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Biomedical subjects

M Salazar

Publications and source records attributed to M Salazar.

122 records · Page 7Linked to original sources

The alkaloids of Delphinium cashmirianum.

Dephinium cashmirianum Royle (Ranunculaceae) has yielded the new base cashmiradelphine (12), together with the known alkaloids anthranoyllycoctonine (9), lycaconitine (15), avadharidine (17), lappaconitine (4), and N-deacetyllappaconitine (7). Pyridinium chlorochromate oxidation of lycoctonine furnished the new aldehyde lycoctonal (11). The arrhythmogenic and heart rate effects of several of these diterpenoidal alkaloids have been measured on the isolated guinea atria. Lappaconitine was arrhythmogenic at 10(-4)M concentrations. But in contrast to the reference drug aconitine, lappaconitine did not increase the heart rate. In anesthetized rabbits injected with lappaconitine, N-deacetyllappaconitine, and lappaconine up to 1 mg/kg, cardiac arrhythmia was quickly observed. Even up to 5 mg/kg, the other substances were non-arrhythmogenic.

Alkaloids↗

Effect of neonatal administration of an antidopaminergic drug (metoclopramide) on sexual behavior of male rats.

Metoclopramide is an antidopaminergic drug that binds D2 receptor at the central nervous system and peripheral levels. Recent studies have demonstrated the presence of a sexually dimorphic nucleus in the anterior hypothalamus of rats and humans. The sexual differentiation of brain and its expression on sexual behavior is directed by catecholamines and steroids, which in turn will determine the masculinization of the preoptic area of the hypothalamus. Metoclopramide blocking dopaminergic receptor inhibits dopamine action and therefore brain masculinization. To determine the effects of the administration of this antidopaminergic drug in neonatal male rats, the design of the study considered measurements of mounts, penis intromission, and ejaculation in adult male rats treated neonatally with 100 microg metoclopramide. The administration of the drug or the vehicle (control) was by subcutaneous route during the third and fifth days of postnatal life. Six of 10 neonatally treated rats did not express male sexual activity in adulthood, while all control rats showed the characteristic pattern of male sexual behavior. Frequency of ejaculation in the rats treated with metoclopramide was 1.5 +/- 1 as compared to 5.0 +/- 0.9 in control rats (p < .01). There were meaningful differences with respect to the frequency of intromission in experimental rats (16 +/- 8) compared to control rats (115 +/- 18; p < .01). There is strong evidence that metoclopramide neonatally administered inhibits male sexual behavior in adult rats. Dopamine may be implicated in the process of neonatal brain sexual differentiation.

Animals↗

[The anti-implantation effects of various savine extracts on the pregnant rat].

Ether and ethyl acetate extracts obtained after savin essential oil extraction, were administered, on days 1 to 4, to pregnant rats by intragastric catheter, at doses of 0, 50 or 150 mg/Kg, to search for their possible effects on implantation. The ethyl acetate extract was not toxic. Inversely, the ether extract was responsible for a dose-dependent anti-implantation effect, thus showing that essential oil is not alone responsible for the abortive effect generally attributed to Savin.

Animals↗

[Pharmacology and toxicology of Guatteria gaumeri and alpha-asarone].

Guatteria gaumeri Greenman (Annonacease) has been used as bark infusion in the traditional mexican medicine for the treatment of hypercholesterolemia and cholelithiasis. The main component is alpha-asarone which has been isolated by different extraction procedures and subsequently synthetized, as well as 16 analogs, derivatives of 4-propenyl-1,2-dimethoxybenzenes 5-substituted. After daily dosing per os of 80 mg/kg of alpha-asarone and the amino and metoxi analogs for seven days to hypercholesterolemic male rats, cholesterol decreased 57.3, 37.5 and 46.9% and triglycerides diminished 42.5, 67.6 and 17.2% respectively. Some of the other analogs showed also important hypolipidemic activity. Similarly alpha-asarone decreased 80.6% the weight of gallstones in hamsters. Studies using adult rat hepatocytes suggest that at least part of the hypolipidemic effect of alpha-asarone could be due to a decrease in the secretion of lipids. Alpha-asarone did not produce any toxic effect after oral administration to rats of 10 or 50 mg/kg for 28 days, or genotoxicity by the dominant lethal test. However long-term exposure of cultivated hepatocytes to micromolar concentrations produced morphologic and ultrastructural alterations, triacylglycerol accumulation and inhibition of protein synthesis and secretion. At the same time both the Ames and sister-chromatid exchange tests showed genotoxic effect. No teratogenicity was observed in pregnant rats during organogenesis but in mice slight fetal toxicity was manifested by hydrocephaly, skeletal defects and fetal weight retardation. There are no data on the possible exposure levels in humans consuming the bark extract, but the toxic effects of alpha-asarone in animals suggest caution in the use of this plant.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

[Evaluation of the toxicity of indorenate on reproduction].

Indorenate (TR3369) a new antihypertensive drug, was examined for effects upon general reproductive performance, for peri-postnatal and embryofetal toxicity in the rat at doses of 0, 10, 20, 40 and 60 mg/kg/day by oral administration. Excluding the 60 mg/kg dose, in the fertility study, any dose produced neither decrement of body weight gain of progenitors, fertility, fetal weight nor survival rate. Retardation of the surface righting, pinnal unfolding or startle response were not observed. On the other hand, 40 and 60 mg/kg significantly increased the number of resorptions. In the peri-postnatal study, doses of 40 and 60 mg/kg incremented the number of dead pups at birth, and the later also affected the survival rate, growing and air righting reflex. Reproductive performance of the F1 offsprings was unimpaired. Indorenate in contrast to serotonin, from which it is a structural derivative, gave no evidence of teratogenicity when administered during the period of organogenesis. It was concluded that the parameters of fetal development were not affected by doses of up to 20 mg/kg, which represents approximately 1200 times the proposed dose for hypertensive patients.

5-Methoxytryptamine↗

[Pharmacology and toxicology of Spirulina alga].

Spirulina, a unicellular filamentous blue-green alga has been consumed by man since ancient times in Mexico and central Africa. It is currently grown in many countries by synthetic methods. Initially the interest in Spirulina was on its nutritive value: it was found almost equal to other plant proteins. More recently, some preclinical testing suggests it has several therapeutic properties such as hypocholesterolemic, immunological, antiviral and antimutagenic. This has led to more detailed evaluations such as nucleic acid content and presence of toxic metals, biogenic toxins and organic chemicals: they have shown absence or presence at tolerable levels according to the recommendations of international regulatory agencies. In animal experiments for acute, subchronic and chronic toxicity, reproduction, mutagenicity, and teratogenicity the algae did not cause body or organ toxicity. In all instances, the Spirulina administered to the animals were at much higher amounts than those expected for human consumption. On the other hand there is scant information of the effects of the algae in humans. This area needs more research.

Animals↗