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Depression is a common disease that may cause severe damage to human health. Imipramine (IMI) and desipramine (DES) are medicaments used for treatment, yet studies on their genotoxic potential have given controversial results. Therefore, we designed the present assay to determine their effect as inducers of micronucleated polychromatic erythrocytes (MNPE) and micronucleated normochromatic erythrocytes (MNNE) in mice. The study was carried out in animals administered daily with the compounds for 4 weeks, and the determination of micronuclei was done each week. We also evaluated the bone marrow cytotoxicity induced by the chemicals. Besides, the same determinations were carried out in the following 4 consecutive weeks, but in this period the animals were not treated with the tested compounds. Our results showed a significant increase in both MNPE and MNNE induced by both compounds from the first week of administration. At the fourth week, IMI increased three times the control level, while the effect of DES was about seven times such level. In the second, 4-week phase, we observed a reduction in the rate of micronuclei approaching the control level. We also detected a bone marrow-mitotic division decrease by the evaluated chemicals. Our results point to the need for cautiousness in the clinical use of the compounds as well as for testing the effect in patients under treatment. Depression is a common disorder which may affect 1 out of 10 individuals during their lifetime , giving rise to serious health and socioeconomic problems [1,2]. The disease can be caused by various endogenous and exogenous factors, and it is characterized by irritability, insomnia, fatigue, psychomotor and concentration alterations in addition to a suicidal tendency [3]. The extent of clinical damage as well as its socioeconomic importance has favoured the use of a number of drugs such as the tricyclic antidepressants which are agents that, besides acting against depression, have shown pharmacological effects in the treatment of enuresis, anxiety, bulimia, anorexia, alcoholism, attention-deficit hyperactive disorder and neuralgia [3-5]. Tricyclic drugs are secondary or tertiary amines with a common core consisting of two aromatic rings fused with a seven-atom ring which may include a nitrogen heteroatom. Imipramine (IMI) is a tertiary amine that is readily demeth-ylated in vivo to the corresponding secondary amine, desipramine (DES), which is also pharmacologically active [6] (fig. 1). These two medicaments have been used for more than 40 years, and, thus, their therapeutic efficacy and secondary effects are well known. With respect to the genotoxic potential of IMI, several in vitro studies have been published as have a few others using in vivo models [1,7-12]. The authors have evaluated genetic, chromosomal and DNA breaking parameters and they have reported controversial results. In regard to DES, a conclusion about its genotoxicity is even more difficult because studies on the matter have been far more limited [1]. In a previous report, we...

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We evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

AIMTo examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats.METHODSWistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy.RESULTSIn all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganizationCONCLUSIONThe results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.