Herbal snuff (AK-47 and HAM) induce oxidative stress and increase acetylcholinesterase enzyme activity in rat brain

Snuff has resurfaced not only in western countries but in Africa including Nigeria. It is now almost generally acceptable, among young and old in Nigeria. This research was designed to investigate the Effect of Hajiya Aisha Manpower (HAM) and AK-47 on Antioxidant Status and Acetylcholinesterase enzyme activity (AchE) of Wister Albino Rats. Thirty (30) Wister rats (110-120 g) were arbitrarily divided into five groups. Group1 (control); received only distilled water. Groups 2 and 3 (received 6 mg and 3 mg/kg b.w.t of HAM respectively). Groups 4 and 5 (received 6 mg and 3 mg/kg b.w.t AK-47 of respectively). After two months of treatments, the rats were anesthetized, blood samples were taken through heart puncture and brains of all rats were isolated and homogenized. The Result revealed Non-significant decrease in Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and concomitant increase in GSH levels in treatment groups were observed in relation to the control. While a substantial increase (p˂ 0.5) in MDA was detected in treatment groups. Brain AchE activity increased significantly in all treatment groups in relation to the control. We conclude that Both AK-47 and HAM at high concentration induce oxidative stress, decreased antioxidant enzyme activities and promote degradation of acetylcholine in rat brain homogenate.

Design, synthesis and evaluation of benzimidazole-NsCOXis hybrids for the treatment of Alzheimer’s disease

Usage of an acetylcholinesterase (AChE) inhibitor and a non-selective COX inhibitor (NsCOXi) have been documented to exhibit significantly protective and recuperative effects in AD patients. Therefore, it is hypothesised that a compound capable of exhibiting both AChE inhibition and anti-inflammatory activities can be potential pluripotent drug candidate for de-accelerating the progression of AD, as well as for providing relief from the associated inflammatory pathological indications. The present study involves the coupling of ibuprofen (IB) or naproxen (NP) to varied disubstituted amines (AChE inhibitor pharmacophore) through benzimidazole to develop two series of compounds i.e. IB01-IB05 and NP01-NP05 as pluripotent anti-AD compounds. All target compounds are evaluated for in vitro AChE inhibitory and COX inhibitory activities. Compounds IB01-IB05 are found more potent as compared to NP01-NP05. Compound IB04 being the most active in in vitro evaluation is selected for in vivo evaluation of memory restoration using scopolamine-induced amnesia model in mice. It significantly reverses the scopolamine-induced changes (i.e., escape latency time, mean time spent in target quadrant, brain AChE activity and oxidative stress) in a dose-dependent manner. IB04 at higher dose i.e. 8 mg/kg is significantly effective in lowering AD manifestation in comparison to donepezil. The findings indicate that Benzimidazole-NsCOXi derivatives having pyrrolidine moiety may prove a useful template for the development of new chemical moieties against AD with multiple potencies.

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.

Rosmarinus officinalis Essential Oil Improves Scopolamine-Induced Neurobehavioral Changes via Restoration of Cholinergic Function and Brain Antioxidant Status in Zebrafish (Danio rerio)

Rosmarinus officinalis L. is a traditional herb with various therapeutic applications such as antibacterial, antioxidant, anti-inflammatory, antidepressant, and anticholinesterase activities, and can be used for the prevention or treatment of dementia. In the present study, we tested whether Rosmarinus officinalis L. could counteract scopolamine-induced anxiety, dementia, and brain oxidative stress in the zebrafish model and tried to find the underlying mechanism. Rosmarinus officinalis L. essential oil (REO: 25, 150, and 300 µL/L) was administered by immersion to zebrafish (Danio rerio) once daily for eight days while scopolamine (100 µM) treatment was delivered 30 min before behavioral tests. The antidepressant and cognitive-enhancing actions of the essential oil in the scopolamine zebrafish model was measured in the novel tank diving test (NTT) and Y-maze test. The chemical composition was identified by Gas chromatograph–Mass spectrometry (GC-MS) analysis. The brain oxidative status and acetylcholinesterase (AChE) activity was also determined. REO reversed scopolamine-induced anxiety, memory impairment, and brain oxidative stress. In addition, a reduced brain AChE activity following the administration of REO in scopolamine-treated fish was observed. In conclusion, REO exerted antidepressant-like effect and cognitive-enhancing action and was able to abolish AChE alteration and brain oxidative stress induced by scopolamine.

Interactive Effects of Sertraline and Diphenhydramine on Biochemical and Behavioral Responses in Crucian Carp (Carassius auratus)

The ecotoxicity of psychiatric pharmaceuticals to aquatic organisms is being increasingly recognized. However, current ecological studies focus on the effects of individual psychiatric pharmaceuticals, with little attention being given to their combined effects. In this study, the interactive effects of two psychiatric pharmaceuticals, sertraline (SER) and diphenhydramine (DPH), on bioconcentration and biochemical and behavioral responses were investigated in crucian carp (Carassius auratus) after seven days of exposure. DPH was found to increase the accumulation of SER in fish tissues relative to SER-alone exposure. In addition, the mixture of SER and DPH significantly changed the activities of antioxidant enzymes and led to significant increases in malondialdehyde content, relative to SER alone. Concerning the neurotoxicity, relative to SER-alone exposure, brain AChE activity was significantly enhanced in fish following the combined exposure. Regarding behavioral responses, swimming activity and shoaling behavior were significantly altered in co-exposure treatments compared with the SER alone. Moreover, the inhibition effects on the feeding rates were increased in co-exposure treatments compared to SER alone. Collectively, our results suggest that the mixtures of psychiatric pharmaceuticals may pose more severe ecological risks to aquatic organisms compared to these compounds individually.

EFFECT OF ECLIPTA ALBA ON SCOPOLAMINE INDUCED AMNESIA IN MICE

The present study deals with the evaluation of potential effects of Eclipta alba (EA) in memory impairment of mice. Memory impairment was induced by scopolamine (3 mg/kg, i.p) in animals. To assess learning and memory in mice Morris water maze test was employed. The acetylcholinestrase enzyme (AChE) activity in brain was measured to evaluate the central cholinergic activity. The levels of thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH)in brain were estimated to assess the degree of oxidative stress. Scopolamine treatment produces significant impairment of learning and memory in mice, as reflected by a significant decrease in MWM performance. Scopolamine also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. EA (300 and 600 mg/kg,oral) significantly prevented scopolamine-induced learning and memory deficits along with decrease of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that Eclipta alba has significant protective action against scopolamine induced memory deficits in mice that can be attributed to its anti AChE and anti oxidant actions. Keywords: Alzheimer disease, Oxidative stress, Morris water Maze, Scopolamine

In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

Different Enzymatic Activities in Carp (Cyprinus Carpio L.) as Potential Biomarkers of Exposure to the Pesticide Methomyl

This study investigated the influence of the pesticide methomyl on different enzymatic activities in carp. The fish were exposed to a sub-lethal concentration (0.34 mg L-1) of methomyl for 15 days. On days 4 and 15, catalase (CAT) and glutathione-S-transferase (GST) activities were measured in the liver and gills. Acetylcholinesterase (AChE) activity in brain and muscle was also determined. Liver catalase activity slightly increased in exposed fish when compared to controls, but it was statistically significant only at the beginning of the experiment. No changes in CAT activity in the gills of exposed and control animals were observed (mean values were in the range 10.7-11.7 nmol min-1 per mg of protein). Liver GST activity was slightly inhibited in the exposed animals at the beginning of the study; however, it was significantly inhibited in the gills. Brain AChE activity was diminished throughout the experiment and significantly decreased after 96 h of exposure compared to controls (0.041 vs. 0.075 nmol min1 per mg of protein; p<0.001). Our findings suggest that CAT, GST, and AChE are reliable biomarkers of effect after exposure to methomyl.

Diazinon mediated biochemical changes in the African toad (Bufo regularis)

The sublethal toxicity of diazinon to the adult African toad, <em>Bufo regularis</em> was assessed using an integration of biomarkers. Changes in acetylcholinesterase (AChE), corticosterone and total protein levels were assessed in the serum, brain, liver, lungs and gastrointestinal tract (GIT) and the results supported by bioaccumulation data. The biomarkers were chosen as indicators of key physiological functions: AChE for neurotoxicity, corticosterone and total protein levels as indicators of oxidative stress. Toads were exposed to 0.01, 0.02, 0.03 and 0.04 g/L for 28 days. Brain AChE activity reduced by 96% in the highest concentration (0.04 g/L) compared to the control brain. Similarly, AChE activities in serum, liver, lungs and GIT tissues (88%, 88%, 87, 87% umg-1 protein respectively) were also inhibited in the toads. Corticosterone and total protein levels in the tissues decreased compared to the control. The accumulation results obtained showed accumulation in the tissues (liver&gt;serum&gt;brain&gt; lung&gt;GIT), with a direct relationship between tissue concentration and changes in the biochemical indices. The alterations in all the indices were significantly concentration dependent. The biomarkers described in this study could be useful complementary indices in the risk assessment of diazinon pesticide.