ABSTRACT
Background: Dicrotophos is an organophosphate pesticide whose residue has been detected in most vegetables even in organic samples. Though this pesticide is classified as a highly hazardous Ib organophosphate, it is not banned in many countries including Thailand. Improper use of this chemical exposes the people to it through consumption of contaminated food and water. Some people develop signs of cholinergic syndrome following exposure and some suffer for days from paralysis of respiratory and limb muscles. However, there is no direct evidence indicating muscle weakness through decreased contractile property. All studies in humans thus far were clinically investigated and reported using information from subjective verbal histories. Objective: To investigate the contractile characteristics of skeletal muscles after dicrotophos exposure. Methods: A preliminary study was performed to determine the effective dose of dicrotophos that causes at least 30 % reduction in red blood cell cholinesterase activity. The rats were injected with dicrotophos daily at LD6.25, LD12.5 and LD25 doses for 5 weeks. It was found that the LD12.5 dose caused the effect, starting at the 4th week of injection. Therefore, this dose was injected into the rats before examining the isometric twitch characteristics of gastrocnemius muscle and cholinesterase activity in red blood cells and muscle homogenates. Results: Significant decreases in peak tension and time to peak tension were observed in rats exposed to this dose of dicrotophos. These decreases agreed with cholinesterase activity in RBC and muscle homogenates. Conclusion: Dicrotophos exposure in rats caused decreased contractile activity providing direct evidence implying the muscle weakness often found in humans.
ABSTRACT
The effect of hyperthyroidism on the contractile properties and Ca<SUP>2+</SUP> sequestering abilities by the sarcoplasmic reticulum (SR) in the soleus muscles was examined in rats treated with thyroid hormone (3, 5, 3'-triiodo-L-thyronine, T<SUB>3</SUB>) (300μg/kg body weight) for 3, 7 and 21 days. At the end of a given treatment period, the right or left soleus muscle was mounted isometrically at 30°C, and stimulated directly using supramaximal current intensity. A twitch contraction was elicited by a 1 msec square-wave pulse and a tetanic contraction by 20 Hz stimulation for 600 msec. To evaluate fatigue resistance, muscles were stimulated at 40 Hz for 350 msec with tetani repeated at an interval of 2 sec during a 4-min period. Another soleus muscle was used, for analysis of SR Ca<SUP>2+</SUP> -uptake rate and SR Ca<SUP>2+</SUP> -ATPase activity. Pronounced increases in SR Ca<SUP>2+</SUP> -uptake rate and ATPase activity were observed after T<SUB>3</SUB> treatment periods longer than 6 days. These alterations were accompanied by decreases in twitch and tetanic tension, half-relaxation time, and fatigue resistance. The T<SUB>3</SUB>-treated muscles stimulated at 20 Hz relaxed during the interval between successive stimuli, indicating that the mechanical fusion of tetanic contractions was incomplete. SR Ca<SUP>2+</SUP> uptake rate was significantly correlated both to tetanic tension and to fatigue resistance. These data suggest that there may be a causal relationship between changes in SR Ca<SUP>2+</SUP> uptake and the loss of muscular strength in the hyperthyroid soleus.