Salutary effect of NFκB inhibitor and folacin in hyperhomocysteinemia–hyperlipidemia induced vascular dementia

Abstract

Dementia of vascular origin or vascular dementia (VaD) is considered as the second commonest form of dementia after Alzheimer's disease (AD). In the last ten years various researchers have reported a strong association of hyperhomocysteinemia (HHcy), hyperlipidemia (HL) and dementia. This study investigates the salutary effect of natrium diethyl dithio carbamate trihydrate (NDDCT), a nuclear factor-kappaB (NF-κB) inhibitor as well as folacin (Vitamin-B(9)) in HHcy-HL induced VaD. l-methionone was used to induce HHcy-HL and associated VaD. Morris water-maze (MWM) was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Biochemical estimations were performed to assess HHcy (serum homocysteine), HL (serum cholesterol), oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species and brain glutathione), nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity). L-methionine treated animals have shown HHcy-HL, endothelial dysfunction, impairment of learning, memory, reduction in serum nitrite/nitrate levels and brain glutathione (GSH) along with increase in serum and brain thiobarbituric acid reactive species (TBARS), and brain acetylcholinesterase activity. NDDCT, folacin and donepezil (positive control) significantly improved HHcy-HL induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. l-methionine induced HHcy-HL has caused VaD development in rats. NFκ-B inhibitors and folacin may be considered as potential agents for the management of HHcy-HL induced VaD.