Effect of Curcumin, Exelon and their Combination on Brain in Alzheimer’s Disease-Induced Rats

Because of the continues rising in the number of patients who have Alzheimer’s disease (AD) throughout the twenty-first century, the looking for remedies increase by scientists. The treatment of AD remains a challenge due to an incomplete understanding of' reasons that lead to the selective neurodegeneration typical of Alzheimer’s brains. Among treatment for AD, the renewed interest in curcumin is rise for its potential medication. As kind of natural product curcumin with anti-AD properties is very important for prevention and treatment. The aim of the present study was evaluated the activity of curcumin in the recession of AD induced in adult male albino rats. The results showed that treatment of AD groups with curcumin or rivastigmine experienced significant decreased in brain AChE, Aβ (1-42), and MAD levels with respect to untreated group associated with significant increase in brain GSH, SOD, and CAT. activity. Further showed combination of curcumin with rivastigmine was more efficacious in treatment of AD as compared to their effect alone.

Kinetic characterization of rat brain acetylcholinesterase modulated by lead and cartap: the ameliorative effect of Citrus limon fruit juice

ObjectivesHuman exposure to heavy metals and pesticides is a worldwide major health problem. These environmental pollutants have been considered as the most neurotoxic agents and responsible to causing neurological toxicity. Plant-based therapeutic supplement may be used in the event of toxicity. Citrus limon contains several useful bioactive ingredients including flavonoids, dietary fiber, carotenoids, vitamins, pectin, minerals, and essential oils, which are responsible for its therapeutic potential. In the present investigation, we have studied the toxicity of heavy metals such as lead (Pb) and a carbamate pesticide such as cartap (Cp) on rat brain acetylcholinesterase (AChE).MethodsThe chemical characterization of C. limon involved determination of total antioxidants and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging activity using known methods. The AChE activity and its kinetic characterization were performed by assaying the enzyme activity at varying substrate concentrations, pH, temperature, and time of reaction. Its different kinetic parameters such as Ki, Vmax, Km, Kcat, and Kcat/Km were determined by using standard procedures. The amelioration potential of the extract was evaluated on the neurotransmission system of rat brain AChE treated with Pb, Cp, and their combination (Pb–Cp), considering their 50% inhibitory concentration (IC50) values.ResultsThe optimal activity of rat brain AChE was recorded at 25 µg of protein, pH of 7.4, substrate concentration [S] of 0.5 mM, and temperature of 37.4–40°C. The enzyme was stable for 10 min when incubated at 37.4 °C in vitro. The enzyme displayed 70% of its activity remaining even after 160 min of incubation in this condition. It may be stable up to 1 month when stored at −20°C. The IC50 values for Pb, Cp, and Pb–Cp were found to be 75, 2.9, and 5 mM, respectively. Pb, Cp, and Pb–Cp inhibited the activity of rat brain AChE in the noncompetitive, mixed, and uncompetitive manners, respectively, with their respective Ki values to be 675, 2.37, and 22.72 mM.ConclusionsThe results indicated that the Pb and Cp were able to cause significant alterations in the level and properties of AChE. However, the introduction of lemon juice on Pb- and Cp-treated AChE indicated protection of its activity from their adverse effects. The results may be useful in prospective therapeutic applications of lemon juice or as a food supplement to protect mammalian systems from adverse effects of these toxicants.

Long-term Administration of Lovastatin and Rivastigmine: An In Vivo Evaluation on Cognitive Functions and Brain Acetylcholinesterase Activity

Background. There is not much evidence illustrating that statins could be responsible for memory loss or dementia, although increased exposure to statins has been reported to cause cognitive side effects. The present study investigated the effect of lovastatin in combination with rivastigmine on cognitive function as well as brain acetylcholinesterase (AChE) activity in normal mice. Methods. The mice were categorized into four groups, and they were treated with normal saline, lovastatin, rivastigmine, and the combination of lovastatin and rivastigmine, respectively, by oral administration for 60 days. The treatment effect on cognitive functions was assessed by behavioral tests, namely, the passive avoidance test and spontaneous alternation test, as well as the measurement of brain AChE activity by Ellman’s method. Results. In this study, a significant reduction (P < 0.01) of brain AChE activity and positive effects (P < 0.01) on cognitive functions was observed in mice treated with the combination of lovastatin and rivastigmine as compared to rivastigmine alone. However, no significant differences (P < 0.05) were observed on brain AChE activity as well as cognitive functions in mice treated with lovastatin when compared with those treated with normal saline. Conclusion. This study suggested that lovastatin did not contribute to any improvements in cognitive functions and brain AChE activity, but it potentiated the effect of rivastigmine.

Original Article. Protection studies of new bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives (HNK-series) oximes against acute poisoning by dichlorvos (DDVP) in Swiss albino mice

The available antidotal therapy against acute poisoning by organophosphates involves the use of atropine alone or in combination with one of the oximes, e.g. 2-PAM, Obidoxime, TMB-4 or HI-6. Each of these oximes has some limitation, raising the question of the universal antidotal efficacy against poisoning by all OPs/nerve agents. In the present study, newly synthesized bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives (HNK-series) oximes were evaluated for their antidotal efficacy against DDVP intoxicated Swiss mice, in terms of the Protection Index (PI) and AChE reactivation in brain and serum. The inhibition concentration (IC50) was determined in brain and serum after optimizing the time point for maximum inhibition (60 min post DDVP exposure). AChE reactivation efficacy of the HNK series was evaluated at IC50 and compared with 2-PAM. HNK-102 showed a ~2 times better Protection Index (PI) as compared to 2-PAM against DDVP toxicity. IC50 at 60 min DDVP post exposure was found to be approximately one fifth and one half of the LD50 dose for brain and serum AChE, respectively. Out of three HNK oximes, HNK-102 & 106 at 0.20 LD50 dose significantly reactivated DDVP intoxicated brain AChE (p<0.05) as compared to 2-PAM at double IC50 dose of DDVP. In light of double PI and higher AChE reactivation, HNK 102 was found to be a better oxime than 2-PAM in the treatment of acute poisoning by DDVP.

Carbofuran Modulating Functions of Acetylcholinesterase from Rat Brain In Vitro

Carbofuran, a potential environmental xenobiotic, has the ability to cross blood brain barrier and to adversely influence brain functions. In the present study, the impact of carbofuran on the biophysical and biochemical properties of rat brain AChE has been evaluated in vitro. This enzyme was membrane-bound which could be solubilised using Triton-X100 (0.2%, v/v), a nonionic detergent, in the extraction buffer (50 mM phosphate, pH 7.4). The enzyme was highly stable up to one month when stored at -20°C and exhibited optimum activity at pH 7.4 and 37°C. AChE displayed a direct relationship between activity and varying substrate concentrations (acetylthiocholine iodide (ATI)) by following Michaelis-Menten curve. The Km and Vmax values as computed from the Lineweaver-Burk double reciprocal plot of the data were found to be 0.07 mM and 0.066 µmole/mL/min, respectively. The enzyme exhibited IC50 value for carbofuran equal to 6.0 nM. The steady-state kinetic studies to determine mode of action of carbofuran on rat brain AChE displayed it to be noncompetitive in nature with Ki value equal to 5 nm. These experiments suggested that rat brain AChE was very sensitive to carbofuran and this enzyme might serve as a significant biomarker of carbofuran induced neurotoxicity.

Bioconcentration and Acute Intoxication of Brazilian Freshwater Fishes by the Methyl Parathion Organophosphate Pesticide

Three species of freshwater Brazilian fishes (pacu,Piaractus mesopotamicus; piavussu,Leporinus macrocephalus, and curimbatá,Prochilodus lineatus) were exposed to an acute dose of 5 ppm methyl parathion organophosphate pesticide. Three to five individuals per species were exposed, one at a time, to 40 liters tap water spiked with Folidol 600. Pesticide concentrations and cholinesterase (ChE) activities were evaluated in serum, liver, brain, heart, and muscle. The bioconcentration of methyl parathion was similar for all studied fishes. Brain tissue showed the highest pesticide concentration, reaching 80 ppm after exposure for 30 min to methyl parathion. Three to 5 hours of 5 ppm methyl parathion exposure provoked the death of allP. lineatusat 92% brain AChE inhibition, whereas fish from the other two species survived for up to 78 hours with less than 80% brain AChE inhibition. Our results indicate that acute toxic effects of methyl parathion to fish are correlated with brain AChE sensitivity to methyl paraoxon.