Lung-based evaluation of oxidative stress and inflammation in an established STZ Sprague-Dawley rat model

Abstract

Streptozotocin (STZ) is a commonly used compound for the induction of type 2 diabetes mellitus (T2DM) in animal models, through its cytotoxic effect on pancreatic cells. However, its acute effects on non-pancreatic tissues like the lungs are not well understood. This study aimed to examine the histopathological impact of STZ on the lungs of male Sprague-Dawley rats. The rats were divided into two groups: a control group on a normal diet and an experimental group receiving a high-fat diet and 10% sucrose water for 8 weeks, followed by an STZ injection (30 mg/kg body weight). All the rats were terminated 9 days after STZ administration, and lung samples were collected for analyses using light microscopy, transmission electron microscopy (TEM), immunohistochemistry (IHC) and confocal fluorescence laser scanning microscopy (CFLSM). Light microscopy revealed alterations in lung structure including thickening of alveolar septa, narrowing of alveoli, and inflammatory infiltrates in the STZ group. TEM revealed mitochondrial damage in type 2 pneumocytes, including membrane fragmentation, cristae loss, and formation of mitochondrial-derived vesicles. Immunohistochemistry results indicated the presence of both oxidative stress (OS) using markers 8-Hydroxyguanosine and nitrotyrosine and inflammation using markers TNF-α and IL-6 in the experimental groups. Confocal microscopy revealed a significantly higher expression of myeloperoxidase, neutrophil elastase, and citrullinated histone 3 in the STZ group compared to controls. These findings suggest that STZ induces considerable lung damage, emphasizing the need to consider lung toxicity in studies involving STZ.