Toxi can Vol . 27, No. 7, pp. 735- 745, 1989 . 0041- 0101/ 89 $3. 00+ . 00 Pr i nt ed in Gr eat Bri t ai n . ® 1989 Per gaown Pr mpi c MYONECROSI S I NDUCED IN MI CE BY A BASI C MYOTOXI N I SOLATED FROM THE VENOM OF THE SNAKE BOTHROPS NUMMI FER ( J UMPI NG VI PER) FROM COSTA RI CA J OSt MARf A GuTI T RREz , ' FERNANDO CHAVES, ' Jost ANTONI o GENT?, ' BRUNO LOMONTE, ' ZI ANNE CAMACHO ' and KARL SCHOSI NSKy 2 ' I nst i t ut o Cl odom iro Pi cado, and 2 Depart ament o de Anal i si s Cl i ni cos, Facul t ad de M i cr obi ol ogi a, Uni ver si dad de Cost a Ri ca, San José, Cost a Ri ca ( Accept ed f or publ i cat i on 29 December 1988) J . M . GuTd : RREz , F . CHAVEs , J . A . GENT:, B . LomoNTE, . Z. CAMACHO and K . SCHOSI NSKY. Myonecr osi s i nduced in m i ce by a basi c myot oxi n i sol at ed f r om t he venomof t he snake Bot hr ops numm i f er (j umpi ng vi per ) f r om Cost a Ri ca . Toxi con 27, 735- 745 . 1989 . - The mode of act i on of a basi c myot oxi n i sol at ed f r om Bot hr ops numm i f er venomwas st udi ed . Thi s myot oxi n is a basi c pol ypep- t i de of 13, 000 mol .wt, with a hi gh cont ent of l ysi ne and aspar t at c, as wel l as of hydr ophobi c am i no aci ds . It l acked phosphol i pase A 2 act i vi t y when t est ed on sever al subst r at es at di f f er ent pH val ues . Upon i .m . i nj ect i on i nt o m i ce, t he t oxi n i nduced ear l y morphol ogi cal al t er at i ons t ypi f i ed by ` del t a l esi ons' in t he per i pher y of muscl e f i ber s, an i ndi cat i on t hat t he pl asma membr ane was t he first cel l ul ar st r uct ur e t o be af f ect ed . Af t er war ds, necr ot i c cel l s had a cl umped appear ance, whi ch t hen changed to a mor e hyal i ne hi st ol ogi cal pat t er n . Remov al of necr ot i c mat eri al by phagocyt es was f ol l owed by skel et al muscl e r egener at i on, with t he pr esence of myobl ast s, myot ubes and f ul l y r egener at ed myof i bers . The t oxi n i nduced a r api d and dr ast i c dr op in muscl e cr eat i ne and cr eat i ne ki nase cont ent s of i nj ect ed muscl e, as wel l as an i ncr ease in ser um l evel s of t he enzymes l act i c dehydr ogenase and cr eat i ne ki nase . Mor eover , t ot al muscl e cal ci um i ncr eased si gni f i cant l y af t er t oxi n adm i ni st r at i on . My o- t oxi n i nduced a dose- dependent r el ease of per oxi dase ent r apped in l i posomes made f r om muscl e phosphol i pi ds . The l ack of phosphol i pase A 2 act i vi t y in t hi s t oxi n, t oget her wi t h t he obser vat i on t hat it behaved as an amphi phi l i c pr ot ei n in char ge- shi f t el ect r ophor esi s, suggest s t hat it m i ght penet r at e and di sor gani ze muscl e pl asma membr ane by means of a hydr ophobi c i nt er act i on . I NTRODUCTI ON MYoNEc Ros l s occur s in a var i et y of pat hol ogi c condi t i ons, such as muscul ar dyst r ophy and i schem i a, as wel l as af t er adm i ni st r at i on of sever al dr ugs, t oxi ns and venoms . Among t hese agent s, snake venoms and, mor e par t i cul ar l y, t oxi ns i sol at ed f r om t hese venoms, have become usef ul t ool s in t he devel opment of experi ment al model s f or t he st udy of muscl e degener at i on and r egener at i on ( HARRI S et al ., 1980; GuTt t RREZ et al ., 1984x) . Sever al myot oxi ns have been i sol at ed f r om snake venoms . Some of t hem ar e phosphol i - pases A 2 whi ch exer t neur ot oxi ci t y, such as not exi n ( HARRI S et al ., 1975) , t ai poxi n ( HARRI S 735