Avaliação da capacidade antioxidante e anti-inflamatória da Curcuma Longa, em diferentes tecidos de camundongos saudáveis e/ou com colite ulcerativa moderada induzida por sulfato de sódio dextrana

Abstract

This study aimed to evaluate the effects on the redox and inflammation balance of oral consumption of Curcuma longa extract in different tissues of mice with moderate idiopathic ulcerative colitis (IUC) induced by sodium dextran sulfate (3% SSD in water to drink). Initially, the curcuminoids of the various types of Curcuma longa extracts (methanolic, ethanolic, pharmaceutical, hexane, hexanemethanolic) were identified and quantified. The methanolic, hexanemethanolic and ethanolic extracts presented the 3 curcuminois characteristic of C. longa (bisdesmetoxicurcumina, desmethoxycurcumin and curcumin), whereas in the pharmaceutical extract, commercially available, curcumin constituted the major product (> 95%). Then, the work was divided in 2 parts, the first one (G1) was carried out in healthy animals, with the objective of evaluating which form of Curcuma (extract or powder) would present better antioxidant / anti-inflammatory activity and the second one (G2) , aiming to evaluate the effects of Curcuma (pharmaceutical extract) in animals with moderate ulcerative colitis. For statistical analysis in both cases, the normality of the data was evaluated by the Komogorov-Smirnoff test and then the comparison between the groups was performed according to the normal / non-normal distribution, assuming a significance of 5 %. In G1, 15 Swiss male mice, 8 weeks old, were randomized into three groups: Control (C), which received commercial ration; Curcuma extract (Ext), which received 250 mg/kg by weight/day of Curcuma as pharmaceutical extract; and Curcuma powder (Powder), which received 1g / kg of body weight per day of Curcuma in the form of powder, both administrations were made with the commercial ration. The in vivo experimental period lasted 30 days. The growth and glycemia of those animals were evaluated. Also were measured the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), the activities of the superoxide dismutase enzymes (SOD), catalase (CAT) and myeloperoxidase (MPO) in the intestinal, hepatic, cardiac and cerebral tissues. In phase G1 of the study, no growth and glycemia differences were observed between groups. On the other hand, significant improvements were identified among animals that received the pharmaceutical extract, with a decrease in brain MDA levels, compared to the control group (p <0.001), and decrease of H2O2, compared to powdered Curcuma (p <0.005 ). In phase G2, 18 Swiss male mice, 8 weeks old, were randomized into three groups: control (C) - commercial ration; moderate colitis (MC) - animals with moderate IUC + commercial ration; and moderate extract (ExM) - animals with moderate IUC + 250 mg/kg of body weight/day of Curcuma (pharmaceutical extract) prepared with comercial ration. Oral curcuma supplementation occurred for 37 days and IUC induction was performed in the last 7 days of the experiment. In addition to the oxidative profile (MDA, H2O2, CAT, SOD, GSH, GSSG and GSH/GSSG ratio); the inflamatory profile (TNF-, IL-6 e 10 e INF-γ) of intestinal, hepatic, cardiac and brain tissues; it were also evaluated histological aspects in intestinal tissues. IUC was successfully induced. The intestine showed a decrease in the proinflammatory cytokines INF (p <0.05), IL-6 (p <0.05) and TNF (p <0.05), in the redox activity there was increase in the GSH / GSSG ratio <0.01) and decrease in CAT (p <0.01). In the hepatic tissue there was a decrease in TNF (p <0.05), and IL-10 (p <0.05), in the redox activity an increase in CAT (p <0.0001), GSH / GSSG , 0001) and MDA (p <0.0001). In the cardiac tissue there was a decrease in the anti-inflammatory activity in IL-10 (p <0.05), a CAT increase (p <0.0001), MDA (p <0.05) and GSSG (p <0.01). In the brain tissue an increase in INF (p <0,001) and IL-10 (p <0,05) in the redox profile an increase of SOD (p <0,001) and CAT (p <0,01), GSH/GSSG (p <0,01) and decrease of GSSG (p <0,0001). These data together lead to a number of questions regarding the use of Curcuma as a natural anti-inflammatory / anti-inflammatory drug in the treatment of ulcerative colitis with regard to extra-intestinal manifestations seeing tha these data have shown important imbalance in the markers with (Ext_M) administration in animals affected by IUC, with increases in important pro-inflammatory and pro-oxidants markers in the extra-intestinal tissues studied. Finally, these data together confirm the need for a body-wide evaluation.