Effect of wedelolactone and gallic acid on quinolinic acid-induced neurotoxicity and impaired motor function: significance to sporadic amyotrophic lateral sclerosis

• Published in: Neurotoxicology (Park Forest South) Vol. 68; pp. 1 - 12
• Main Authors: S, Maya, T, Prakash, Goli, Divakar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2018; Elsevier BV
• Subjects: Amyotrophic lateral sclerosis; Antioxidants; Apoptosis; Brain; Calpain; Cascades; Caspase; Caspase-3; Catalase; Cerebellum; Cytotoxicity; Degeneration; Excitotoxicity; Gallic acid; Glutathione; Glutathione peroxidase; Growth factors; Inflammation; Insulin-like growth factor I; Interleukin 6; Learning; Lipid peroxidation; Lipids; Memory; Motor ability; Neostriatum; Neurodegeneration; Neurogenesis; Neurotoxicity; Peroxidase; Peroxidation; Prevention; Quinolinic acid; Rats; Spinal cord; Toxicity; Tryptophan; Vascular endothelial growth factor; Wedelolactone; Wedelolactone; Amyotrophic lateral sclerosis; Neurotoxicity; Quinolinic acid; Gallic acid; Neurodegeneration
• ISSN: 0161-813X; 1872-9711; 1872-9711
• DOI: 10.1016/j.neuro.2018.06.015

•Quinolinic acid is well known endogenous neuroactive metabolite of tryptophan degradation pathway.•Quinolinic acid causes neurotoxicity and impairment in motor function and motor learning memory.•Wedelolactone and Gallic acid were improved the motor function and motor learning ability in the rats.•Wedelolactone and Gallic acid are capable to act through various pathways and can reduce reverse the toxic events triggered by quinolinic acid. Quinolinic acid (QUIN) is a well-known neuroactive metabolite of tryptophan degradation pathway or kynurenine pathway. The QUIN is involved in the development of several toxic cascades which leads to the neuronal degeneration processes. The QUIN-induced toxicity is also responsible for the impairment of the motor function and motor learning ability. This study seeks to investigate the several mechanisms which are involved in the intrastriatal administration of QUIN-induced neurodegeneration and the neuroprotective effects of wedelolactone (WL) and gallic acid (GA) over QUIN-induced toxicity. The Wistar rats were used for the study and conducted behavioral model to evaluate the effects of WL (100 & 200 mg/kg) and GA (100 & 200 mg/kg) on impaired motor function and motor learning ability. We also assessed the effects of WL and GA on the antioxidant profile, cytotoxicity, apoptosis, excitotoxicity, inflammatory cascades, and on growth factors which helps in neurogenesis. The compounds effectively improved the motor function, motor learning memory in the rats. Similarly, enhanced the activity of Glutathione peroxidase, SOD, catalase, and declined the lipid peroxidation and nitrite production in the brain. The treatment with WL and GA lowered the activities of LDH, m-calpain, and caspase-3. The reports strongly support that both compounds are useful in the prevention of glutamate excitotoxicity induced by QUIN. The NAA, IGF-1, and VEGF levels in the brain were improved after treatment with WL and GA. The neuroprotective effects of WL and GA further proved through the anti-inflammatory effects. The compounds significantly down-regulated the expression of TNF-α, IL-6, and IL-β in the brain. Immunohistochemical analysis shows that the WL and GA reduced the expression of NF-κB. The histopathological studies for cerebellum, hippocampus, striatum, and spinal cord confirms the toxic effects of QUIN and neuroprotective effects of WL and GA. The results suggest that WL and GA could ameliorate the toxic events triggered by QUIN and might be effective in the prevention and progression of several cascades which lead to the development of sALS.