Reversible model of magnesium depletion induced by systemic kainic acid injection in magnesium-deficient rats: I--Comparative study of various magnesium salts.
We developed three models of reversible magnesium depletion in rats resulting from the combined effects of kainic (KA) acid with magnesium deficiency, in order to compare the effects of various common magnesium salts (pidolate, aspartate, lactate, gluconate and chloride) and of magnesium acetyl taurinate (MgATa), administered daily (14 mg Mg2+, PO) for ten days. First, the immediate effects (wet dog shakes, clonic convulsions and death 1 h after injection) and late effects (fall from hole board between the second and tenth days post injection) of kainic acid at three different doses (3.6 and 11 mg/kg) were studied in magnesium deficient rats (50 ppm for 40 days) and in non-deficient rats (1700 ppm). The results showed that the effects of kainic acid were enhanced in magnesium deficient rats. Secondly, after ten days of physiological then pharmacological doses of magnesium, used as chronical supplementation, we showed that kainic acid administration combined with magnesium deficiency led to magnesium depletion of increasing severity depending on the dose of kainic acid. The observed magnesium depletions were weak at a dose of 3 mg/kg KA, moderate at a dose of 6 mg/kg and severe at a dose of 11 mg/kg. These depletions were more or less reversible, and this enabled the classification of the therapeutic effects of these salts on Mg depletion. Among common salts, magnesium pidolate presented the greatest efficacy but none of them fully prevented depletion. In contrast, MgATa was efficient on all the aspects of depletion, when administered preventively both chronically or acutely or as a single curative injection. Consequently the results we obtained in the present study, on a new model of magnesium depletion, showed the greatest efficacy of magnesium acetyl taurinate we demonstrated yet on other models of reversible magnesium depletion.
Bac
P
P
Laboratoire de: Pharmacologie, Faculté de Pharmacie, Chàtenay Malabry, France.
Herrenknecht
C
C
Pagès
N
N
Dupont
C
C
Durlach
J
J
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005527:Food, Fortified; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology; D008275:Magnesium Deficiency / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology
C083076:acetyltaurine; D013654:Taurine; D008274:Magnesium; D007608:Kainic Acid