Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat

Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50 mg/kg) was injected intraperitonealy once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 μmol/μl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24 h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity.

Research highlights►Homocysteine (Hcy) could induce oxidative stress on the rat brain and induced lipid peroxidation in the rat's hippocampal tissue significantly ►Curcumin at low, middle and high doses inhibited hippocampus lipid peroxidation with Hcy ►Hcy significantly decreased cell density in Dentate Gyrus layer of hippocampus ►Curcumin improved cell density in Dentate Gyrus layer of hippocampus in Hcy-treated animals ►Hcy decreased latency time in passive avoidance leaning test that indicated the impairment of leaning and memory by Hcy ►Curcumin significantly improved Hcy-induced memory impairment ►Co-administration of Hcy with polyphenolic antioxidant, Curcumin protected neuronal cells against Hcy toxicity ►Two markers of lipid peroxidation including Malondialdehyde(MDA) and Super Oxide Anion (SOA) were detected by colorimetric method in the hippocampal homogenate of rat ►Histopathological analysis also showed the toxicity of Hcy on hippocampus cell density in the different layers of the rat's hippocampus