Abstract
Background
Targeting the neuronal mitochondria as a possible intervention to guard against neurodegenerative disorder 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 PEL were its reported antioxidant, anti-apoptotic and anti-inflammatory activities.
Methods
Male albino Wistar rats were randomized into five experimental groups; normal control, reserpinized to induce mitochondrial failure, standard PARP-1-inhibitor 1,5-isoquinolinediol (DIQ)-treated reserpinized, PEL-treated reserpinized, and GSK-3β inhibitor (AR-A 014418) -treated reserpinized.
Results
PEL administration reversed the reserpine-induced abnormal behaviors marked by decreased catalepsy time. In addition, PEL restored brain glutathione with a reduction in nitric oxide content as compared to the reserpine-challenged group. Meanwhile, it improved 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 interleukin-1ß level and inhibited serum lactate dehydrogenase activity. These findings are aligned with the reduced expression of cleaved PARP and cleaved caspase-3 proteins, indicating PEL’s suppressive effect on the intrinsic apoptotic pathway. Those biochemical findings were confirmed through comparable histopathological tissue examination among the experimental groups.
Conclusions
In conclusion, PEL is a promising candidate for future use in the management of mitochondria-associated neuronal complications via controlling the ongoing inflammatory and degeneration cascades.
Acknowledgements
The preliminary version of this work was posted on the Research Square server as a preprint (Rashed et al. Citation2021).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
Underlying data Open Science Framework: Neuronal mitochondrial dysfunction https://osf.io/s2ykm/?view_only=ea084d1f32104df8adc2824e62850dfc