Germán Chamorro

Acute and nongenomic effects of testosterone on isolated and perfused rat heart

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.

Effect of Spirulina maxima consumption on reproduction and peri- and postnatal development in rats

Spirulina maxima, an edible micro-organism useful in human nutrition, was examined for its effect on general reproductive performance and for peri- and postnatal toxicity in rats at levels of 0, 10, 20 and 30% (w/w) incorporated into the diet. There was no reduction in body weight gain in males or females and no deaths or clinical signs of toxicity. Treatment was not associated with any adverse effect on any measure of reproductive performance, including male and female fertility and duration of gestation. There was no increase in the number of abnormal pups at caesarean section or at birth. S. maxima consumption did not result in adverse effects on developmental markers of the pups.

Induction of sister chromatid exchanges by 2,4-dichlorophenoxyacetic acid in somatic and germ cells of mice exposed in vivo.

2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most widely used selective herbicides throughout the world; however, the studies that have been conducted to establish its genotoxic potential have given conflicting results. The aim of this investigation was to determine whether the herbicide increases the frequency of sister chromatid exchanges (SCEs) in bone marrow and spermatogonial cells of mice exposed in vivo. The experiment included an oral administration of 2,4-D to three groups of mice (50,100 and 200 mg/kg), as well as to a control group of animals administered with distilled water, pH 10.5 and another group injected with cyclophosphamide (50 mg/kg). In somatic cells, the results showed a significant SCE increase with the two high doses tested, a response that was manifested in a dose-dependent manner. With regard to the mitotic index and the cell proliferation kinetics, there were no modifications exerted by 2,4-D; however, cyclophosphamide induced cytotoxic damage and a cell-cycle delay. With respect to the germ cells, the genotoxic results were similar to those described earlier; that is, there was a significant SCE increase induced by the two high 2,4-D doses tested and a higher genotoxic damage was observed in the animals treated with cyclophosphamide. Our investigation established that 2,4-D is a moderate genotoxicant in mice treated in vivo with high doses, and suggests a minor hazard for humans in the present conditions of its use.

Synthesis and hypolipidaemic evaluation of a series of α-asarone analogues related to clofibrate in mice

A series of α‐asarone analogues related to clofibrate, containing an acetic acid group at C‐2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also synthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipoprotein cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol and triglycerides after oral administration of 40 and 80 mg kg−1 for 6 days.

Spirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

Abstract Spirulina is an alga that has a high nutritional value and some of its biological activities are attributed to the presence of antioxidants. Oxidative stress is involved in Parkinsons disease. This study aims at evaluating the neuroprotective role of Spirulina maxima (Sp.) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, used as a model of Parkinsons disease. Ninety-six male C-57 black mice were pretreated with Spirulina for 14 days (25, 50, 100, 150 or 200 mg/kg, oral), followed by three MPTP administrations (30 mg/kg, intraperitoneal, i.p.). Animals were given Sp. for 8 additional days. After the treatment, the striatal dopamine (DA) content was analysed by high performance liquid chromatography, and lipid peroxidation was studied as an index of oxidative stress. Sp. pretreatment at 150 mg/kg partially prevented (51 %) the DA-depleting effect of MPTP and blocked oxidative stress. Spirulina partially prevents MPTP neurotoxicity and oxidative stress, suggesting it could be a possible alternative in experimental therapy.

Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties

Anticonvulsant properties of α-asarone were studied in mice at three doses with different toxicity. The 100mg/kg dose decreased both treadmill performance and locomotor activity, caused hypothermia, and potentiated pentobarbital-induced sleep. The last two effects and no toxicity were observed at 60 and 22mg/kg, respectively. In chemical (pentylenetetrazole, picrotoxin, N-methyl-D-aspartate, pilocarpine) and electrical (maximal electroshock) seizure tests, neither seizures nor death were prevented by 60 mg/kg α-asarone which, however, exhibited protective-like effects (delay in the onset of clonic and/or tonic seizures and/or in the death of mice). Magnesium deficiency-dependent audiogenic seizures responded to non-toxic doses of α-asarone (60 mg/kg and less): 22 mg/kg protecting 50% of tested animals. Because these seizures respond to both anti-seizure and antioxidant compounds, antioxidant properties of α-asarone were studied, indicating 5 Units of superoxide dismutase-like activity per mg α-asarone. Treatment of mice by α-asarone (daily dose of 100mg/kg during 7 days) induced brain antioxidant enzymes (superoxide dismutase, glutathione peroxidase and reductase) in striatum and hippocampus and to a lesser extent in cortex. In view of recent findings about deleterious roles of chronic inflammatory/oxidant stresses in human epilepsy outcome, antioxidant and inductive properties of α-asarone are proposed to be coherent bases for traditional clinical efficacy.

Inhibitors of HMG-CoA Reductase: Current and Future Prospects

High levels of cholesterol are a primary risk factor in the development of cardiovascular diseases. In this review, we have summarized the structural, chemical and computational aspects of hypocholesterolemic drugs, both statins and non-statins, that target enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) to block cholesterol biosynthesis.

Anticlastogenic effect of Spirulina maxima extract on the micronuclei induced by maleic hydrazide in Tradescantia.

The aim of this investigation was to determine if extracts of Spirulina maxima reduce the genotoxic damage induced by maleic hydrazide (MH) using the Tradescantia biosssay. Two types of extracts from the alga were prepared: an aqueous extract with two different concentrations, 100 and 500 mg/ml, and a second one, the extract of a 1% solution of dimethyl sulfoxide (DMSO) which corresponded to 100 mg/ml of the alga. The capacity of MH to induce micronuclei (MN) was initially established by administering 0.005, 0.01, and 0.015 mg/ml of the chemical to the Tradescantia inflorescences, and observing its effect after 24 h.The results of this experiment showed a significant MN increase with the two high concentrations tested, although no dose-response effect was observed. For the anticlastogenic assay, the extracts of Spirulina were applied to the inflorescences alone or immediately before the application of MH (0.01 mg/ml) and the induced MN were observed 24 h later. We found that none of the extracts increased the MN level with respect to the untreated plants; also, that MH more or less doubled the basal micronuclei frequency, and finally, that all tested extracts reduced the genotoxic damage caused by MH. The inhibitory indices obtained for the aqueous extracts (100 and 500 mg/ml) and for the DMSO extract were respectively 59, 85, and 56.3%. These data indicate that Spirulina is an anticlastogenic agent and suggest that it is advisable to extend studies on this matter using other biological models.

Dominant lethal study of Spirulina maxima in male and female rats after short‐term feeding

The algae Spirulina maxima has been considered for use as a supplementary protein in feed and food, as well as an hypocholesterolaemic and antiherpes simplex virus agent. In this paper the mutagenic potential was investigated in animals of each sex. Sexually mature male or female Wistar rats, received the algae incorporated into experimental diets at levels of 0, 10%, 20% and 30%, using a short‐term (5 day) feeding, after which dominant lethal studies were conducted. The studies were carried out in two phases: a male dominant lethal phase in which untreated females cohabited for 8 weeks with treated males, two females each week, and the fetuses were evaluated 14 days after the mid‐point of the week of cohabitation; and a female dominant lethal phase in which untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation. Examination of surgically exposed uteri and ovaries of pregnant females for counting pre‐ and post‐implantation losses did not show germinal mutations, as manifested by a dominant lethal effect in males and females. In an additional study in males, no significant alterations were observed in semen counts, motility and shape of sperm. Sex organ weights failed to reveal any alteration.

Hypolipidaemic activity of dimethoxy unconjugated propenyl side‐chain analogs of α‐asarone in mice

The hypolipidaemic activity of several dimethoxy unconjugated propenyl side‐chain analogs of α‐asarone were investigated in hyperlipidaemic mice after six days of treatment. Eugenol and the α‐asarone analog with amino groups on the C‐4 position of the aromatic ring were observed to be the most effective hypolipidaemic agents at the dose of 80 mg/kg/day p.o. These compounds significantly lowered total serum cholesterol, low density lipoprotein (LDL‐cholesterol), and triglycerides content. On the other hand, high density lipoprotein (HDL‐cholesterol) was increased by administration of these hypolipidaemic agents. The ability to modulate the levels of these lipids suggests that these agents could be effective in the treatment of hyperlipidaemic states. These compounds appeared to be safe when administered at an oral dose of 80 mg/kg/day, which is within the therapeutic range in mice. Drug Dev. Res. 43:105–108, 1998.