Pregnant rats were treated orally with aluminum lactate (400 mg Al/kg/day) during three periods of gestation to determine the treatment's influence on mortality, weight gain, neuromotor maturation, and learning abilities of their pups. No effect of treatment on litter size, mortality rate, and weight gain of pups was detected. In the negative geotaxis test, the scores of pups from females treated during the second and third weeks of gestation were diminished. In the locomotor coordination and the operant conditioning tests, significant differences in the comparison of controls vs. the three treated groups were found, indicating long-term effects of early intoxication upon the central nervous system.
The effects of intraperitoneal administration of fluoxetine (2.5, 5, 10 or 20 mg kg(-1)) and norfluoxetine (10 mg kg(-1)) on 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) metabolism were examined in the blood platelets and brain of rats killed 3 h after a single dose. Several experiments were performed to evaluate the effect of norfluoxetine. Plasma 5-HT concentrations decreased significantly (48%) compared with control group results 3 h after administration of a single dose of fluoxetine (10 or 20 mg kg(-1)). Similar plasma 5-HT levels, 0.54+/-0.04 and 0.56+/-0.09 mg L(-1), respectively, were observed after administration of 10 mg kg(-1) fluoxetine or norfluoxetine. In the same way 5-HIAA levels in whole brain were similar, 0.36+/-0.03 and 0.34+/-0.01 microg(-1), respectively, after administration of fluoxetine or norfluoxetine. There was a good correlation between plasma and brain levels of fluoxetine (0.962) and norfluoxetine (0.957). The results suggest that fluoxetine and norfluoxetine lead to reduced levels of 5-HT in platelets and of 5-HIAA in the brain. Like the parent drug, norfluoxetine is a potent and selective inhibitor of 5-HT uptake.
The oral treatment of pregnant rats by aluminum chloride or lactate at various doses was applied from day 1 to day 21 of gestation to determine its influence on mortality, weight evolution, and neuromotor maturation of their pups. No effect of treatment on litter size was detected, but an increased mortality appeared during the first week: treatment by aluminum lactate was less active than was an equivalent treatment by aluminum chloride. Weight was transitorily delayed, but the reversal of this effect could be attributed to the decrease of litter size. The neuromotor maturation of surviving pups treated with the two aluminum salts showed an important impairment during the first 2 weeks of postnatal life.
According to our results, the traditional therapeutic indications of Eupatorium cannabinum L., choleretic and hepatoprotective effects, have been widely demonstrated. An aqueous extract induces hypercholeresis in the rat, the site of bile formation is canalicular in origin and both bile acid-dependent and bile acid-independent flows could be stimulated; the extract possesses anti-necrotic properties against carbon tetrachloride-induced hepatotoxicity, reducing widely the plasma GPT level in pretreated rats.
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