Conclusions
Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.
Methods
In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels.
Results
The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT-1/PPAR-gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.