ABSTRACT
This study describes the effects of Bothrops marajoensis venom (Marajó lancehead) on isolated neuromuscular preparations of chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND). At low concentrations (1µg/ml for CBC and 5µg/ml for PND), the venom exhibited a neuromuscular blocking without any damaging effect on the muscle integrity. At higher concentration (20µg/ml for PND), together with the neuromuscular blockade, there was a moderate myonecrosis. The results show differences between mammalian and avian preparations in response to venom concentration; the avian preparation was more sensitive to venom neurotoxic effect than the mammalian preparation. The possible presynaptic mechanism underlying the neuromuscular blocking effect was reinforced by the observed increase in MEPPs at the same time (at 15min) when the facilitation of twitch tension occurred. These results indicate that the B. marajoensis venom produced neuromuscular blockade, which appeared to be presynaptic at low concentrations with a postsynaptic component at high concentrations, leading to muscle oedema. These observations demand the fractionation of the crude venom and characterization of its active components for a better understanding of its biological dynamics.
ABSTRACT
Recently, we demonstrated that verapamil, an L-type Ca2+ channel blocker, inhibits the activation of splenic lymphocytes during Walker 256 ascitic tumor development in adult rats. In the present study we have analyzed the changes in spleen size, splenic lymphocyte proliferation, white pulp organization and relative size as well as food intake, and levels of blood haemoglobin in Walker 256 tumor bearing rats. These rats displayed a spleen enlargement associated with a significant increase in white pulp area and TCD8+ lymphocyte proliferation. Levels of interferon-gamma, but not of interleukin-10, were elevated in tumor bearing rats, indicating a Th1-type immune response. These manifestations were accompanied by reduced food intake and anaemia. Treatment of tumor bearing rats with verapamil avoided spleen enlargement and increased expression of cytokines, as well as the splenic TCD8+ lymphocyte proliferation. In addition, verapamil treatment promoted an exacerbation of the anorexia and anaemia caused by Walker tumor development. No such effect was observed in control rats treated with verapamil. Taken together, these findings suggest that verapamil inhibits the immune response to cancer, resulting in an increase of the systemic effects induced by Walker 256 tumor.
