Abstract
In skeletal muscle of seven children treated with valproic acid (VPA) microvesicular
(0.05 - 2 μm) lipid droplets were observed between the myofibrils predominantly adjacent
to the mitochondria. Most of the mitochondria showed ultra-structural abnormalities:
several mitochondria were deformed and in several mitochondria abnormal configuration
of cristae was observed. The size of some organelles reached the 10 - 20 (m length
with normal diameter. The elongated mitochondria were located either in the long axis
of the fibers or in the transverse direction near to the Z discs. In rats receiving
valproic acid intraperitoneally for 14 days in daily dose of 100 mg/kg, steatosis
developed in the liver, and focal lipid droplets could also be found in the skeletal
muscle. The mitochondria of the rat liver appeared as normal, but in muscle the structure
and organization of the cristae were disoriented. These observations show that treatment
with valproate causes a kind of drug-induced mitochondrial cytopathy with microvesicular
lipid deposition in the muscle. The lipid deposits are likely a result of the inhibited
mitochondrial fatty acid oxidation. The formation of the abnormal mitochondrial structure
could serve as background for the visible consequences of affected lipid metabolism.
Key words
Valproic acid - Skeletal muscle - Lipid deposition - Mitochondria - Carnitine