Synthesis, characterization and efficacy of mitochondrial targeted delivery of TPP-curcumin in rotenone-induced toxicity.

Background: Mitochondrial impairments due to free radicals are implicated in a wide range of neurotoxicological alterations. Curcumin, an active ingredient of turmeric has shown protective efficacy against oxidative damage due to its strong antioxidant potential, but its efficiency is restricted due to low bioavailability in the mitochondria. In view of this, we have synthesized mitochondria-targeted curcumin (MTC) with an aim to investigate its efficacy against rotenone-induced oxidative damage in mice and isolated mitochondria.

Methods: MTC was synthesized by attaching the triphenylphosphonium cation (TPP) as a cationic carrier to the curcumin to assess its protective efficacy in rotenone-induced in-vitro and in-vivo toxicity in mice.

Results: In-vitro treatment of rotenone in isolated mitochondria caused a significant increase in lipid peroxidation (2.74 fold, 3.62 fold), protein carbonyl contents (2.62 fold, 1.81 fold), and decrease in levels of reduced glutathione (2.02 fold, 1.70 fold) as compared to control. Pre-treatment of curcumin and MTC along with rotenone in the isolated mitochondria significantly reduce the oxidative stress as compared to those treated with rotenone alone. Rotenone treatment in mice significantly increased lipid peroxidation (2.02 fold) and decreased the levels of reduced glutathione (2.99 fold), superoxide dismutase (2.09 fold) and catalase (3.60 fold) in the liver as compared to controls. Co-treatment of curcumin and MTC along with rotenone significantly reduced lipid peroxidation (1.26 fold, 1.76 fold) and increased the levels of reduced glutathione (1.60 fold, 2.43 fold), superoxide dismutase (1.45 fold, 1.99 fold) and catalase (2.32 fold, 2.90 fold) as compared to those treated with rotenone alone.

Conclusion: The results of the present study indicate that the protective efficacy of MTC against rotenone-induced oxidative damage was more promising than curcumin in both in-vitro and in-vivo system which indicates the enhanced bioavailability of MTC. Graphical abstract Effect of mitochondrial targeted delivery of TPP-curcumin in rotenone-induced toxicity.