Avaliação do metabolismo energético e estresse oxidativo em miocárdio de ratos com diabetes mellitus tipo 1, tratados com geraniol
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Data
2019-03-29
Autores
Carmo, Nágilla Orleanne Lima do
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Universidade Estadual Paulista (Unesp)
Resumo
Diabetes mellitus (DM) é uma desordem metabólica caracterizada pela hiperglicemia persistente, com distúrbios no metabolismo de carboidratos, lipídios e proteínas, resultante de defeitos na secreção de insulina, ação da insulina ou ambos. A utilização de antioxidantes tem contribuído para melhorar a hiperglicemia e também minimizar as complicações diabéticas. Geraniol, um monoterpeno, presente na composição de óleos essenciais de várias plantas medicinais, apresenta ação antioxidante e antihiperglicemiante, sendo capaz de contribuir na terapêutica desta patologia. Este estudo tem como objetivo avaliar o metabolismo energético e estresse oxidativo no miocárdio de ratos com DM tipo 1, tratados com geraniol. Foram utilizados 32 ratos machos, Wistar (± 250g de peso corporal), distribuídos em 4 grupos experimentais (n=8): C (normais, controle); GE (normais, tratados com geraniol); DM (diabéticos, não-tratados); DM-GE (diabéticos, tratados com geraniol). A DM tipo 1 experimental foi induzido através da administração de estreptozotocina (STZ – 60 mg/Kg de peso corporal, i.p., dose única). Os animais dos grupos GE e DM-GE receberam geraniol (200 mg/Kg/dia) via gavagem durante 30 dias e os animais dos grupos C e DM receberam água pelo mesmo procedimento. Durante o período experimental, foram avaliados consumo de água e ração. Após este período, os animais em jejum de 12 horas, foram anestesiados (xilazina e cetamina) e eutanasiados. Foram coletadas amostras séricas para análise da concentração de glicemia e do perfil lipídico e porções de tecido cardíaco para dosagem de glicogênio, triacilgliceróis, proteínas totais, enzimas do metabolismo energético e do estresse oxidativo. Os resultados foram analisados por ANOVA One-way seguido do teste de Tukey para comparação das médias. As diferenças foram consideradas significativas quando p<0.05. Houve redução no consumo alimentar, hídrico e energia ingerida (p<0,05), além de maior peso corporal e ganho de peso em animais diabéticos tratados com geraniol (DM-GE), quando comparados aos animais diabéticos não tratados (DM). A administração de geraniol em DM-GE também promoveu diminuição da glicemia, coleserol, triacilgliceróis, VLDL-colesterol e LDL-colesterol, assim como aumento da concentração sérica de HDL-colesterol (DM-GE), quando comparado ao grupo DM. O grupo DM apresentou menores concentrações cardíacas de glicogênio em relação aos demais grupos, sendo que o tratamento com geraniol aumentou este parâmetro (p<0,05). A concentração cardíaca de triacilgliceróis foi maior (p<0,05) nos grupos DM e DM-GE, diferindo estatisticamente dos demais grupos. A atividade cardíaca tanto da fosfofrutoquinase (PFK) como da piruvato desidrogenase (PiDH) foi menor no grupo DM, tendo aumento na presença de geraniol. Os animais do grupo DM apresentaram maior atividade cardíaca para citrato sintase (CS) e β-hidroxil CoA-desidrogenase (OHADH), e com o uso de geraniol, a atividade destas enzimas diminuiu. A atividade da NADH-desidrogenase (NADH-DH), succinato-desidrogenase (SUC-DH) e ATP-sintase apresentou-se diminuída nos animais do grupo DM e o uso do geraniol restabeleceu a atividade da NADH-DH e ATP-sintase; animais do grupo GE tiveram a atividade da ATP-sintase aumentada, diferindo dos demais grupos. Quanto aos parâmetros do estresse oxidativo, não foram observadas diferenças significativas na atividade das enzimas glutationa reduzida (GSH) e glutationa total (GS total). A administração de geraniol em ratos diabéticos promoveu diminuição da concentração de hidroperóxido de lipídios (HP) e de proteína carbonila (PC) e aumento da atividade das enzimas antioxidantes glutationa peroxidase (GSH-Px) e superóxido dismutase (SOD), quando comparado a animais do grupo DM. Conclui-se que a administração de geraniol reduziu os efeitos prejudiciais observados na condição diabética, através do seu efeito antidiabetogênico e antioxidante.
Diabetes mellitus (DM) is a metabolic disease characterized by persistent hyperglycemia, with disorders in the metabolism of carbohydrates, lipids and proteins, resulting from defects in insulin secretion, insulin action, or both. The use of antioxidants has contributed to improve hyperglycemia and also minimize diabetic complications. Geraniol, a monoterpene, present in the composition of essential oil of various medicinal plants, has oxidant and antihyperglycemic action, being able to contribute in the therapy of this pathology. This study aimed to evaluate the energetic metabolism and oxidative stress in the myocardium of rats with type 1 DM treated with geraniol. 32 male Wistar rats (±250g body weigth), distributed in four experimental groups (n=8): C (normal, control); GE (normal, treated with geraniol); DM (diabetic, untreated); DM-GE (diabetic, treated with geraniol). Experimental type 1 DM was induced by streptozotocin (STZ - 60mg/Kg body weight, i.p., single dose). Animals of the group GE and DM-GE received geraniol (200mg/K/day) by gavage for 30 days and animals of the group C and DM received water by the same procedure. Animals of the group GE and DM-GE received geraniol (200mg/K/day) by gavage for 30 days and animals of the group C and DM received water by the same procedure. During the experimental period, food and water intake were evaluated. After this period the animals, in a 12h fast, were anesthetized and euthanized. Serum samples were collected for glycemia concentration and lipid profile and portions of cardiac tissue for glycogen dosage, triacylglycerols, total proteins, enzymes of energy metabolism and oxidative stress. Results were analyzed by One-way ANOVA followed by Tukey test for comparison of means. The results were considered significant when p<0.05. Decreased in food consumption, water consumption and energy intake (p<0.05), however greater body weight and weight gain in diabetic animals treated with geraniol (DM-GE) compared to untreated diabetic animals (DM). The administration of geraniol in DM-GE also caused a decrease in serum glycemia, cholesterol, triacylglycerols, VLDL-cholesterol and LDL-cholesterol, an increase in serum HDL-cholesterol concentration (DM-GE) when compared to DM group. DM group showed lower cardiac glycogen concentrations in relation to the other groups and the treatment with geraniol increased this parameter (p<0.05). The cardiac concentration of triglycerides was higher (p<0.05) in the DM and DM-GE groups, differing statistically from the other groups. The cardiac activity of both fosfofrutoquinase (PFK) and pyruvate dehydrogenase (PiDH) was lower in the DM group, with an increase in the presence of geraniol. Animals of the DM group showed increased cardiac activity for citrate synthase (CS) and β-hydroxyl CoA dehydrogenase (OHADH) and with the use of geraniol the activity of these enzymes decreased. The activity of NADH-dehydogrenase (NADH-DH), succinate dehydrogenase (SUC-DH) and ATP-synthase were decreased in the animals of the DM group and the use of geraniol reestablished the activity of NADH-DH and ATP-synthase; animals from the GE group had the ATP-synthase activity increased, differing from the other groups. As for the parameters of oxidative stress, no significant differences were observed in the activity of glutathione reduced (GSH) and total glutathione enzymes. The administration of geraniol in diabetic rats promoted a decrease in the concentration of lipid hydroperoxide (HP) and protein carbonyl (PC) and increased the activity of the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) antioxidant enzymes, when compared to animals in the DM group. In conclusion, the administration of geraniol reduced the harmful effects observed in the diabetic condition, through its antidiabetogenic and antioxidant effect.
Diabetes mellitus (DM) is a metabolic disease characterized by persistent hyperglycemia, with disorders in the metabolism of carbohydrates, lipids and proteins, resulting from defects in insulin secretion, insulin action, or both. The use of antioxidants has contributed to improve hyperglycemia and also minimize diabetic complications. Geraniol, a monoterpene, present in the composition of essential oil of various medicinal plants, has oxidant and antihyperglycemic action, being able to contribute in the therapy of this pathology. This study aimed to evaluate the energetic metabolism and oxidative stress in the myocardium of rats with type 1 DM treated with geraniol. 32 male Wistar rats (±250g body weigth), distributed in four experimental groups (n=8): C (normal, control); GE (normal, treated with geraniol); DM (diabetic, untreated); DM-GE (diabetic, treated with geraniol). Experimental type 1 DM was induced by streptozotocin (STZ - 60mg/Kg body weight, i.p., single dose). Animals of the group GE and DM-GE received geraniol (200mg/K/day) by gavage for 30 days and animals of the group C and DM received water by the same procedure. Animals of the group GE and DM-GE received geraniol (200mg/K/day) by gavage for 30 days and animals of the group C and DM received water by the same procedure. During the experimental period, food and water intake were evaluated. After this period the animals, in a 12h fast, were anesthetized and euthanized. Serum samples were collected for glycemia concentration and lipid profile and portions of cardiac tissue for glycogen dosage, triacylglycerols, total proteins, enzymes of energy metabolism and oxidative stress. Results were analyzed by One-way ANOVA followed by Tukey test for comparison of means. The results were considered significant when p<0.05. Decreased in food consumption, water consumption and energy intake (p<0.05), however greater body weight and weight gain in diabetic animals treated with geraniol (DM-GE) compared to untreated diabetic animals (DM). The administration of geraniol in DM-GE also caused a decrease in serum glycemia, cholesterol, triacylglycerols, VLDL-cholesterol and LDL-cholesterol, an increase in serum HDL-cholesterol concentration (DM-GE) when compared to DM group. DM group showed lower cardiac glycogen concentrations in relation to the other groups and the treatment with geraniol increased this parameter (p<0.05). The cardiac concentration of triglycerides was higher (p<0.05) in the DM and DM-GE groups, differing statistically from the other groups. The cardiac activity of both fosfofrutoquinase (PFK) and pyruvate dehydrogenase (PiDH) was lower in the DM group, with an increase in the presence of geraniol. Animals of the DM group showed increased cardiac activity for citrate synthase (CS) and β-hydroxyl CoA dehydrogenase (OHADH) and with the use of geraniol the activity of these enzymes decreased. The activity of NADH-dehydogrenase (NADH-DH), succinate dehydrogenase (SUC-DH) and ATP-synthase were decreased in the animals of the DM group and the use of geraniol reestablished the activity of NADH-DH and ATP-synthase; animals from the GE group had the ATP-synthase activity increased, differing from the other groups. As for the parameters of oxidative stress, no significant differences were observed in the activity of glutathione reduced (GSH) and total glutathione enzymes. The administration of geraniol in diabetic rats promoted a decrease in the concentration of lipid hydroperoxide (HP) and protein carbonyl (PC) and increased the activity of the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) antioxidant enzymes, when compared to animals in the DM group. In conclusion, the administration of geraniol reduced the harmful effects observed in the diabetic condition, through its antidiabetogenic and antioxidant effect.
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Palavras-chave
Geraniol, miocárdio, diabetes mellitus, heart