The Potential Effect of Caffeine and Nicotine Co-administration against Aluminum-induced Alzheimer's disease in Rats

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss. Caffeine and nicotine are the most commonly co-used psycho stimulants. Caffeine is one of the major contributors to the dietary antioxidants which prevent oxidative damage and may reduce the risk of chronic neurodegenerative diseases. Nicotine has the ability to decrease level of reactive oxygen species (ROS) in the hippocampus and suggested to attenuate the impairment of memory associated with AD. The study aimed to evaluate the influence of caffeine and nicotine co-administration against aluminium-induced neurotoxicity that mimics AD in rats. Five groups of rats were used and received daily for five weeks: Saline for control, aluminium chloride (AlCl 3 ) (70 mg/kg, IP) for AD mimic group, while treated groups received together with AlCl 3 , either Caffeine (5mg/kg, IP), Nicotine (1 mg/kg, SC) or their combination. Three behavioral experiments were performed: Forced Swimming Test (FST), Morris Water Maze (MWM) task and Conditioned-Avoidance and Learning (CAL) test. Histo pathological changes in the brain and biochemical changes in Acetyl cholinesterase (AchE) as well as oxidative parameters; malon dialdehyde (MDA), superoxide dismutase (SOD), total anti oxidane capacity (TAC) were also evaluated for all groups. Results of the behavioral tests showed that caffeine and nicotine co-administration had more pronounced protecting effect from learning and memory impairment induced by AlCl 3 than each one alone. Caffeine and nicotine co-administration also prevent neuronal degeneration in the hippocampus and the eosinophilic plagues in the striatum induced by AlCl 3 while nicotine alone still showed mild gliosis in striatum. The marked protection of caffeine and nicotine co-administration confirmed also by the significant increase in TAC and SOD and decrease in MDA and AchE in brain tissue. In conclusion, co-administration of caffeine and nicotine can reduce the risk of neuronal degeneration in the hippocampus and attenuate the impairment of learning and memory associated with AD.

Risk Factors in Induction and Progression of Alzheimer’s Disease: Impacton Protection and Disease-Modifying Factors

“…For example, EGCG is effective in minimizing the hazards of aluminum-induced AD in rats; however the combined therapy of Epigallocatechin-3-gallate (EGCG) and coenzyme Q10 (CoQ10) or EGCG and vitamin E and selenium has more pronounced protective effects than EGCG alone [4, 24,63]. Moreover, coadministration of moderate doses of both caffeine and nicotine can reduce the risk of neuronal degeneration and attenuate the impairment of memory than each of them alone [64]. In addition, the deleterious effect of stress on the brain can be also counteracted by using EGCG together with Diazepam [23].…”

Effects of Fermented Coffee Extracts on Spatial Cognition and Memory of Alzheimer’s Disease Induced Rats

“…The AD induced group, experienced gradual loss of navigation ability, where the rats instead of reaching for the food pellet, it tried returning back to the start area or spent prolonged time in the arm region. AlCl 3, which was injected to induce Alzheimer's disease result in free radical production, giving rise to cognitive decline and difficulty with task response in AD induced rats [33,34]. Moreover, impairment of learning ability and spatial memory indicates the accumulation of AlCl 3 in different regions of the brain especially the hippocampus which is the domain for memory and learning [35,36].…”

Alzheimer's Disease: Pathophysiology, Hypotheses and Treatment Strategies

“…Adenosine receptors, especially adenosine A2A play pivotal role in modulation of neuronal function, linking the system to AD related cognitive deficits [19,20]. Caffeine which is a natural methylxanthine with a non-selective adenosine A1 and A2A receptor antagonist is well known as a neuromodulator that has associative effect on cognitive function and information processing as well as on motor behaviors [21].…”

“…It can also provide marked symptomatic and disease modifying benefits. For example, co-treatment with moderate doses of caffeine and nicotine has more pronounced protecting effect than each drug alone during induction of AD in rats [21]. Moreover, combination treatment using either EGCG & CoQ10 or EGCG & Vitamin E and Selenium has more pronounced effect than each one alone in minimizing the hazards of aluminum-induced AD in an experimental rat model of AD [22].…”

“…Moreover, combination treatment using either EGCG & CoQ10 or EGCG & Vitamin E and Selenium has more pronounced effect than each one alone in minimizing the hazards of aluminum-induced AD in an experimental rat model of AD [22]. In other word, reducing oxidative stress together with inflammatory mediators as well as both Aβ and tau pathologies attenuate both biochemical and histopathological alterations as well as cognitive deterioration associated the incidence and the progression of AD [21][22][23]. However, more researches and clinical trials are needed to evaluate and improve the quality of evidence associated with these multi-target directed strategies in the reduction of AD prevalence and incidence.…”