Investigation of the effect of melatonin on lung tissue damage in Type- 2 diabetic male rats via Nrf2/TLR4 axis

Abstract

So far, many studies have shown the effectiveness of melatonin in animal models of diabetes and chronic respiratory system diseases. However, the main mechanism of its therapeutic effects in reducing the pulmonary complications of diabetes and chronic lung diseases has not been fully understood. Therefore, in this study, the effect of melatonin on lung tissue damage in male rats with type 2 diabetes was investigated through the Nrf2/TLR4 axis. Methods In this study, 24 adult male rats with an approximate weight of 180 to 210 grams were randomly divided into 3 groups of 8 including the control group, the diabetes group, and the diabetes + melatonin group. In order to induce type 2 diabetes, the animals will receive a high-fat diet for four weeks. and at the end of the fourth week, streptozotocin (35mg/kg) was injected intraperitoneally. The high-fat diet was continued for 8 weeks after the induction of diabetes in the animals. In the group receiving melatonin, melatonin was injected intraperitoneally twice a week with a dose of 3 mg/kg along with the high-fat diet for 8 weeks after the induction of diabetes. At the end of the twelfth week, the animals were killed by injecting a high dose of ketamine and xylazine, and their lung tissue was removed for the desired investigations. Real Time-PCR was used to express genes related to Nrf2/TLR4. Hematoxylin and Vosin dye were used to examine pathological changes.

Results Our results showed that the induction of type 2 diabetes can increase the pathological changes, decrease the expression of Nrf2 and increase the expression of TLR4, MYD88, TRIF and IRAK-1 in the lung tissue of diabetic animals compared to the control group. Intraperitoneal injection of melatonin reduced lung tissue damage.