Avaliação do efeito da melatonina no sinal insulínico e estresse oxidativo em ratos com periodontite apical submetidos à inalação passiva de tabaco
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Data
2023-02-24
Autores
Bravo, Lara Teschi [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A periodontite apical (PA) e o tabagismo podem estar associados com a síndrome metabólica, diabetes mellitus, alteração do sinal insulínico e resistência insulínica (RI). A melatonina (MEL) é um hormônio com propriedades antioxidantes, anti-inflamatórias e com participação na remodelação óssea. Estudos anteriores mostram que a MEL melhora a sensibilidade à insulina e sinalização insulínica no músculo esquelético de ratos com PA. Nesse contexto, hipotetizamos que as alterações metabólicas em ratos com PA sejam mais pronunciadas com à inalação passiva de tabaco e a administração de MEL possa prevenir ou diminuir estas alterações. O objetivo deste trabalho foi avaliar a sensibilidade à insulina, estresse oxidativo e via de sinalização insulínica no músculo esquelético de ratos adultos com PA submetidos à inalação passiva do tabaco. Foram utilizados 128 ratos Wistar com 60 dias de idade distribuídos em 8 grupos: controle (CN); ratos tabagistas (T); ratos com PA (PA); ratos tabagistas com PA (T+PA); controle tratados com MEL (CN+MEL); ratos tabagistas tratados com MEL (T+MEL); ratos com PA tratados com MEL (PA+MEL); ratos tabagistas com PA tratados com MEL (T+PA+MEL). Os grupos tabagistas receberam à inalação passiva da fumaça do cigarro durante 50 dias, sendo que no 20º dia, os grupos PA foram submetidos à indução da periodontite apical, com auxílio de uma broca em aço carbono em primeiros e segundos molares superiores e inferiores do lado direito. Ademais, os animais dos grupos MEL foram suplementados com melatonina (5 mg/Kg, via oral por meio de gavagem) do 20º dia até 50º dia experimental. Foram analisados glicemia, insulinemia, sensibilidade à insulina (HOMA-IR), grau defosforilação em tirosina da pp185 e estresse oxidativo (superóxido dismutase - SOD e substâncias reativas ao ácido tiobarbitúrico - TBARS) no músculo gastrocnêmio (MG). A normalidade dos dados foi avaliada pelo teste de Shapiro-Wilk. Em função dos resultados do teste de normalidade foram utilizados testes paramétricos para comparar glicemia, insulinemia, sensibilidade à insulina, grau de fosforilação em tirosina da pp185 e estresse oxidativo no MG entre os grupos, com nível de significância de 5%. Os resultados do presente estudo demonstram que os grupos PA, T e T+PA apresentaram aumento da RI quando comparados ao grupo CN. Além do mais, o grupo T+PA apresentou menor sensibilidade à insulina quando comparado aos grupos T e PA, sugerindo que a associação das variáveis, tabaco e periodontite apical, promove alteração exacerbada neste parâmetro metabólico em relação aos grupos analisados isoladamente. Interessantemente, a administração de MEL em animais com tabaco (grupos T+MEL), periodontite apical (PA+MEL) e a associação destas variáveis (grupo T+PA+MEL) foi capaz de melhorar a sensibilidade à insulina. Em relação ao peso e ingestão alimentar, não foram encontradas diferenças significativas entre os grupos. Houve prejuízo na transdução da etapa inicial do sinal insulínico nos grupos PA, T e T+PA. A MEL promoveu melhora neste parâmetro somente no grupo de animais com PA (PA+MEL). Além disso, não houve diferença estatística na atividade da defesa antioxidante (SOD) entre os grupos. A administração de MEL em animais tabagistas (T+MEL) ou PA (PA+MEL) promoveu diminuição no dano lipídico (TBARS). Pode-se concluir que ações da PA e do tabagismo se relacionam com o aumento da RI e a associação destes fatores (grupo T+PA) exacerbou os parâmetros sistêmicos correlacionados com a insulinemia e HOMA-IR. Em contrapartida, a suplementação da MEL foi capaz de reverter a RI (grupos PA+MEL, T+MEL e PA+T+MEL) e o dano lipídico (TBARS, grupos T+MEL e PA+MEL), demonstrando suas ações anti-inflamatórias e antioxidantes.
Apical periodontitis (AP) and smoking may be associated with metabolic syndrome, diabetes mellitus, altered insulin signal and insulin resistance (IR). Melatonin (MEL) is a hormone with antioxidant, anti-inflammatory properties and participation in bone remodeling. Previous studies show that MEL improves insulin sensitivity and insulin signaling in skeletal muscle of rats with AP. In this context, we hypothesized that the metabolic alterations in rats with AP are more pronounced with passive inhalation of tobacco and the administration of MEL can prevent or reduce these alterations. The objective of this work was to evaluate insulin sensitivity, oxidative stress and insulin signaling pathway in the skeletal muscle of adult rats with AP submitted to passive inhalation of tobacco. 128 Wistar rats, 60 days old, were divided into 8 groups: control (CN); smoking rats (T); rats with AP (AP); smoking rats with AP (T+AP); control treated with MEL (CN+MEL); smoking rats treated with MEL (T+MEL); mice with AP treated with MEL (AP+MEL); smoking rats with AP treated with MEL (T+AP+MEL). The smokers groups received passive inhalation of cigarette smoke for 50 days, and on the 20th day, the AP groups were submitted to the induction of apical periodontitis, with the aid of a carbon steel drill in the upper and lower first and second molars on the lateral side right. Furthermore, the animals in the MEL groups were supplemented with melatonin (5 mg/Kg, orally through gavage) from the 20th to the 50th experimental day. Glycemia, insulinemia, insulin sensitivity (HOMA-IR), degree of pp185 tyrosine phosphorylation and oxidative stress (superoxide dismutase - SOD and thiobarbituric acid reactive substances - TBARS) were analyzed in the gastrocnemius muscle (MG). Data normality was assessed using the Shapiro-Wilk test. Based on the results of the normality test, parametric tests were used to compare glycemia, insulinemia, insulin sensitivity, degree of pp185 tyrosine phosphorylation and oxidative stress in the MG between groups, with a significance level of 5%. The results of the present study demonstrated that the AP, T and T+AP groups showed an increase in IR when compared to the CN group. Moreover, the T+PA group presented lower insulin sensitivity when compared to groups T and AP, suggesting that the association of the variables, tobacco and apical periodontitis, promotes exacerbated change in this metabolic parameter in relation to the groups analyzed separately. Interestingly, the administration of MEL in animals with tobacco (T+MEL groups), apical periodontitis (AP+MEL) and the association of these variables (T+AP+MEL group) was able to improve insulin sensitivity. Regarding weight and food intake, no significant differences were found between groups. There was impairment in the transduction of the initial stage of the insulin signal in the AP, T and T+AP groups. MEL promoted improvement in this parameter only in the group of animals with AP (AP+MEL). Furthermore, there was no statistical difference in antioxidant defense activity (SOD) between groups. The administration of MEL in smoking animals (T+MEL) or AP (AP+MEL) promoted a decrease in lipid damage (TBARS). It can be concluded that AP and smoking actions are related to increased IR and the association of these factors (T+AP group) exacerbated the systemic parameters correlated with insulinemia and HOMA-IR. In contrast, MEL supplementation was able to reverse IR (AP+MEL, T+MEL and T+ AP+MEL groups) and lipid damage (TBARS, T+MEL and AP+MEL groups), demonstrating its anti-inflammatory actions and antioxidants.
Apical periodontitis (AP) and smoking may be associated with metabolic syndrome, diabetes mellitus, altered insulin signal and insulin resistance (IR). Melatonin (MEL) is a hormone with antioxidant, anti-inflammatory properties and participation in bone remodeling. Previous studies show that MEL improves insulin sensitivity and insulin signaling in skeletal muscle of rats with AP. In this context, we hypothesized that the metabolic alterations in rats with AP are more pronounced with passive inhalation of tobacco and the administration of MEL can prevent or reduce these alterations. The objective of this work was to evaluate insulin sensitivity, oxidative stress and insulin signaling pathway in the skeletal muscle of adult rats with AP submitted to passive inhalation of tobacco. 128 Wistar rats, 60 days old, were divided into 8 groups: control (CN); smoking rats (T); rats with AP (AP); smoking rats with AP (T+AP); control treated with MEL (CN+MEL); smoking rats treated with MEL (T+MEL); mice with AP treated with MEL (AP+MEL); smoking rats with AP treated with MEL (T+AP+MEL). The smokers groups received passive inhalation of cigarette smoke for 50 days, and on the 20th day, the AP groups were submitted to the induction of apical periodontitis, with the aid of a carbon steel drill in the upper and lower first and second molars on the lateral side right. Furthermore, the animals in the MEL groups were supplemented with melatonin (5 mg/Kg, orally through gavage) from the 20th to the 50th experimental day. Glycemia, insulinemia, insulin sensitivity (HOMA-IR), degree of pp185 tyrosine phosphorylation and oxidative stress (superoxide dismutase - SOD and thiobarbituric acid reactive substances - TBARS) were analyzed in the gastrocnemius muscle (MG). Data normality was assessed using the Shapiro-Wilk test. Based on the results of the normality test, parametric tests were used to compare glycemia, insulinemia, insulin sensitivity, degree of pp185 tyrosine phosphorylation and oxidative stress in the MG between groups, with a significance level of 5%. The results of the present study demonstrated that the AP, T and T+AP groups showed an increase in IR when compared to the CN group. Moreover, the T+PA group presented lower insulin sensitivity when compared to groups T and AP, suggesting that the association of the variables, tobacco and apical periodontitis, promotes exacerbated change in this metabolic parameter in relation to the groups analyzed separately. Interestingly, the administration of MEL in animals with tobacco (T+MEL groups), apical periodontitis (AP+MEL) and the association of these variables (T+AP+MEL group) was able to improve insulin sensitivity. Regarding weight and food intake, no significant differences were found between groups. There was impairment in the transduction of the initial stage of the insulin signal in the AP, T and T+AP groups. MEL promoted improvement in this parameter only in the group of animals with AP (AP+MEL). Furthermore, there was no statistical difference in antioxidant defense activity (SOD) between groups. The administration of MEL in smoking animals (T+MEL) or AP (AP+MEL) promoted a decrease in lipid damage (TBARS). It can be concluded that AP and smoking actions are related to increased IR and the association of these factors (T+AP group) exacerbated the systemic parameters correlated with insulinemia and HOMA-IR. In contrast, MEL supplementation was able to reverse IR (AP+MEL, T+MEL and T+ AP+MEL groups) and lipid damage (TBARS, T+MEL and AP+MEL groups), demonstrating its anti-inflammatory actions and antioxidants.
Descrição
Palavras-chave
Melatonina, Fumo, Periodontite periapical, Resistência à insulina, Estresse oxidativo, Oxidative stress