Rocha e Silva, the snake venom and 50th anniversary of bradykinin discovery

In this article we emphasize the importante of the snake venom toxins for the development of the autopharmacology concept (Sir Henry Dale, 1933) and how they led to the discovery of bradykinin and to the development of the first active-site directed inhibitor of the angiotensin converting enzyme. We also describe the most recent development concerning the possible role of bradykinin potentiating peptides from Bothrops jararaca venom for the cardiovascular pharmacology. A fundamental step leading to what can be considered one of the most significant contributions given by Brazilian scientists to biomedical sciences, was originated in the efforts of Rocha e Silva to identify and characterize the actors involved in anaphylaxis. His main scientific motivation and efforts which influenced a whole generation of prominent Brazilian scientists, should be reminded when we are commemorating the 50th anniversary of the bradykinin discovery. One important consequence of the use of the Bothrops jararaca venom leading to the discovery of bradykinin was the development of captopril, the most successful drug used by milions of people all over the world to treat arterial hypertension. The purpose of this article is to dissect some of the historical background which aim to stress the need for the adequate scientific environment allowing the privileged scientific minds to uncover secrets of Nature for the benefit of mankind.

Distribution of 131I-labeled Bothrops erythromelas venom in mice

Bothrops erythromelas is responsible for many snake bites in northeastern Brazil. In the present study we determined the in vivo distribution of the venom following its subcutaneous injection into mice. B. erythromelas venom and albumin were labeled individually with I by the chloramine T method, and separated in a Sephacrylr S-200 column. The efficiency of labeling was 68 percent. Male Swiss mice (40-45 g), which had been provided with drinking water containing 0.05 percent KI over a period of 10 days prior to the experiment, were inoculated dorsally(sc) with 03. ml (2.35 x 10(5) cpm/mouse) of I-venom (N=42), I-albumin or I (controls, N=28 each). Thirty minutes and 1, 3, 6, 12, 18 and 24 h after inoculation, the animals were perfused with 0.85 percent NaCl and skin and various organs were collected in order to determine radioactivity content. There was a high rate of venom absorption in the skin (51 percent) within the first 30 min compared to albumin (20.1 percent) and free iodine (8.2 percent). Up to the third hour after injection there was a tendency for venom and albumin to concentrate in the stomach (3rd h), small intestine (3rd h) and large intestine (6th h). Both control groups had more radioactivity in the digestive tract, especially in the stomach, but these levels decreased essentially to baseline by 12-18 h postinjection. In the kidneys, the distribution profiles of venom, albumin and iodine were similar. Counts at 30 min postinjection were low in all three groups (1.37, 1.86 and 0.77, respectively), and diminished to essentially 0 percent by 12-18 h. Albumin tended to concentrate in muscle until the 3rd h postinjection (1.98 percent). There was a low binding of labeled venom is the liver (<0.54 percent), thyroid (<0.11 percent) and lungs (<0.08 percent), and no iodinated venom was detected in brain, heart, diaphragm, spleen or bladder. The low venom binding observed in most internal organs, comparable to that of albumin, suggests that B. erythromelas venom does not specifically target most internal organs. That is, the systemic effects of envenomation are mainly due to an indirect action.