Neuroprotective effects of carnitinoid compounds in rodent cellular and in vivo models of mitochondrial complex I dysfunction

Abstract

Rotenone-mediated mitochondrial complex I inhibition was used to model Parkinson’s disease-like syndrome in Lewis rats. Tyrosine hydroxylase immunolabeling demonstrated a decrease in the number of dopaminergic neurons as well as aberrant morphology in surviving neurons. Administration of carnitinoid compounds (synthetic lipoylcarnitine or butyrylcarnitine compounds) reduced dopaminergic neuronal cell loss with characteristic morphology observed in surviving neurons. In a rat primordial hippocampal cell line (H19-7/IGF-IR), rotenone treatment resulted in increased ROS and reduced cellular ATP, while co-treatment with lipoylcarnitine maintained ROS and ATP at control levels. These results illustrate the therapeutic potential of small-molecule carnitinoids in treating neurodegenerative diseases associated with mitochondrial dysfunction.