TNF-α antagonist alleviates muscular layer enlargement but does not prevent myenteric neuronal loss in the colon of streptozotocin-induced diabetic rats.

BACKGROUND

this study aimed to examine the impact of a TNF-α antagonist on markers of neuronal death, the total number of myenteric neurons, and the volume of each colonic layer in diabetic rats.

METHODS

thirty male rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. Diabetes was induced using streptozotocin and nicotinamide. The DE group received twice-weekly injections of etanercept. Immunohistochemistry staining and western blotting detected activated caspase-3, Gasdermin D, and phosphorylated-MLKL. Stereological methods were performed in colon sections stained with Toluidine-blue to estimate the total number of neurons in the colonic myenteric plexus and the colonic layer volume.

RESULTS

immunohistochemistry showed etanercept reduced expression of apoptosis and pyroptosis markers, but not necroptosis, in the myenteric plexus of the colon in diabetic rats. Diabetic rats exhibited a lower total number of neurons in the colonic myenteric ganglions, and etanercept did not prevent this neuronal loss. Furthermore, colonic layer enlargement was observed in diabetic rats, with only the muscular layer hypertrophy being prevented by etanercept administration.

CONCLUSIONS

the TNF-α antagonist did not prevent neuronal loss in the colonic myenteric plexus; it partially inhibited colonic muscular layer enlargement in diabetic rats.