Light and electron microscopic study of the effect of sodium valproate on the quadriceps femoris muscle of rat and the possible protective role of L-carnitine

ABSTRACT

Sodium valproate [VPA] is a broad spectrum antiepileptic drug. Patients especially children who receive VPA for a long time present with myalgia and exercise intolerance. The aim of the present study was to elicit the effect of VPA on the skeletal muscle and the possible protective role of L-carnitine. Fifty male albino rats were used in this study. The animals were divided into two groups group A [control group] and group B [experimental group] which was subdivided into 4 subgroups group B1 and B2 received VPA only [50 mg/kg/day], for 1 and 2 months respectively. Group B3 and B4 received VPA and L-carnitine [300 mg/kg/day] for 1 and 2 months respectively. At the end of the experiment blood samples were collected to evaluate serum VPA levels. Quadriceps femoris muscles [QFM] were dissected and processed for light and electron microscopic [EM] study. In group B1, some QFM fibers showed loss of their striation or longitudinally splitted. Some intermediate muscle fibers appeared to be deficient in succinic dehydrogenase enzyme[S-DH] activity. EM study revealed many lipid droplets and enlarged degenerated mitochondria in-between the myofibrils. The mean serum VPA level was 101.6 +/- 7.88 micro g/ml. In group B2 the majority of muscle fibers were degenerated with mononuclear cellular infiltration and marked decrease in S-DH activity in all types of muscle fibers. Disorganized myofibrils, megamitochondria and lysosomes were seen. The lipid and glycogen granules were increased. There was a non significant increase in the mean serum VPA level [105.01 +/- 6.34 micro g/ml]. On the other hand, there was a highly significant decrease in the mean serum VPA level in group B3 [85.39 +/- 5.93 micro g/ml] and B4 [86.23 +/- 8.39 micro g/ml]. No histological changes were observed in these two groups except that some mitochondria were enlarged in group B4. In conclusion, the use of L-carnitine has a great role in protection against VPA-induced myopathy and it should be prescribed for all patients treated with VPA for long time