Indirubin prevents structural damage to chicken lungs and trachea caused by <i>Mycoplasma gallisepticum</i> infection through attenuating oxidative stress and apoptosis

1. This study evaluated the mechanism of action of indirubin in alleviating the structural damage induced by <i>Mycoplasma gallisepticum</i> (MG) in the lungs and trachea.2. A total of 250 one-day-old white leghorn chickens, specific-pathogen-free were divided into six treatment groups, including (A) indirubin high concentration treatment group (50 mg/kg; IHC); (B) indirubin medium concentration treatment group (25 mg/kg; IMC); (C) indirubin low concentration treatment group (12.5 mg/kg; ILC); (D) tylosin control group (0.5 g/l); (E) control group (CON) and (F) challenge model group (MG).3. Results from antioxidant activity analysis demonstrated that indirubin treatment significantly decreased the amount of MG-mediated oxidative stress in the lungs of chickens. Histopathological examination revealed abnormal morphological signs and cell damage in MG birds. This included lung lymphocytic infiltration, overlapping nuclear debris and inflammatory cell infiltration. In addition, ultrastructural examination revealed signs of apoptosis in the lungs. However, indirubin treatment partially relieved these abnormal morphological changes.4. The TUNEL analysis showed extensive apoptosis in the lungs of the model group compared to the control and positive drug control group. Apoptosis-related protein expression levels were significantly upregulated in the model group, which confirmed the phenomena of apoptosis induced by MG. The indirubin treatment significantly reduced apoptosis in the lungs and trachea compared to the model group. Meanwhile, the effect of MG challenge was reduced in the lungs by indirubin in a dose-dependent manner.5. These results showed that the inhibition of oxidative stress and apoptosis by indirubin contributed to its therapeutic effects against MG infection.