Avaliação do potencial antidiabético da curcumina e aminoguanidina em iogurte, isoladas e co-administradas: alterações metabólicas, estresse glico-oxidativo e função neutrofílica.
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Data
2019-12-17
Autores
Lima, Tayra Ferreira Oliveira de
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Universidade Estadual Paulista (Unesp)
Resumo
O diabetes mellitus (DM) é uma síndrome metabólica crônica, caracterizada principalmente por hiperglicemia. A hiperglicemia crônica é um dos principais fatores envolvidos na instalação do estresse glico-oxidativo, o qual está implicado no desenvolvimento das complicações micro e macrovasculares do DM, as quais resultam em morbidade e mortalidade significativas. Portanto, o tratamento da doença tem como principal objetivo a manutenção dos níveis glicêmicos próximos a normalidade e a atenuação do estresse glico-oxidativo. A curcumina, apresenta potencial efeito antidiabético e antioxidante. Já a aminoguanidina é um dos agentes mais utilizados para prevenir a formação de produtos finais da glicação avançada (AGE), in vitro e em modelos animais. Esse estudo investigou em ratos, o potencial antidiabético da curcumina e/ou aminoguanidina incorporadas no iogurte, avaliando parâmetros relacionados às alterações do controle glicêmico, estresse glico-oxidativo (plasma, fígado e rim) e parâmetros da função neutrofílica (exsudato peritoneal). Ratos Wistar, não diabéticos e diabéticos (estreptozotocínico) não tratados, receberam apenas iogurte e os diabéticos tratados receberam: insulina (4U/dia); 90 mg/kg de curcumina; 50 mg/kg de aminoguanidina; 90 mg/kg de curcumina e 50 mg/kg de aminoguanidina; 100 mg/kg de aminoguanidina; e 90 mg/kg de curcumina e 100 mg/kg de aminoguanidina; os tratamentos foram realizados durante 45 dias. Os parâmetros analisados foram: (i) fisiológicos: peso corporal; (ii) bioquímicos: glicemia, hemoglobina glicada (HbA1c), frutosamina, colesterol total, colesterol-HDL, colesterol-não HDL, triacilgliceróis (TAG), alanina (ALT) e aspartato (AST) aminotransferases, fosfatase alcalina (ALP) e proteinúria; iii) bioquímicos relacionados ao estresse glico-oxidativo e defesas antioxidantes: substâncias reativas ao ácido tiobarbitúrico (TBARS), proteínas carboniladas (PCO), AGE fluorescentes, nitrato e nitrito total (NOx), paraoxonase (PON1), superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GSH-Px) e redutase (GSH-Rd), grupos tióis não proteicos e níveis proteicos de receptores de AGE (RAGE e AGE-R1), fator nuclear kappa B (NF-kB) e glioxalase 1 (GLO 1); e (iv) parâmetros relacionados à função neutrofílica: NADPH oxidase fagocítico (NOX2) e mieloperoxidase (MPO). Os animais diabéticos não tratados, apresentaram piora em todos os parâmetros analisados, assim como a instalação do estresse glico-oxidativo, contudo apresentaram um mecanismo compensatório ao estresse oxidativo com aumento nas atividades de GSH-Px e GSH-Rd. O tratamento com insulina foi eficaz na melhoria de todos os parâmetros analisados. O tratamento com curcumina promoveu melhoria nos biomarcadores fisio-metabólicos e do estresse glico-oxidativo e o tratamento com a aminoguanidina nos biomarcadores metabólicos, do estresse glico-oxidativo e da função neutrofílica. Os tratamentos com as associações também foram benéficos frente aos parâmetros alterados no DM experimental. Contudo, o tratamento que apresentou mais benefícios foi a associação curcumina com 50 mg/kg de aminoguanidina, pois foi promissor no controle glicêmico, na redução do estresse glico-oxidativo e na melhoria da função neutrofílica, apresentando respostas mais eficazes que os respectivos compostos administrados isoladamente. Desta forma, demonstrando potencial na atenuação e/ou prevenção das complicações do DM. Considerando os resultados na função neutrofílica e a semelhança estrutural entre aminoguanidina e metformina também avaliamos o tratamento com 250 mg/kg de metformina e sua associação com 90 mg/kg de curcumina, incorporadas no iogurte, durante 45 dias, entretanto, não foi observado melhorias significativas na função neutrofílica.
Diabetes mellitus (DM) is a chronic metabolic syndrome characterized mainly by hyperglycemia. Chronic hyperglycemia is one of the main factors involved in the installation of glycoxidative stress, and it is implicated in the development of micro and macrovascular complications of DM, which result in significant morbidity and mortality. Therefore, the treatment of the disease has as main objective the maintenance of glycemic to levels near to normality and the attenuation of glycoxidative stress. Curcumin has potential antidiabetic and antioxidant effects. Aminoguanidine is one of the most used agents to prevent the formation of advanced glycation end products (AGE), in vitro and animal models. This study investigated in rats the antidiabetic potential of curcumin and/or aminoguanidine incorporated into yoghurt, evaluating parameters related to changes in glycemic control, glycoxidative stress (plasma, liver and Kidney) and parameters of neutrophil function (peritoneal exudate). Rats Wistar, non-diabetic and diabetic (streptozotocinic) untreated received alone yoghurt and treated-diabetic received: insulin (4U/day); 90 mg/kg curcumin; 50 mg/kg aminoguanidine; 90 mg/kg curcumin and 50 mg/kg aminoguanidine; 100 mg/kg aminoguanidine; and (vi) 90 mg/kg curcumin and 100 mg/kg aminoguanidine; the treatments were performed for 45 days. The parameters analyzed were: (i) physiological: body weight; (ii) biochemicals: glycemia, glycated hemoglobin (HbA1c), fructosamine, total cholesterol, HDL-cholesterol, non-HDLcholesterol, triglycerides (TAG), alanine (ALT) and aspartate (AST) aminotransferases, alkaline phosphatase (ALP) and proteinuria; iii) biochemical related to glycoxidative stress and antioxidant defenses: thiobarbituric acid reactive substances (TBARS), protein carbonyl groups (PCO), fluorescent AGE, total nitrate and nitrite (NOx), paraoxonase (PON1), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and reductase (GSH-Rd), non-protein thiol groups and protein levels of AGE (RAGE and AGE-R1) receptors, factor nuclear kappa B (NF-kB) and glyoxalase 1 (GLO 1); and (iv) parameters related to neutrophil function: phagocytic NADPH oxidase (NOX2) and myeloperoxidase (MPO). The untreated-diabetic animals showed worsening in all analyzed parameters, as well as the installation of glycoxidative stress, however it presented a compensatory mechanism against oxidative stress with increses in the activities of GSH-Px and GSH-Rd. The treatment with insulin was effective in improve all analyzed parameters. Treatment with curcumin promoted improvement in physio-metabolic biomarkers and glycoxidative stress, and treatment with aminoguanidine in metabolic biomarkers, glycoxidative stress and neutrophil function. The treatments with the associations were also beneficial for the altered parameters in experimental DM. However, the most beneficial treatment was the combination of curcumin with 50 mg/kg aminoguanidine; it was promising in glycemic control, reduction of glycoxidative stress and improvement of neutrophil function, presenting more effective responses than the respective compounds administered alone. Therefore, demonstrating potential attenuation and/or prevention of complications of DM. Considering the results on neutrophilic function and the structural similarity between aminoguanidine and metformin we also evaluated treatment with 250 mg/kg metformin and its association with 90 mg/kg curcumin, incorporated in yoghurt, for 45 days, however, no improvement was observed in neutrophil function
Diabetes mellitus (DM) is a chronic metabolic syndrome characterized mainly by hyperglycemia. Chronic hyperglycemia is one of the main factors involved in the installation of glycoxidative stress, and it is implicated in the development of micro and macrovascular complications of DM, which result in significant morbidity and mortality. Therefore, the treatment of the disease has as main objective the maintenance of glycemic to levels near to normality and the attenuation of glycoxidative stress. Curcumin has potential antidiabetic and antioxidant effects. Aminoguanidine is one of the most used agents to prevent the formation of advanced glycation end products (AGE), in vitro and animal models. This study investigated in rats the antidiabetic potential of curcumin and/or aminoguanidine incorporated into yoghurt, evaluating parameters related to changes in glycemic control, glycoxidative stress (plasma, liver and Kidney) and parameters of neutrophil function (peritoneal exudate). Rats Wistar, non-diabetic and diabetic (streptozotocinic) untreated received alone yoghurt and treated-diabetic received: insulin (4U/day); 90 mg/kg curcumin; 50 mg/kg aminoguanidine; 90 mg/kg curcumin and 50 mg/kg aminoguanidine; 100 mg/kg aminoguanidine; and (vi) 90 mg/kg curcumin and 100 mg/kg aminoguanidine; the treatments were performed for 45 days. The parameters analyzed were: (i) physiological: body weight; (ii) biochemicals: glycemia, glycated hemoglobin (HbA1c), fructosamine, total cholesterol, HDL-cholesterol, non-HDLcholesterol, triglycerides (TAG), alanine (ALT) and aspartate (AST) aminotransferases, alkaline phosphatase (ALP) and proteinuria; iii) biochemical related to glycoxidative stress and antioxidant defenses: thiobarbituric acid reactive substances (TBARS), protein carbonyl groups (PCO), fluorescent AGE, total nitrate and nitrite (NOx), paraoxonase (PON1), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and reductase (GSH-Rd), non-protein thiol groups and protein levels of AGE (RAGE and AGE-R1) receptors, factor nuclear kappa B (NF-kB) and glyoxalase 1 (GLO 1); and (iv) parameters related to neutrophil function: phagocytic NADPH oxidase (NOX2) and myeloperoxidase (MPO). The untreated-diabetic animals showed worsening in all analyzed parameters, as well as the installation of glycoxidative stress, however it presented a compensatory mechanism against oxidative stress with increses in the activities of GSH-Px and GSH-Rd. The treatment with insulin was effective in improve all analyzed parameters. Treatment with curcumin promoted improvement in physio-metabolic biomarkers and glycoxidative stress, and treatment with aminoguanidine in metabolic biomarkers, glycoxidative stress and neutrophil function. The treatments with the associations were also beneficial for the altered parameters in experimental DM. However, the most beneficial treatment was the combination of curcumin with 50 mg/kg aminoguanidine; it was promising in glycemic control, reduction of glycoxidative stress and improvement of neutrophil function, presenting more effective responses than the respective compounds administered alone. Therefore, demonstrating potential attenuation and/or prevention of complications of DM. Considering the results on neutrophilic function and the structural similarity between aminoguanidine and metformin we also evaluated treatment with 250 mg/kg metformin and its association with 90 mg/kg curcumin, incorporated in yoghurt, for 45 days, however, no improvement was observed in neutrophil function
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Palavras-chave
curcumina, aminoguanidina, diabetes mellitus, estresse glico-oxidativo, neutrófilos, curcumin, aminoguanidine, diabetes mellitus, glycoxidative stress, neutrophils