Alterações pulmonares em um modelo de diabetes mellitus em ratos: o efeito da terapia antioxidante

Abstract

Objective: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD) has on such alterations. Methods: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each): control; SOD-only (without DM but treated with SOD); IDM-only (with streptozotocininduced DM but untreated); and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were evaluated over a 60-day period, day 0 being defined as the day on which the streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was administered for the last 7 days of that period. At the end of the study period, samples of lung tissue were collected for histopathological analysis, evaluation of tissue oxidative stress, and assessment of DNA damage. Results: There were no significant differences among the groups regarding DNA damage. In the IDM-only group, there was a significant increase in the extracellular matrix and significantly greater hyperplasia of the capillary endothelium than in the SOD-only and control groups. In addition, there were significant changes in type II pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only group. However, in the IDM+SOD group, there was a reduction in the extracellular matrix, as well as normalization of the capillary endothelium and of the type II pneumocytes. Conclusions: Exogenous SOD can reverse changes in the lungs of animals with induced DM.Keywords: Diabetes mellitus, experimental; Oxidative stress; Lung; DNA damage. ResumoObjetivo: Avaliar as alterações estruturais no pulmão de ratos com diabetes mellitus (DM) através da quantificação do estresse oxidativo e do dano ao DNA, assim como determinar os efeitos de superóxido dismutase (SOD) exógena nessas alterações. Métodos: Estudo experimental controlado com 40 ratos Wistar, divididos em quatro grupos (10 animais cada): grupo controle, grupo SOD (sem DM e tratados com SOD), grupo DM (com DM induzido por estreptozotocina), e grupo DM+SOD (com DM induzido por estreptozotocina e tratados com SOD). Os animais foram avaliados por um período de 60 dias, iniciado a partir do dia em que os animais com diabetes induzido por estreptozotocina apresentaram glicemia > 250 mg/dL. Nos últimos 7 dias do período, os animais nos grupos tratados receberam SOD. Ao final do tempo de estudo, amostras de tecido pulmonar foram coletadas para análise histopatológica e avaliação do estresse oxidativo e do dano ao DNA. Resultados: Não houve diferenças significativas entre os grupos em relação ao dano ao DNA. Houve um aumento significativo na matriz extracelular e hiperplasia do endotélio capilar no grupo DM quando comparado com os grupos controle e SOD. Também houve mudanças significativas em pneumócitos tipo II e macrófagos intravasculares, sugerindo um processo inflamatório no grupo DM. Entretanto, uma redução na matriz extracelular, endotélio cap...

A survey of recently published cardiovascular, hematological and pneumological original articles in the Brazilian scientific press

“…presenting low morbidity and no mortality at a referral facility for pediatric thoracic surgery. Forgiarini et al108 evaluated structural alterations of the lung in rats with diabetes mellitus, by quantifying oxidative stress and DNA damage; they alos determined the effects that exogenous superoxide dismutase has on such alterations and conclude that exogenous SOD can reverse changes in the lungs of animals with induced diabetes mellitus. Maranhao et al109 propose a new classification criterion for the differentiation between pleural exudates and transudates quantifying total proteins in pleural fluid (TP-PF) and lactate dehydrogenase in pleural fluid (LDH-PF) exclusively; they also compare this new criterion with the classical criterion in terms of diagnostic yield.…”

Type 2 Diabetes Mellitus Provokes Rat Immune Cells Recruitment into the Pulmonary Niche by Up-regulation of Endothelial Adhesion Molecules

“…Along with these statements, the existence of large contents of collagen and elastin fibers predisposes pulmonary tissue to diabetic changes 3 . Previous analysis of the histological slides revealed an increase in the extracellular matrix, as evidenced by the presence of fibrosis, increase thickness of the alveolar-capillary membrane, hyperplasia of the capillary endothelium in the lung tissue of STZ-induced diabetic animal models 15 . Recent data pointed out that the combination of high-fat diets and STZ in rats could induce chronic diabetic disorders that are appropriately applicable to human counterpart 26,27 .…”

“…Therefore, it is highly recommended to measure the extent of pulmonary ECs involvement during the chronic hyperglycemic condition. Calling attention, the majority of animal studies only explored the detrimental effects of diabetic condition induced STZ on pulmonary tissue which is not completely comparable to the T2D in in vivo condition 14,15 . As expected, the direction and recruitment of immune cells toward the pulmonary niche are mediated by the close interaction of immune cells with ECs 16,17 .…”

Potential Impact of Diabetes and Obesity on Alveolar Type 2 (AT2)-Lipofibroblast (LIF) Interactions After COVID-19 Infection

“…Hyperglycemia can induce oxidative stress, resulting in damage to the lipids, proteins and DNA. Experiments showed that in diabetic lung, content of malondialdehyde (MDA) was significantly increased, but the activity of superoxide dismutase (SOD), one of the key antioxidant enzymes, was decreased ( Forgiarini Junior et al, 2010 ; Zhang et al, 2015 ). Hyperglycemia can induce different abnormalities in the lung, and vascular endothelial cell that can provoke virus-related damage ( Goldman, 2003 ).…”

“…DM through different mechanisms including mitochondrial dysfunction, polyol pathway, and AGEs formation can cause cell damage and induce oxidative stress and inflammation ( Figure 1 ; Zheng et al, 2017 ). DM can affect SOD, CAT, and GSH enzymatic activities and facilitate ROS production ( Forgiarini Junior et al, 2010 ). DM can induce inflammation through activation of the NF-κB pathway ( Baker et al, 2011 ).…”