Inhibitory properties of the anti-bothropic complex from Didelphis albiventrisserum on toxic and pharmacological actions of metalloproteases and myotoxins from bothrops asper venom11Abbreviations:SVMPs, snake venom metalloproteases; ABC, anti-bothropic complex from Didelphis albiventrisserum; DA43, 43-kDa subunit of anti-bothropic complex from D. albiventrisserum; DA45, 45-kDa subunit of anti-bothropic complex from D. albiventrisserum; MHD, dose able to induce a hemorrhagic lesion of 10 mm diameter; BaP1, basic hemorrhagic metalloprotease from Bothrops aspervenom; BaH4, acidic hemorrhagic metalloprotease from B. aspervenom; Basp-I, myotoxin I from B. aspervenom; Basp-II, myotoxin II from B. aspervenom; and Basp-III, myotoxin III from B. aspervenom.

Anti-bothropic complex (ABC) was isolated from the serum of the South American opossum (Didelphis albiventris) by single-step affinity chromatography using a Sepharose-immobilized metalloprotease (BaP1) from Bothrops asperas the binding protein. Biochemical characterization of ABC showed the presence of two glycosylated subunits of 43 and 45 kDa, respectively, with an isoelectric point < 4. The two subunits were separated by ion-exchange HPLC. The N-terminal sequences of both subunits (LKAMDPTPXLWIETESP, where X is Arg-9 and Pro-9, respectively) showed a high degree of identity with other serum inhibitors isolated from different marsupials. Functional studies pointed out that ABC inhibits the hemorrhagic and proteolytic activities on fibrin, fibrinogen, and casein induced by the metalloproteases BaP1 and BaH4 isolated from B. aspervenom. In addition to the anti-hemorrhagic and anti-proteolytic activities, ABC also showed anti-myotoxic, anti-lethal, and anti-edematogenic effects against myotoxic phospholipases A2isolated from the same venom. Moreover, it had inhibitory effects on the phospholipase A2activity of the crude venom as well as the isolated venom phospholipases A2.