Pelargonidin as an Attenuator of Neuronal Mitochondrial Dysfunction: An in Vivo Study

Abstract

Targeting the neuronal mitochondria as a possible intervention to guard against neurodegenerative disorders' progression has been investigated in the current work via the administration of Pelargonidin (PEL) to rats intoxicated by the mitochondrial toxin Reserpine. The main criteria for choosing pelargonidin (PEL) were its reported poly (ADP-ribose) polymerase (PARP)-inhibitor, antioxidant, anti-apoptotic and anti-inflammatory activities. Male rats were randomized into four experimental groups; normal control, reserpinized to induce mitochondrial failure, standard PARP-1-inhibitor 1,5-isoquinolinediol (DIQ)-treated reserpinized, and PEL-treated reserpinized . PEL significantly restored brain glutathione (GSH) with a reduction in nitric oxide contents as compared to reserpine-challenged group. Meanwhile, it improved the neuronal mitochondrial function by the elevation of complex I activity associated with a low ADP/ATP ratio. Likely, through its anti-inflammatory effect, PEL reduced the elevation of serum interlukine-1ß level and inhibited serum lactate dehydrogenase (LDH) activity. These findings were aligned with the reduced expressions of cleaved PARP and cleaved caspase-3 proteins, indicating PEL suppressive effect to the intrinsic apoptotic pathway. Those biochemical findings were confirmed through comparable histopathological tissue examination among the experimental groups. In conclusion, PEL is a promising candidate for the future use in management of mitochondria-associated neuronal complications via controlling the ongoing inflammatory and degeneration cascades.