A neuroprotective dose of trehalose is harmless to metabolic organs: comprehensive histopathological analysis of liver, pancreas, and kidney.

Background: Trehalose is a non-reducing disaccharide synthesized by lower organisms. It has recently received special attention because of its neuroprotective properties by stimulating autophagy in Parkinson's disease (PD) models. Therefore, evaluating whether trehalose affects metabolic organs is vital to determine its neurotherapeutic safety.

Methods: We validated the trehalose neuroprotective dosage in a PD model induced with intraperitoneal paraquat administration twice weekly for 7 weeks. One week before paraquat administration, mice were treated with trehalose in the drinking water and continued along with paraquat treatment. Histological and morphometrical analyses were conducted on the organs involved in trehalose metabolism, including the liver, pancreas, and kidney.

Results: Paraquat-induced dopaminergic neuronal loss was significantly decreased by trehalose. After trehalose treatment, the liver morphology, the mononucleated/binucleated hepatocytes percentage, and sinusoidal diameter remained unchanged in each liver lobes. Endocrine and exocrine pancreas's histology was not affected, nor was any fibrotic process observed. The islet of Langerhans's structure was preserved when analyzing the area, the largest and smallest diameter, and circularity. Renal morphology remained undamaged, and no changes were identified within the glomerular basement membrane. The renal corpuscle structure did not suffer alterations in the Bowman's space, area, diameter, circularity, perimeter, and cellularity. Besides, the renal tubular structures's luminal area and internal and external diameter were preserved.

Conclusion: Our study demonstrates that systemic trehalose administration preserved the typical histological architecture of the organs involved in its metabolism, supporting its safety as a potential neuroprotective agent.