúrgica do médico oftalmologista, quando extrai o cristalino normal (segundo os pressupostos de normalidade referidos por esses autores) e implanta, em seu lugar, uma lente artificial, que acrescenta à visão do paciente, portador de ametropia ou presbiopia, qualidades superiores as com cristalino normal. Além disso, o autor faz um exercício de previsão das possíveis alterações nos conceitos de normal e patológico, nas pessoas sem implantes e com implantes. Conclui por considerar que o acréscimo de qualidades visuais em grande parte da população poderá modificar o conceito de normal e patológico, tornando deficiente a parcela da população que não tem acesso a essas novas tecnologias.
Este trabajo tiene como objetivo analizar las principales aportaciones de los epistemólogos sobre las concepciones de lo que es normal y lo que es patológico, salud y enfermedad, y hacer una apreciación de dichos conceptos frente a los avances tecnológicos de la medicina. Discuteespecialmente el conflicto ético de la conducta quirúrgica del médico oftalmólogo, cuando extrae el cristalino normal (según las presuposiciones de normalidad referidos por esos autores) e implanta, en su lugar, una lente artificial, que acrecienta a la visión del paciente, portador de Ametropía o Presbicia, capacidades superiores a las del cristalino normal. Además de eso, el autor hace un ejercicio de previsión de las posibles alteraciones en los conceptos de normal y patológico,en las personas con y sin implantes. Concluye considerando que el incremento de capacidades visuales en gran parte de la población podrá modificar el concepto de normal y patológico, tornando deficiente a parte de la población que no tiene acceso a esas nuevas tecnologías.
The objective of this study is to investigate the main epistemological contributions on the concepts of normal and pathological, health and disease, and to analyze these concepts in face of medical technology advances. It discusses particularly about the ethical conflict of the surgicalophthalmologist conduct, when he removes the normal eye lens (according to the concept of normality reported by these authors) and implants in its place, an artificial one, adding to patient?s vision, carrier of ametropy and presbyopia, superior qualities than normal eye lens. Also, the author makes an attempt to forecast possible changes in the concepts of normal and pathological in people with and without implants. He concludes by considering the addition of visual qualities on the major portion of the population may change the concept of normal and pathological, making deficient the part of population that doesn?t have access to those new technologies.
