This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches.
The aim of this study was to evaluate the effects of different carotenoids sources in tilapia fish diets on the animals' performance and fillets characteristics. Nine hundred and sixty tilapias, Oreochromis niloticus, averaging 15 g were distributed into 24 tanks to receive one of the six treatments (four repetitions) for 80 days: basal diet with no pigment (control group), basal diet with 350 mg/kg astaxanthin 10 % and basal diets added of four different concentrations of Rubrivivax gelatinosus biomass (175, 350, 700 and 1400 mg/kg). Variables analyzed included feed consumption, weight gain, feed conversion and specific growth rate for the animals and pH, proximate composition, carotenoids, polyunsaturated fatty acids and color for the fillets. Productive parameters did not differ statistically. Moisture content was lower on the fillets of treatments with pigments. The protein contents on the fillets of diets supplemented with the bacterial biomass were higher than in control group, while pH, minerals and lipids did not vary among treatments. Lightness and yellowness did not differ among the treatments, but redness and carotenoids contents were higher for all the groups that received the pigments than for the control group. The ratio of polyunsaturated fatty acids n-6/n-3 was improved with the dietary biomass. So, it was concluded that the use of the pigmenting ingredients did not alter productive parameters but increased redness and carotenoids contents in the fillets. Moreover, the use of R. gelatinosus biomass also increased the protein contents and improved the fatty acids profile in the fillets.
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