Lead alters structure and function of mouse flexor muscle.

Abstract

To evaluate the effect of long-term exposure to heavy metals on skeletal muscle, chronic subcutaneous injections for 7 days of two level treatments (low dose, 0.1 mg/kg and high dose, 1 mg/kg) of lead acetate were investigated. Comparative analyses of in situ dorsiflexor muscle isometric contractile characteristics were studied in urethane-anesthetized (2 mg/g, i.p.) control and lead-exposed male mice. Control muscle-twitch tension reached an average of 1.81 +/- 0.06 g. Chronic lead (Pb2+) treatments did not affect muscle contractile speed, but reduced significantly the twitch tension in both high and low doses when compared to control animals. This effect was in a dose-dependent manner; 1.21 +/- 0.07 g for low dose and 0.90 +/- 0.05 g for high dose. These chronic Pb2+ treatments accelerated muscle fatigue after 250 stimuli (25 Hz for 10 sec) in both the low and high doses equally. However, marked elevation in tetanic (25 Hz) specific tension were observed in the high-dose, chronically treated animals, indicating some changes in contractile apparatus function. The high dose of chronic Pb2+ treatment induced ultrastructural changes, including reduced number of synaptic vesicles, disruption of mitochondria and increased number of smooth endoplasmic reticulum and myelin-like figures in the intramuscular axons and neuromuscular junctions. Chronic Pb2+ treatment caused extensive disruption of the sarcoplasmic mitochondria and increased the number of myelin-like figures in the muscle. These results suggest that exposure to Pb2+ at a low concentration can compromise the in situ skeletal muscle isometric contraction.