Banca de QUALIFICAÇÃO: LAÍS ROCHA LIMA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : LAÍS ROCHA LIMA
DATE: 28/11/2023
TIME: 14:00
LOCAL: Google Meet (online)
TITLE:

A DEFINIR

KEY WORDS:

Trans-dehydrocrotonin (t-DCTN); SNEDDS encapsulation; Diabetes mellitus; Hypoglycemic activity; Oxidative stress.

PAGES: 227
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Introduction: The bioactive component trans-dehydrocrotonin (t-DCTN) from the species Croton cajucara Benth (Euphobiceae), has biological activities proven in in vivo experimental models. In this study, the hypoglycemic and antioxidant efficacy of free t-DCTN (15 mg mL-1), solubilized in DMSO (t-DCTN-L) and encapsulated in the SNEDDS system (1 mg mL-1) was evaluated. SNEDDS (self-nanoemulsifying drug delivery system) systems are considered advanced alternatives to nanoemulsion-type colloidal formulations, as they are resistant to dilutions in water and pH variations, with stability in the gastrointestinal tract. Objectives: To evaluate the effects of free (t-DCTN-L) and encapsulated (SNEDDS-DCTN) trans-dehydrocrotonin, in an in vivo experimental model of type 1 diabetes mellitus [streptozotocin (STZ)-induced DM1] on biochemical and oxidative stress. Methodology: The t-DCTN carrier colloidal system (SNEDDS-OCP) was obtained by determining the maximum solubility points of the surfactant (Tween 80), in the oily phase [mixture of copaiba oils (OCP) and sunflower oils (OGR)] in neutral aqueous medium. In the diabetes model, adult male Rattus norvegicus albino Wistar strains (260 to 370 g) were used. The groups tested were named: CD (diabetic control); Diabetic control (MTF- 150 mg/kg); Diabetic control Insulin (6UI); CN (normal control); DMSO (0.1 mL/100 g, v.o); SNEDDS-OCP (0.1 mL/100 g, v.o); t-DCTN-L (0.1 mL/100 g, p.o.), SNEDDS-DCTN (0.05 mL/100 g, p.o.); and SNEDDS-DCTN (0.1 mL/100 g, p.o.). The animals (n= 9 to 10) were maintained under monitored conditions of temperature (24±1 ºC) and light/dark cycle (12 h), with free access to food (Purina®). After fasting (12 h), they received 45 mg kg-1 (i.p.) of STZ diluted in citrate buffer pH 4.5. The CN group received only saline. After 72 h, the animals' capillary glycemia was measured (≥250 mg dL-1) and water (mL/day) and food (g/day) intake were determined daily, and body weight gain and capillary glycemia were determined weekly. At the end of treatment (28 days), hematological and biochemical parameters were determined, and the markers: i) cardiac [creatine phosphokinase (CPK); creatine phosphokinase-MB fraction and lactate dehydrogenase (LDH)]; ii) glycemic [serum glucose and glycated hemoglobin-HbA1c (%)]; iii) liver function (aspartate aminotransferase-TGO, alanine aminotransferase-TGP and albumin); iv) renal (urea and creatinine); v) oxidative stress [plasma malondialdehyde (MDAp), plasma nitrite (NO2p) and plasma myeloperoxidase (MPOp)]. Comparisons were carried out via One Way ANOVA test and Tukey post-test. Results: The SNEDDS-OCP system was characterized by surface tension (8.315 x 10-3 g mL-1), viscosity (8.0 x 10-3 cP), pH (5.05±0.02), refractive index (1.490) and droplet diameter (14.8 nm). The in vivo study showed that the animals' weight gain showed a statistical difference by comparison (DEC), the t-DCTN 0.1 group showed greater weight loss (-39.90±8.51), while the CD group Insulin (6UI) presented the highest average weight gain value (94.30g). About food intake. The food intake of the tested groups was higher than the CN group (23.95±0.88) and the SNEDDS-DCTN 0.05 group (44.47±4.96) presented a higher average value. The SNEDDS-DCTN 0.1 (152.08) group had higher water intake and the t-DCTN 0.1 (10.03) group had higher SD. Regarding the relative weight of the heart, the SNEDDS-DCTN 0.05 and t-DCTN 0.1 groups presented a higher average value (0.38g). the SNEDDS-DCTN 0.05 group (4.52g) presented a higher mean value for liver weight. All groups presented DEC to CN for liver and kidney weight. The SNEDDS-DCTN 0.1 (1.23±0.06) and SNEDDS-OCP 0.1 (1.23±0.05) groups presented the highest mean value. Regarding the hematological profile, the treatment groups did not present DEC, for the hematimetric indices and number of platelets. Regarding the leukocyte profile, for the analysis of total leukocytes, neutrophils (U/UL) and neutrophils (%), the t-DCTN 0.1 group presented a higher mean and SD. There was no DEC for Lymphocytes (U/μL) and Lymphocytes (%). The t-DCTN 0.1 group presented a higher mean value for Monocytes (U/μL). Capillary blood glucose analysis, after 7, 14 and 28 days. At times 1, 2, 3 and 4, the groups: SNEDDS-DCTN 0.1; SNEDDS-DCTN 0.05; SNEDDS-OCP 0.1; t-DCTN 0.1; DMSO 0.1; CD; CD (MTF-150mg/kg) and CD Insulin (6UI) presented DEC to CN. At time 4, the SNEDDS-OCP 0.1 group presented the highest mean value (439.50) and the t-DCTN 0.1 highest EP value (45.74). For fasting blood glucose, the SNEDDS-DCTN 0.05 (45.17) group presents the highest EP. All groups presented DEC at CN (158.11±8.84). For Glycated Hemoglobin, all groups presented DEC to CN (5.97±0.37), SNEDDS-OCP 0.1 (10.00) presented the highest average value. Analysis of cardiac markers: CPK, the SNEDDS-OCP 0.1 group (2749.44), presented a higher mean value, and SNEDDS-DCTN 0.1 higher mean EP (296.33). For CK-MB, the SNEDDS-OCP 0.1 (1656.33) group had the highest mean value, the SNEDDS-DCTN 0.05 (179.63) group had the highest mean EP. For LDH, the SNEDDS-DCTN 0.1 group (828.89±309.11) presented DEC to CD Insulin (6UI) (2994.60±998.31). For the renal marker urea, all groups presented high mean values, regarding creatinine analysis, the highest values recorded SNEDDS-DCTN 0.1 (0.39) and t-DCTN 0.1 (0.39). For liver function, the SNEDDS-DCTN 0.1 group (317.78±46.88) presented a higher mean value and higher rate of variation (317.78-46.88) for TGO. For TGP, the groups: SNEDDS-DCTN 0.1 (206.78±28.38); SNEDDS-DCTN 0.05 (224.60±23.07); SNEDDS-OCP 0.1 (251.22±18.09); DMSO 0.1 (254.67±30.04) and CD (189.80±22.13) presented DEC to CN (95.11±10.31). For Albumin, the SNEDDS-DCTN 0.1 group (44.11±11.27) presented the highest mean value and SD. In evaluating Nitrite (nmol/L) the groups: SNEDDS-DCTN 0.1 (2.10); CD (MTF-150 mg/kg) (2.01) and CN (1.75) presented the highest average values. When evaluating the concentration of MPOp (U mL-1), the groups: SNEDDS-OCP 0.1 (27.68), CD Insulin (6UI) (22.56) and t-DCTN 0.1 (14.41), presented higher mean values. When evaluating MDAp levels (nmol/mL), the CD group (MTF-150 mg/kg) presented the highest mean values (8.50 nmol/mL), followed by the SNEDDS- DCTN 0.1 (6.25 nmol/mL), and CD Insulin (6UI) (6.11 nmol/mL). Conclusion: Data analysis showed that there was efficacy in the treatment of diabetes for the groups treated with t-DCTN free and encapsulated, in which the free t-DCTN was more effective, but there was less weight loss. Regarding food intake, the SNEDDS-DCTN 0.05 group had a higher average consumption. Regarding water intake, the SNEDDS-DCTN 0.1 group showed higher consumption. Regarding the relative weight of the organs, for the heart, the groups: SNEDDS-DCTN 0.05 and t-DCTN 0.1 presented the highest average value. The SNEDDS-DCTN 0.05 group had a higher mean value for liver weight and the SNEDDS-DCTN 0.1 and SNEDDS-OCP 0.1 groups had a higher mean value for kidney weight. In hematimetric indices, all treatment groups showed a high number of platelets and the SNEDDS-DCTN 0.1 group showed an increase in MCV, as well as in the hematological leukocyte profile (absence of neutrophilia or marked leukocytosis). However, evident lymphocytosis was observed for both and there was no reduction in urea levels (renal function). In this function, the lowest creatinine levels were obtained with SNEDDS-OCP 0.1 carrier. For cardiovascular function, there was a better response for SNEDDS-DCTN 0.1 (CPK and LDH) and t-DCTN 0.1 (CK-MB). In liver function (TGO and TGP) the group treated with t-DCTN 0.1 showed better results and for albumin SNEDDS-DCTN 0.05 was more effective. As for oxidative stress markers (in vivo), NO and MDA concentration levels were reduced to t-DCTN 0.1; and MPO for SNEDDS-DCTN 0.05.

COMMITTEE MEMBERS:
Presidente - 2492944 - CAROLINE ADDISON CARVALHO XAVIER DE MEDEIROS
Externa à Instituição - MARIA DO CARMO DE CARVALHO E MARTINS - UFPI
Externo à Instituição - VALDIR FLORENCIO DA VEIGA JUNIOR - IME