The effects of 2,5-hexanedione and acrylamide on myosin heavy chain isoforms of slow and fast skeletal muscles of the rat.

ABSTRACT

We examined the effects of 2,5-hexanedione (2,5-HD) and acrylamide (ACR) on the muscle fiber types and myosin heavy chain (MHC) isoform composition of the slow-twitch soleus and fast-twitch plantaris muscles of rats. We employed two differently designed experiments with respect to the dosage levels and treatment periods for developing clinical neuropathies. When male Wistar rats were subcutaneously injected with 4.5 mmol of 2,5-HD/kg or 0.4 mmol of ACR/kg, 5 days a week, they developed paralysis of the hindlimbs in 4 weeks (high-dosage experiment). When they were subcutaneously injected with 3.5 mmol of 2,5-HD/kg or 0.35 mmol of ACR/kg, 5 days a week, paralysis of the hindlimbs did not develop until 6 weeks (low-dosage experiment). We examined mainly the rats treated with the neurotoxicants for 4 and 8 weeks in the high-and low-dosage experiments, respectively. Significant decreases in the maximum motor conduction velocity of the sciatic nerves were observed in the hindlimbs of the rats in both experiments. The weights of the soleus and plantaris muscles were significantly reduced in the 2,5-HD-treated rats in both experiments, while in the ACR-treated rats, the weights of both muscles decreased only in the low-dosage experiment. We could not detect any changes in the fiber type composition of the muscles by any of the treatments. However, biochemical analysis revealed decreases in the values (percentage) of the relative amounts of fast-type MHC IIa and IIb isoforms to total MHC isoforms in the 2,5-HD-treated rats, but not in the ACR-treated rats in the high-dosage experiment. In contrast, significant differences in the relative amounts of MHC isoforms were not observed after administration of the low dosage of 2,5-HD. These results suggest that 2,5-HD preferentially disorders the muscle fibers which contain the MHC II isoform. These effects may occur only after the relatively acute intoxication of 2,5-HD at a high dosage.