Emetine Myopathy in the Rat

Abstract

(–)‐Emetine (0.25‐2.0 mg/kg i.p.) was administered to rats for up to 220 days. At doses of 1.0 mg/kg or less, the animals continued to gain weight but more slowly than the untreated control animals. The physiological changes in the muscles from these animals were minimal; there was a small reduction in both the resting membrane potential and in the maximum rate of rise of the action potential. There was no atrophy or loss of muscle fibres although in the occasional muscle, hyaline fibres, necrotic fibres and split fibres were observed. There was a focal loss of myofibrillar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH‐TR) in Type II and Type III fibres, but no such loss in Type I fibres. The animals receiving 2.0 mg/kg of (–)‐emetine gained weight slowly for up to 20 days but then rapidly lost weight and by 30 days they were weak and emaciated. The muscles from these animals were severely atrophied and the total muscle wet weight was reduced by almost 20%. The strength of the muscles from these animals was measured in vitro using direct stimulation. They were weaker than normal both in absolute terms and when expressed in terms of tension developed/unit wet weight. There was no evidence of either functional or structural denervation but surgically denervated muscles from animals in this group were indistinguishable from denervated muscles from normal rats. Severe structural damage was obvious in the fibres of both extensor digitorum longus and soleus. Necrotic, hyaline and splitting fibres were common and the focal loss of myofibrillar ATPase and NADH‐TR activity was extensive and occurred in Type I fibres as well as in Type II and Type III fibres. It is concluded that the muscular weakness induced by (–)‐emetine is due to a direct effect on the muscle fibres and that this occurs at a subcellular level. There is no evidence that functional or structural denervation plays any role in the aetiology of emetine myopathy in the rat.

Proliferative and Non-Proliferative Lesions of the Rat and Mouse Soft Tissue, Skeletal Muscle and Mesothelium

“…Comment: Round cytoplasmic basophilic bodies of up to 3µm in diameter composed ultrastructurally of laminated membranous material (spheromembranous bodies) have been described in the muscles of rats treated with agents such as vincristine, colchicine and chloroquine ( 103 Slotwiner et al 1966; 20 Clarke et al 1972; 100 Seiden 1973; 10 Bradley et al 1976).…”

Praziquantel Failure in the Treatment of Fasciola hepatica

“…and more importantly, has been associated with arrhythmias, hypotension , congestive heart failure and death . It is also toxic to skeletal muscle ( 13). No deaths have been reported from emetine in the treatment of fascioHasis.…”

Musculoskeletal System

“…306,307,312 Little or no frank cellular necrosis and inflammation is observed. 316 The ultrastructural changes in skeletal muscles of treated rats included progressive Z line streaming, rod formation, myofilament loss, contraction clumping and extensive membrane proliferation affecting predominantly type I fibers. Studies in rats treated with vincristine have shown that type II fibers are more frequently involved than type I fibers.…”