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

Crotoxin (CTX), the major toxin of Crotalus durissus terrificus snake venom, induces an inhibitory effect on tumor development and modulates the functions of macrophages (MØs), which play a key role as a defense mechanism against tumor growth. In early tumor progression stage, MØs are avidly phagocytic (inflammatory cell), releasing reactive nitrogen intermediates-RNI/ROI and cytokines TNF-α, IL-1ß, and IL-6. However, when the tumor has been developed, tumor-associated MØ (angiogenic cell) presents a decrease in the mentioned activities. We reported that CTX stimulates H2O2 release, NO production and secretion of cytokines by peritoneal MØs 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 MØs obtained from tumor-bearing animals. The aim of this work was then to evaluate the CTX effect on metabolism and functions of peritoneal MØs 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 × 107 Walker 256 tumor cells. CTX (18 µg 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, MØs were obtaining on the 14th day of tumor cell inoculation to evaluate the release of H2O2, NO, and pro-inflammatory cytokines (IL-1ß, TNFα, 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 MØs but also for a better understanding of the mechanisms involved in tumor growth.

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

Crotoxin (CTX), the major toxin of Crotalus durissus terrificus snake venom, induces an inhibitory effect on tumor development and modulates the functions of macrophages (MØs), which play a key role as a defense mechanism against tumor growth. In early tumor progression stage, MØs are avidly phagocytic (inflammatory cell), releasing reactive nitrogen intermediates-RNI/ROI and cytokines TNF-α, IL-1β, and IL-6. However, when the tumor has been developed, tumor-associated MØ (angiogenic cell) presents a decrease in the mentioned activities. We reported that CTX stimulates H2O2 release, NO production and secretion of cytokines by peritoneal MØs 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 MØs obtained from tumor-bearing animals. The aim of this work was then to evaluate the CTX effect on metabolism and functions of peritoneal MØs 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 × 107 Walker 256 tumor cells. CTX (18 μg 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, MØs were obtaining on the 14th day of tumor cell inoculation to evaluate the release of H2O2, NO, and pro-inflammatory cytokines (IL-1β, TNFα, 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 MØs but also for a better understanding of the mechanisms involved in tumor growth.

Salinity induction of recycling Crassulacean acid metabolism and salt tolerance in plants of Talinum triangulare.

Background and Aims: Crassulacean acid metabolism (CAM) can be induced by salinity, thus conferring the plant higher water-use efficiency. Talinum triangulare does not frequently encounter salt in its natural habitat but is cultivated in soils that may become salinized. Here we examined whether plants of T. triangulare can grow in saline soils and show salt-induced CAM. Methods: Leaf gas exchange, carbon isotopic ratio (δ13C), nocturnal acid accumulation (ΔH+), water relations, photosynthetic pigment and mineral contents, leaf anatomy and growth were determined in greenhouse in plants irrigated with 0, 150, 300 and 400 mm NaCl. Key Results: Salinity reduced gas exchange and induced CAM, ΔH+ reaching 50.2 µmol H+ g-1 fresh mass under 300 mm NaCl. No nocturnal CO2 uptake, but compensation, was observed. Values of δ13C were lowest under 0 and 400 mm NaCl, and highest under 150 and 300 mm. The difference in osmotic potential (ψs) between control and treated plants averaged 0.45 MPa for the three [NaCl] values, the decrease in ψs being accounted for by up to 63 % by Na+ and K+. Pigment contents were unaffected by treatment, suggesting lack of damage to the photosynthetic machinery. Changes in stomatal index with unchanged stomatal density in newly expanded leaves suggested inhibited differentiation of epidermal cells into stomata. Whole-leaf and parenchymata thickness increased under 150 and 300 mm NaCl. Only plants irrigated with 400 mm NaCl showed reductions in biomass (stems, 41 %; reproductive structures, 78 %). The K/Na molar ratio decreased with [NaCl] from 2.0 to 0.4. Conclusions: The operation of CAM in the recycling mode was evidenced by increased ΔH+ with no nocturnal CO2 uptake. Talinum triangulare can be classified as a halo-tolerant species based on its low K/Na molar ratio under salinity and the relatively small reduction in growth only at the highest [NaCl].