Comparative study of the efficacy of potassium magnesium L-, D- and DL-aspartate stereoisomers in overcoming digoxin- and furosemide-induced potassium and magnesium depletions
Author(s) : Igor N Iezhitsa, Alexander A Spasov, Natalia V Zhuravleva, Maxim K Sinolitskii, Sergey P Voronin , Volgograd State Medical University, Research Institute of Pharmacology, 1 Pavshikh Bortsov Sq., Volgograd, 400131, Russia, “BioAmid”, 27 Mezhdunarodnaya St., Saratov, 410033, Russia.
Summary : Potassium and magnesium aspartate (K,Mg aspartate) is used in treating and preventing cardiac disruptions caused by electrolytic disturbances, primarily low potassium (K) and magnesium (Mg) levels (e.g. in the treatment with cardiac glycosides and diuretic drugs). Widely used, K,Mg aspartate is synthesized from aspartic acid representing a racemic mix of L- and D-stereoisomers. Differences in metabolism and utilisation of D- and L-amino acids probably have an effect on the pharmacological properties of K,Mg L- and D-aspartates, and what is more, pharmacological doses of magnesium and potassium salts may induce toxicity, which differs according to the nature of the anions. Therefore, the purpose of the present work was to study the effect of intravenously administered K,Mg L-aspartate in comparison with its D- and DL-stereoisomers on K and Mg restoration rates in plasma, erythrocytes and myocardium and to evaluate the urine excretion rate of amine nitrogen and Mg in digoxin and furosemide treated rats. To induce Mg depletion, male rats, weighing 180-200 g, were given furosemide and digoxin at doses of 30 mg/kg (i.p.) and 0.25 mg/kg (i.p.) daily for 14 days. After 14 days K,Mg L-, D- and DL-aspartates were administered with simultaneous furosemide and digoxin treating at dose of 100 mg/kg (i.v.), which corresponds to 46.95 mg of Mg aspartate (i.e. Mg \= 3.96 mg) and 53.05 mg of K aspartate (i.e. K \= 12.12 mg) per kg bodyweight. Erythrocyte, plasma and urine Mg levels were measured by colorimetric assay using the method based on the staining reaction of Mg and thiazole yellow. Myocardium Mg and K content and erythrocyte K levels were determined by flame atomic absorption spectroscopy. The level of amine nitrogen was measured by colorimetric assay using the method based on the staining reaction with ninhydrin. It was shown that K,Mg L-aspartate administration leads to higher compensation of K and Mg deficiency in rats with furosemide and digoxin induced K and Mg depletion, as compared with D- and DL-stereoisomers. According to the K and Mg deficiency correction rate, K,Mg aspartates may be ranged in the following order: K, Mg L-aspartate > K,Mg DL-aspartate > K,Mg D-aspartate. It was shown that after administration of K,Mg L-aspartate, daily urine excretion of amine nitrogen and Mg is less than after D- and DL-stereoisomer administration. According to the quantity of excreted amine nitrogen and Mg in urine, K,Mg aspartates may be ranged in the following order: K,Mg D-aspartate \= K, Mg DL-aspartate > K,Mg L-aspartate. So, K,Mg L-aspartate is more beneficial in the treatment of several forms of primary Mg and K deficiency than K,Mg DL-aspartate and K, Mg D-aspartate.
Keywords : digoxin, furosemide, L-, D- and DL-isomers of aspartic acid, potassium and magnesium aspartate, potassium and magnesium deficiencies, rats
Pictures
Figure 1 The experimental design.
Figure 2 Erythrocyte Mg deficiency correction rate
in digoxin treated rats after intravenously administered K,Mg L-,
D- and DL-aspartate stereoisomers (expressed as a delta percentage
of the control). Vertical strokes are ±SEM. Black and white
vertical fingers are beginning of digoxin and K,Mg aspartate
treatment, respectively. * Significantly different K,Mg L-, D- and
DL-aspartate groups vs. control group; ** Significantly different
K,Mg L-, D- and DL-aspartate groups vs. digoxin controls;
§ Significantly different K,Mg L-aspartate group vs.
D-aspartate group; # Significantly different K,Mg
L-aspartate group vs. DL-aspartate group (one-way ANOVA with post
hos Scheffé test, p < 0.05).
Figure 3 Erythrocyte K level in digoxin treated rats
after intravenously administered K,Mg L-, D- and DL-aspartate
stereoisomers (measurement after 24 hours). Vertical strokes are
± SEM. * Significantly different K,Mg L-, D- and DL-aspartate
groups vs. control group; ** Significantly different K,Mg L-, D-
and DL-aspartate groups vs. digoxin control (one-way ANOVA with
post hos Scheffé test, p < 0.05).
Figure 4 Heart K level in digoxin treated rats after
intravenously administered K,Mg L-, D- and DL-aspartate
stereoisomers (measurement after 24 hours and 1 week). Vertical
strokes are ± SEM. * Significantly different K,Mg L-, D- and
DL-aspartate groups vs. control group; ** Significantly different
K,Mg L-, D- and DL-aspartate groups vs. digoxin controls;
§ Significantly different K,Mg L-aspartate group vs.
D-aspartate group (one-way ANOVA with post hos Scheffé test, p <
0.05).
Figure 5 Erythrocyte Mg deficiency correction rate
in furosemide treated rats after intravenously administered K,Mg
L-, D- and DL-aspartate stereoisomers (expressed as a delta
percentage of the control). Vertical strokes are ± SEM. Black
and white vertical fingers are beginning of furosemide and K,Mg
aspartate treatment, respectively. * Significantly different K,Mg
L-, D- and DL-aspartate groups vs. control group; ** Significantly
different K,Mg L-, D- and DL-aspartate groups vs. digoxin controls;
§ Significantly different K,Mg L-aspartate group vs.
D-aspartate group; # Significantly different K,Mg
L-aspartate group vs. DL-aspartate group (one-way ANOVA with post
hos Scheffé test, p < 0.05).
Figure 6 Content of urine amine nitrogen after
single intravenously administered K,Mg L-, D- and DL-aspartate
stereoisomers. Vertical strokes are ±SEM. * Significantly different
K,Mg D- and DL-aspartate groups vs. control group; §
Significantly different K,Mg L-aspartate group vs. D-aspartate
group (one-way Anova with post hos Scheffé test, p < 0.05).
Figure 7 Content of urine Mg after single
intravenously administered K,Mg L-, D- and DL- aspartate
stereoisomers. Vertical strokes are ±SEM. * Significantly different
K,Mg D- and DL-aspartate groups vs. control group; §
Significantly different K,Mg L-aspartate group vs. D-aspartate
group (one-way Anova with post hos Scheffé test, p < 0.05).
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