Crotoxin modulates metabolism and secretory activity of peritoneal macrophages from Walker 256 tumor-bearing rats

Autor(es)

Faiad, Odair Jorge ; Francisco, Ana Marta Souza Da Cunha ; Brigatte, Patricia ; Curi, Rui ; Sampaio, Sandra Coccuzzo

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 217, p. 10-pg., 2022-08-16.

Resumo

Crotoxin (CTX), the major toxin of Crotalus durissus terrificus snake venom, induces an inhibitory effect on tumor development and modulates the functions of macrophages (Mos), which play a key role as a defense mechanism against tumor growth. In early tumor progression stage, Mos are avidly phagocytic (inflammatory cell), releasing reactive nitrogen intermediates-RNI/ROI and cytokines TNF-alpha, IL-18, and IL-6. However, when the tumor has been developed, tumor-associated Mo (angiogenic cell) presents a decrease in the mentioned activities. We reported that CTX stimulates H2O2 release, NO production and secretion of cytokines by peritoneal Mos obtained from non-tumor-bearing rats. Considering that the mentioned mediators control tumor growth, it is mandatory to investigate whether CTX stimulates the production of these mediators by Mos obtained from tumor-bearing animals. The aim of this work was then to evaluate the CTX effect on metabolism and functions of peritoneal Mos obtained from Walker 256 tumor-bearing rats. For this purpose, male Wistar rats were subcutaneously inoculated in the right flank with 1 mL sterile suspension of 2 x 107 Walker 256 tumor cells. CTX (18 mu g per animal) was subcutaneously administered in two protocols: a) on the 1st day of tumor cell injection and b) on the 4th day of tumor cell inoculation. In both protocols, Mos were obtaining on the 14th day of tumor cell inoculation to evaluate the release of H2O2, NO, and pro-inflammatory cytokines (IL-18, TNF alpha, and IL-6); maximal activity of hexokinase, glucose-6-phosphate dehydrogenase, citrate synthase, and 14CO2 production from [U-14C]-glucose and [U-14C]-glutamine. The treatment with CTX stimulated the release of NO, H2O2, and cytokines, and glucose and glutamine metabolism. Metabolic and functional changes induced by CTX were accompanied by a decrease of tumor growth as indicated by tumor fresh weight and diameter. These results indicate CTX not only as a scientific tool to investigate changes in metabolism and functions of peritoneal Mos but also for a better understanding of the mechanisms involved in tumor growth. (AU)

• Processo FAPESP: 07/52447-8 - Participação da lipoxina A4 e das proteínas Rho GTPases no efeito anti-tumoral da crotoxina: estudos in vivo e in vitro
• Beneficiário: Sandra Coccuzzo Sampaio Vessoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/53840-8 - Efeito da crotoxina sobre funcao de macrofagos durante a progressao tumoral.
• Beneficiário: Ana Marta Souza da Cunha Francisco
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 09/52330-9 - Efeito da crotoxina sobre a atividade secretoria de macrofagos peritoneais co-cultivados com celulas tumorais da linhagem llc wrc 256.
• Beneficiário: Sandra Coccuzzo Sampaio Vessoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular