No abstract

The tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, was tested in a two-stage protocol of hepatocarcinogenesis in male and female Fischer 344 rats. Propranolol is a lipophilic non-selective beta-blocker mainly eliminated via the liver; atenolol is a hydrophilic beta 1-selective blocking agent, mainly eliminated via the kidney. Animals were initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and, after 17 days of recovery, were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage for up to 21 months. Rats given phenobarbital (0.05% in the diet) were used as positive controls. After 2, 4 and 8 months of promotion, preneoplastic lesions were quantified by staining sections of liver for gamma-glutamyltranspeptidase (GGT). In non-initiated rats, neither propranolol nor atenolol influenced the development of spontaneous preneoplastic or neoplastic liver lesions. The results obtained in DEN-initiated rats given propranolol cannot be unequivocally interpreted. In the male, propranolol seemed to be ineffective. In the female, there was weak enhancement of DEN-induced GGT foci at 4 and 8 months and of neoplastic lesions thereafter. However, there was great interindividual variability in focus and tumor yields. Unfortunately, due to the high incidence of liver tumors in rats given DEN alone and the small number of propranolol-treated rats that survived until the end of the experiment, no definite conclusion can be drawn about the modifying potential of this beta-blocker on liver carcinogenesis. There was no evidence of liver tumor promotion in DEN-initiated rats of either sex given atenolol.

No abstract

En el ganado vacuno, el estrés pre-sacrificio provoca la aparición de carnes conocidas como DFD (Dark, Firm, Dry), que se identifican por un descenso anómalo del pH muscular post-mortem y que muestran serios problemas de calidad, lo cual disminuye su valor comercial. El objetivo de este trabajo es conocer las diferencias en los procesos de estrés oxidativo, en los mecanismos de supervivencia/muerte celular (autofagia/apoptosis) y en biomarcadores proteómicos a las 24 h post-mortem, entre canales que mostraron un descenso normal de pH (pH = 5,4-5,8 a las 24 h post-mortem) utilizadas como CONTROL y canales con pH a las 24 h post-mortem (pH 24 ) > 6,0 clasificadas como DFD, con el fin de identificar los procesos del metabolismo muscular ligados a la aparición de carnes DFD.Se analizó el estrés oxidativo celular mediante el estudio de la actividad antioxidante total y los daños en macromoléculas (proteínas y lípidos). Las carnes DFD mostraron mayor actividad antioxidante (P < 0,05) a las 24 h post-mortem, así como mayor daño de proteínas (P < 0,05). También se analizaron biomarcadores de autofagia (Beclin-1 y LC3-II/LC3-I) y apoptosis (caspasa-3), así como los cambios producidos en el proteoma muscular. Los resultados demuestran la coexistencia de autofagia y apoptosis en el tejido muscular a las 24 h post-mortem, con diferencias de expresión significativas (P < 0,05) que permiten discriminar carnes DFD frente a carnes sin alteraciones de calidad (CONTROL).

Before incubation, chick embryos were treated with the herbicide 2,4-dichlorophenoxy acetic acid (2,4-D) by injecting onto the inner shell membrane solutions of 0, 0.5, 1, 2, or 4 mg 2,4-D. A commercial formulation containing 37% 2,4-D iso-octyl ester as active ingredient and pure 2,4-D were tested. Sister chromatid exchange (SCE) and cell cycle kinetics were examined at days 4, 7, and 10 from 22 to 30 embryos per group. After 4 days of exposure to commercial 2,4-D, a small (P < 0.05) dose-related increase of SCE was seen for the 4-mg group. An enhanced SCE response upon long-term exposure to 2,4-D was apparent. After 10 days of exposure, SCE frequencies for the 2- and 4-mg commercial 2,4-D, and 4-mg pure 2,4-D groups were significantly higher than for the controls. A significant slowing of cell cycle at concentrations at and above 1 mg was seen. Also observed was a slight, not statistically significant proliferative effect at the lowest dose of 0.5 mg/embryo. Consistent with the results from other test systems, the present findings indicate that 2,4-D has a low to moderate genotoxic activity.