- Email: [email protected]
Comparative pharmacological effects of Carybdea rastoni and Chironex fleckeri on rat aorta
Report and Abstracts
549
in the presence of 25 pl/ml of MTX1 . Degranulation and leakage of cytoplasmic contents in hGLCs resulted from 1 hr incubation at the concentration of 12 .5 pl/ml of MTXI . Subsequently 'ghost GLCs' and wmplete loss of cellular architecture in the intoxicated hCLCs were observed after 4 hr incubation at this concentration. We concluded from our preliminary experiments that MTX1 possesses a strong haemolytic effect to hRBC, which is time and dose dependent . hGLCa are more resistant to MTX 1 . However, with higher concentrations and longer exposure time, they are also affected by MTXI . The haematoxic mechanism of MTXI is likely to be mediated through its damaging effect on certain structural/functional components of cell membrane of both hRBCs and hGLCs, but details need yet to be elucidated.
light and electron microscopic studies of the effects of the venom from Pseudechis sustralis in the marine soleur muscle . S . Z . J . Crux,' P. GOPALAKRISHNAKONE~ and M . C . E, Gw~' (Venom and Toxin Research Group, Departments of ' Pharmacology, and ZAnatomy, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 0511) . Trrn vExoM of Pseudechis australis can cause skeletal muscle paralysis because of its phospholipase AZ (PLA :) as well as myotoxic activity. The pathological changes in skeletal muscle and motor endplate were investigated using light electron microscopy. A sub-lethal dose of the crude venom (0 .5 mg/kg) was administered by i .p . injection into 62 mice . Almost all mice had myoglobinuria with subsequent reddish pigment on filter paper after 2-~ hr . At 0 .5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hr and 1, 3, 6 and 10 weeks intervals after intoxication, two or three mice at each time interval were anaesthetized with ether and perfused via the left ventricle with 10% formalin for L.M . and 2% paraformaldehyde and 3% glutaraldehyde in 0 .1 M sodium buffer for E .M . After perfusion for 20-30 min, the soleus muscle was dissected out and processed for microscopic examination . Under light microscopy, vacuolation of muscle fibres (HBcE stain) was found within 2~ hr post-injection . From 4 hr to 1 week extensive changes were observed, including loss of normal striations, oedema and disintegration of fibres and pyknosis . After 3 weeks the myofibrils appeared normal in comparison to control tissue, indicating regeneration of the muscle. Electron microscopic examination revealed changes characterized by disruption of myofibrils and disorganization of A and Z bands, swelling and dissolution of mitochondria . In nerve terminals, there was depletion of vesicles and disruption of mitochondria . Thus the venom of Pseudechis australis induced myodegeneration and necrosis in the soleus muscle at an early stage with depletion of synaptic vesicles and mitochondria damage in motor end-plate, changes which may be attributed to the myotoxic and PLA Z activity of the venom . Supported by National University of Singapore research grant (RP870357).
Comparative pharmacological effects of Carybdea rastoni and Chironex fleckeri on rat aorta. M . T. ELDILA,' M. R . Musr~~,r N . Azrt,w' and I. OrtiMerr' (Departments of ' Biochemistry, and ~ Pharmacology, Faculty of Medicine, University of Malaya, 59100 Kuala Lumpur, Malaysia). AMONG the eight species of jellyfish that have been identified in the waters around West Malaysia, Carybdea rastoni has been reported to be the most dangerous and feared by the fishermen and also beach-Boers . Unlike Chironex fieckeri which has not been reported in Malaysian waters but has been responsible for about 80 deaths in Australia, no deaths have been reported so far with Carybdea rastoni in Malaysia or elsewhere . In this report, a comparative study of the pharmacological effects of Chironex Jleckeri and Carybdea rastoni was carried out on isolated rat aorta . Both species produced marked contractions which differed in their onset and duration . The contraction induced by the toxin from Carybdea (20 pg/ml) was slow in its onset, with a maximum effect reached in 15-20 min. This is in contrast to Chironex (12 pg/ml) toxin which slowed an immediate action within 4 min . For each toxin the contractile effect was partially attenuated following subsequent applications of the toxin . In both cases, contraction was not inhibited by addition of phentolamine (20pM), an a-adrenoceptor antagonist, but was completely inhibited in the presence of verapamil (10 tr M), a calcium channel blocker, and in calcium-free solution. The results suggest that the toxin-induced contractions were mediated by the influx of calcium ions via voltage-dependent calcium channels . Prostaglandin and histamine may also be released during Chironex-induced contraction since treatment with indomethacin (lOltM) and mepyramine (IOpM) attenuated the effects of the toxin. In contrast, pretreatment with either antagonist did not affect the contraction induced by the toxin from Carybdea .
Evaluatèon of trypsin treatment for experimental errvenomation by poisonous snakes of Malaysia . P. KFF and N .-H . TMt (Department of Biochemistry, Faculty of Medicine, University of Malaya, 59100 Kuala Lumpur, Malaysia) . rox s:~ s--e
549
in the presence of 25 pl/ml of MTX1 . Degranulation and leakage of cytoplasmic contents in hGLCs resulted from 1 hr incubation at the concentration of 12 .5 pl/ml of MTXI . Subsequently 'ghost GLCs' and wmplete loss of cellular architecture in the intoxicated hCLCs were observed after 4 hr incubation at this concentration. We concluded from our preliminary experiments that MTX1 possesses a strong haemolytic effect to hRBC, which is time and dose dependent . hGLCa are more resistant to MTX 1 . However, with higher concentrations and longer exposure time, they are also affected by MTXI . The haematoxic mechanism of MTXI is likely to be mediated through its damaging effect on certain structural/functional components of cell membrane of both hRBCs and hGLCs, but details need yet to be elucidated.
light and electron microscopic studies of the effects of the venom from Pseudechis sustralis in the marine soleur muscle . S . Z . J . Crux,' P. GOPALAKRISHNAKONE~ and M . C . E, Gw~' (Venom and Toxin Research Group, Departments of ' Pharmacology, and ZAnatomy, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 0511) . Trrn vExoM of Pseudechis australis can cause skeletal muscle paralysis because of its phospholipase AZ (PLA :) as well as myotoxic activity. The pathological changes in skeletal muscle and motor endplate were investigated using light electron microscopy. A sub-lethal dose of the crude venom (0 .5 mg/kg) was administered by i .p . injection into 62 mice . Almost all mice had myoglobinuria with subsequent reddish pigment on filter paper after 2-~ hr . At 0 .5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hr and 1, 3, 6 and 10 weeks intervals after intoxication, two or three mice at each time interval were anaesthetized with ether and perfused via the left ventricle with 10% formalin for L.M . and 2% paraformaldehyde and 3% glutaraldehyde in 0 .1 M sodium buffer for E .M . After perfusion for 20-30 min, the soleus muscle was dissected out and processed for microscopic examination . Under light microscopy, vacuolation of muscle fibres (HBcE stain) was found within 2~ hr post-injection . From 4 hr to 1 week extensive changes were observed, including loss of normal striations, oedema and disintegration of fibres and pyknosis . After 3 weeks the myofibrils appeared normal in comparison to control tissue, indicating regeneration of the muscle. Electron microscopic examination revealed changes characterized by disruption of myofibrils and disorganization of A and Z bands, swelling and dissolution of mitochondria . In nerve terminals, there was depletion of vesicles and disruption of mitochondria . Thus the venom of Pseudechis australis induced myodegeneration and necrosis in the soleus muscle at an early stage with depletion of synaptic vesicles and mitochondria damage in motor end-plate, changes which may be attributed to the myotoxic and PLA Z activity of the venom . Supported by National University of Singapore research grant (RP870357).
Comparative pharmacological effects of Carybdea rastoni and Chironex fleckeri on rat aorta. M . T. ELDILA,' M. R . Musr~~,r N . Azrt,w' and I. OrtiMerr' (Departments of ' Biochemistry, and ~ Pharmacology, Faculty of Medicine, University of Malaya, 59100 Kuala Lumpur, Malaysia). AMONG the eight species of jellyfish that have been identified in the waters around West Malaysia, Carybdea rastoni has been reported to be the most dangerous and feared by the fishermen and also beach-Boers . Unlike Chironex fieckeri which has not been reported in Malaysian waters but has been responsible for about 80 deaths in Australia, no deaths have been reported so far with Carybdea rastoni in Malaysia or elsewhere . In this report, a comparative study of the pharmacological effects of Chironex Jleckeri and Carybdea rastoni was carried out on isolated rat aorta . Both species produced marked contractions which differed in their onset and duration . The contraction induced by the toxin from Carybdea (20 pg/ml) was slow in its onset, with a maximum effect reached in 15-20 min. This is in contrast to Chironex (12 pg/ml) toxin which slowed an immediate action within 4 min . For each toxin the contractile effect was partially attenuated following subsequent applications of the toxin . In both cases, contraction was not inhibited by addition of phentolamine (20pM), an a-adrenoceptor antagonist, but was completely inhibited in the presence of verapamil (10 tr M), a calcium channel blocker, and in calcium-free solution. The results suggest that the toxin-induced contractions were mediated by the influx of calcium ions via voltage-dependent calcium channels . Prostaglandin and histamine may also be released during Chironex-induced contraction since treatment with indomethacin (lOltM) and mepyramine (IOpM) attenuated the effects of the toxin. In contrast, pretreatment with either antagonist did not affect the contraction induced by the toxin from Carybdea .
Evaluatèon of trypsin treatment for experimental errvenomation by poisonous snakes of Malaysia . P. KFF and N .-H . TMt (Department of Biochemistry, Faculty of Medicine, University of Malaya, 59100 Kuala Lumpur, Malaysia) . rox s:~ s--e