Pathological responses of rat skeletal muscle to a single subcutaneous injection of a toxin isolated from the venom of the Australian tiger snake, <i>Notechis scutatus scutatus</i>

Clinical and Experimental Pharmacology and Physiology - Tập 2 Số 5 - Trang 383-404 - 1975
John B. Harris1, Margaret A. Johnson1, Evert Karlsson2
1Muscular Dystrophy Group Laboratories, Regional Neurological Centre, Newcastle General Hospital, Newcastle upon Tyne, England
2Department of Biochemistry, University of Uppsala, Uppsala, Sweden

Tóm tắt

SUMMARY1. The pathology of mammalian skeletal muscle following a single subcutaneous injection of a purified toxin from the venom of the Australian tiger snake, Notechis scutatus scutatus, has been investigated.2. The toxin was injected into the antero‐lateral aspect of one hind limb of rats and the effects of the injection on the histology, histo‐chemistry and physiology of the extensor digitorum longus muscles were studied.3. The muscles underwent degenerative necrosis, with oedema and the infiltration of lymphocytes, polymorphs and macrophages within 12–24 h after the injection.4. Three days after injection, the oedema had subsided and the necrotic fibres had been completely destroyed by phagocytes. Small uninucleate cells, with basophilic cytoplasm and vesicular nuclei were present at this stage; on the basis of these criteria they were identified as regenerating myoblasts.5. By 5 days the myoblasts had fused to form myotubes, but differentiation of the myotubes into histochemically distinct muscle fibre types did not commence until around 7 days after the injection.6. Regeneration and differentiation was virtually complete by 21 days after injection.7. Between 3 and 5 days, many of the fibres were sensitive to acetylcholine, and muscle fibre action potentials were resistant to tetrodotoxin. Miniature end‐plate potentials were of low amplitude and frequency; they may have been absent from many fibres.8. By 7–10 days, the proportion of fibres with tetrodotoxin‐resistant action potentials was declining, and acetylcholine sensitivity was less marked; miniature end‐plate potentials, though of normal amplitude, were of reduced frequency. The fibres were virtually normal by 14–21 days.9. It is considered likely that these physiological properties were recorded from regenerating muscle fibres that reached maturity by 28 days; the possibility that they were recorded from functionally denervated fibres is discussed.10. The rapid rate of regeneration and differentiation of the toxin‐damaged muscle was sustained only if the peripheral nerve supply was left intact.11. Preliminary results suggested that mitochondria‐rich fibres were preferentially damaged by the toxin, and that the toxin is less active in vitro than in vivo. These problems are currently being investigated.12. It is concluded that the toxin has a direct myotoxic effect on muscles; the relationship of this effect to the previously described neurotoxic effect is also currently under investigation.

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Tài liệu tham khảo

Adams R. D., 1962, Diseases of Muscle, a Study of Pathology., 135

10.1016/0014-4886(70)90099-3

Allbrook D., 1962, An electronmiscroscopic study of regenerating skeletal muscle., Journal of Anatomy., 96, 137

10.1113/jphysiol.1959.sp006233

Benoit P. W., 1970, Destruction and regeneration of skeletal muscle after treatment with a local anaesthetic, bupivacaine (Marcaine)., Journal of Anatomy., 107, 547

Burstone M. S., 1958, Histochemical comparison of naphthol AS phosphates for the demonstration of phosphatases., Journal of the National Cancer Institute., 20, 601

Burstone M. S., 1958, Histochemical demonstration of acid phosphatases with naphthol AS phosphates., Journal of the National Cancer Institute., 21, 523

10.1016/0035-9203(61)90020-7

Carlson B. M., 1972, Monographs in Developmental Biology., 1

10.3109/10520295109113178

10.1111/j.1476-5381.1973.tb08381.x

10.1113/jphysiol.1962.sp006941

10.1016/0022-510X(74)90041-0

Flax M. H., 1952, Microspectrophotometric analysis of metachromatic staining of nucleic acids., Physiological Zoology., 26, 297, 10.1086/physzool.25.4.30152126

10.1113/jphysiol.1971.sp009582

10.1111/j.1476-5381.1973.tb08168.x

10.1016/0010-406X(70)90040-X

10.1038/newbio243191a0

10.1111/j.1748-1716.1971.tb05091.x

10.1016/0014-4886(74)90015-6

10.1177/14.8.577

Hudgson P., 1973, The Structure and Function of Muscle., 312

10.1007/BF00307202

10.1016/0041-0101(72)90066-9

10.1038/newbio241158a0

10.1113/jphysiol.1956.sp005555

10.3109/10520294809106232

Nastuk W. L., 1953, Membrane potential changes at a single muscle end‐plate produced by transitory application of acetylcholine with an electrically controlled microjet., Federation Proceedings of the Federation of American Societies for Experimental Biology., 12, 102

Pearse A. G. E., 1972, Histochemistry, Theoretical and Applied., 904

10.1111/j.1748-1716.1971.tb04932.x

10.1111/j.1748-1716.1971.tb04943.x

Reznik M., 1967, Aspect ultrastructural de la dégénérescence du muscle strié ischémié., Annals of Anatomy and Pathology., 12, 209

10.5694/j.1326-5377.1969.tb117007.x

Shilkin K. B., 1973, Clinical Studies in Myology, 136

10.1002/aja.1001100203

10.1016/0041-008X(71)90136-0

Stringer J. M., 1972, Myonecrosis induced by rattlesnake venom,., American Journal of Pathology., 67, 127

Sugita H., 1967, Exploratory Concepts in Muscular Dystrophy and Related Disorders, 321

10.1016/0022-510X(69)90087-2

10.1113/jphysiol.1960.sp006463

10.3109/15563657008990128

Wachstein M., 1956, Histochemistry of substrate specific phosphatase at a physiological pH., Journal of Histochemistry and Cytochemistry., 4, 424

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Thông tin xuất bản

Clinical and Experimental Pharmacology and Physiology

Tập 2 Số 5

383-404

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