Neuroprotective Effects of Selected Natural Ergogenic Antioxidant Poly(ADP-Ribose)Polymerase-1 Inhibitors Against Experimentally Induced Alzheimer’s Disease in Aged Rats

Introduction: Oxidative stress (OS), inflammation, and ultimate irreversible membrane molecular mitochondrial damages and genome instabilities are implicated in aging and age-related progressive neurodegenerative diseases (NDDs), such as Parkinsonism, Senile Dementia and Alzheimer’s Disease (AD). α-Lipoic acid, acetyl-L-carnitine, coenzyme-Q, and niacin are iron-chelating antioxidant ergogenic-aids which play a pivotal role and exert cytoprotective effects against innumerable neurodegenerative diseases (NDDs). The ICV injection of streptozotocin (STZ) leads to neurodegeneration. This present study is used to estimate the neuroprotective effect of selected natural poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors on the biomarkers of OS and genome instability, inflammation, and DNA repair enzymes in STZ-induced neurotoxicity.

Materials and Methods: Male aged albino rats (24 months old, 350 gm body wt) were pretreated with α-lipoic acid and/or, acetyl-L-carnitine, nicotinamide, and coenzyme-Q (started 3 days prior to STZ) (100mg/kg b.wt, i.p for 21 days), followed by bilateral i.c.v injection with the DNA-destabilizing genotoxin STZ (100mg/kg b.wt). At the end of the 21 days, the hippocampus was dissected-out, and relevant biochemical parameters were estimated.

Results: The combined application of ergogenic antioxidants mitigated the toxic onslaught of SZN-induced neurotoxicity and exerted neuroprotection by significantly reducing MDA, 8-OHdG, AChE activity, IL-6, TNF-α, XO, NOS, the augmentation of antioxidants, ATP, DNA and NTs, and the modulation of PARP-1. PARP-1 expression was found to increase exponentially with the severity of OS and was found to decrease significantly with decreased OS.

Conclusion: The combined application of ergogenic antioxidants, such as α-Lipoic acid, acetyl-L-carnitine, coenzyme-Q, and/or niacin, will be effective in the treatment and/or management of progressive NDDS (such as AD).