Protective Effect of Monoisoamyl-2, 3-Dimercaptosuccinic Acid against Manganese-induced Neurotoxicity in Rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Awanish Mishra ◽  
Anjali Dahia ◽  
Amit Jaiswal
Keyword(s):  
Locomotor Activity ◽  
Protective Effect ◽  
Motor Coordination ◽  
Forced Swim Test ◽  
Intraperitoneal Administration ◽  
Dimercaptosuccinic Acid ◽  
Motor Dysfunction ◽  
Spontaneous Locomotor Activity ◽  
Rotarod Test ◽  
Essential Heavy Metal

Background: Apart from being an essential heavy metal, Manganese (Mn) serves as an important component of the antioxidant enzyme system in humans. Overexposure to manganese leads to the development of manganism, which is characterized by motor dysfunction along with neurodegeneration. The management of manganism often utilizes chelation therapy. In this regard, Monoisoamyl-2, 3-Dimercaptosuccinic Acid (MiADMSA) has been reported as a novel arsenic chelator, due to the presence of vicinal sulfhydril group. MiADMSA has been reported to reduce the level in divalent ions (like copper) therefore, it may be hypothesized that MiADMSA would be helpful in Mn-induced neurotoxicity. Objective: This study is envisaged to explore the protective effect of MiADMSA on Mn-induced neurotoxicity. Method: Mn exposure was carried out by intraperitoneal administration of Mn (as manganese chloride, 10 mg/kg; i.p.). The animals were treated with MiADMSA (50 mg/kg; p.o.) either alone or in combination with Mn. The effect of different treatments on neurobehavioral functions was observed by assessing spontaneous locomotor activity, motor rotarod test, and depression-like behavior in the forced swim test. After behavioral evaluations, all the animals were sacrificed and the brain and liver were isolated for metal estimations. Results: Mn exposure leads to loss of motor coordination as observed in spontaneous locomotor activity and rotarod test. However, treatment with MiADMSA significantly improved motor impairments as compared to Mn exposed animals. Accumulation of Mn in the liver and brain has been recorded with Mn exposure; however, MiADMSA treatment significantly reduced the Mn content from the liver and brain. Conclusion: The outcome of the study suggests that treatment with MiADMSA reversed Mn-induced neurotoxicity by reducing Mn load. Therefore, the use of MiADMSA may be suggested in manganese toxicity, after careful investigation.

Safety pharmacology of sibutramine mesylate, an anti-obesity drug

2005 ◽  
Vol 24 (3) ◽  
pp. 109-119 ◽  
Author(s):  
Eun-Joo Kim ◽  
Eun-Kyung Park ◽  
Kwee-Hyun Suh
Keyword(s):  
Locomotor Activity ◽  
Motor Coordination ◽  
Smooth Muscles ◽  
Methanesulfonic Acid ◽  
Intestinal Transport ◽  
Sleep Time ◽  
Isolated Rat Heart ◽  
Spontaneous Locomotor Activity ◽  
General Behaviour ◽  
Organ Systems

Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague / respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbitalinduced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric / Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

Toxicological Effects of a Mixture Used in Weight Loss Products: p-Synephrine Associated With Ephedrine, Salicin, and Caffeine

2012 ◽  
Vol 31 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Gabriela C. Schmitt ◽  
Marcelo D. Arbo ◽  
Andréia L. Lorensi ◽  
Érica S. Maciel ◽  
Carolina L. Krahn ◽  
...  
Keyword(s):  
Weight Loss ◽  
Locomotor Activity ◽  
Body Temperature ◽  
Motor Coordination ◽  
Citrus Aurantium ◽  
Rotarod Test ◽  
Commercial Products ◽  
Male And Female ◽  
Toxicological Effects ◽  
Activity Test

p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has been used for weight loss in dietary supplements. There are commercial products containing this substance associated to caffeine, salicin, and ephedrine. The aim of this study was to evaluate the acute toxicity of this mixture in mice of both sexes. The significative results observed after acute oral administration to male and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine, salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor activity and ptosis in all treated groups for both sexes. Seizures were also observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400 mg/kg), and piloerection (all treated groups) were significantly observed only in females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was confirmed through the spontaneous locomotor activity test, in which the number of crossings considerably decreased ( P < .01) in all treated groups. The rotarod test showed a decrease in motor coordination at 400 mg/kg. Body temperature decreased significantly ( P < .01) in all treated groups compared to controls. The results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin, and caffeine association; this toxicity augments the attentiveness on commercial products containing this mixture, given the expressive number of adverse events related to its utilization.

scholarly journals Motor Dyscoordination and Alteration of Functional Correlation Between DGKγ and PKCγ in Senescence-Accelerated Mouse Prone 8 (SAMP8)

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryosuke Tsumagari ◽  
Kenta Maruo ◽  
Takaaki Nakao ◽  
Shuji Ueda ◽  
Minoru Yamanoue ◽  
...  
Keyword(s):  
Motor Coordination ◽  
Open Field Test ◽  
Motor Dysfunction ◽  
Rotarod Test ◽  
Functional Correlation ◽  
Maze Test ◽  
Age Related ◽  
Y Maze ◽  
Equivalent Motor ◽  
Senescence Accelerated Mouse

Senescence-accelerated mouse prone 8 (SAMP8) is an animal model of age-related central nervous system (CNS) disorders. Although SAMP8 shows deficits in learning, memory, and emotion, its motor coordination has not been clarified. We have recently reported that DGKγ-regulated PKCγ activity is important for cerebellar motor coordination. However, involvement of the functional correlation between the kinases in age-related motor dyscoordination still remains unknown. Therefore, we have investigated the motor coordination in SAMP8 and involvement of the functional correlation between DGKγ and PKCγ in the age-related motor dyscoordination. Although 6 weeks old SAMP8 showed equivalent motor coordination with control mice (SAMR1) in the rotarod test, 24 weeks old SAMP8 exhibited significantly less latency in the rotarod test and more frequent slips in the beam test compared to the age-matched SAMR1. Furthermore, 24 weeks old SAMP8 showed the higher locomotor activity in open field test and Y-maze test. Western blotting revealed that DGKγ expression decreased in the cerebellum of 24 weeks old SAMP8, while PKCγ was upregulated. These results suggest that SAMP8 is a useful model of age-related motor dysfunction and that the DGKγ-regulated PKCγ activity is involved in the age-related motor dyscoordination.

scholarly journals The spontaneous motor activity of aqueous extract of Withania coagulans fruits in Swiss albino mice by actophotometer

2020 ◽  
Vol 9 (9) ◽  
pp. 1440
Author(s):  
Devesh D. Gosavi ◽  
Amit S. Kamdi ◽  
Suvarna M. Kalambe ◽  
Pankaj N. Bohra
Keyword(s):  
Locomotor Activity ◽  
Aqueous Extract ◽  
Motor Coordination ◽  
Spontaneous Locomotor Activity ◽  
P Value ◽  
Swiss Albino Mice ◽  
Cns Depressant ◽  
Withania Coagulans ◽  
Albino Mice ◽  
Cns Depressant Activity

Background: People spend about one third of their time in sleep every day. The various sedative and hypnotic medications used today have numerous side effects. In the late seventies a very little work was done on the Withania coagulans - a vulnerable species that is found scattered in the world. Therefore, it was essential to discover the CNS depressant activities of aqueous extract of Withania coagulans fruits in swiss albino mice by using actophotometer.Methods: The spontaneous locomotor activity was evaluated by using the actophotometer. The CNS depressant drugs decrease the locomotor activity in mice as they impair the motor coordination so that mice stay at one place for the longer time. Therefore, there is less disruption of the beams of light. This spontaneous locomotor activity time is statistically correlated among the control, standard and the test drugs.Results: There was statistically highly significant (p value <0.001) association observed between aqueous extract of Withania coagulans fruits with spontaneous locomotor activity in swiss albino mice on the actophotometer.Conclusions: The aqueous extract of Withania coagulans fruits demonstrated the CNS depressant activity in swiss albino mice by actophotometer.

scholarly journals The effects of resveratrol on rat behaviour in the forced swim test

2013 ◽  
Vol 141 (9-10) ◽  
pp. 582-585 ◽  
Author(s):  
Janko Samardzic ◽  
Dragana Jadzic ◽  
Milan Radovanovic ◽  
Jasna Jancic ◽  
Dragan Obradovic ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Digital Camera ◽  
Spontaneous Locomotor Activity ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Significant Difference ◽  
Post Hoc ◽  
One Way Anova

Introduction. The trans-isomer of resveratrol is the active ingredient of Poligonum cuspidatum, known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders. It is also found abundantly in the skin of red grapes and red wine. Previous studies have suggested that trans-resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, as well as neuroprotective properties and procognitive effects. Objective. The goal of the present study was to examine the influence of trans-resveratrol on behavior in rats and its antidepressant properties. Methods. Male Wistar rats were treated intraperitoneally (i.p.) with the increasing doses of trans-resveratrol (5, 10 and 20 mg/kg) or vehicle (dimethyl sulfoxide - DMSO), 30 minutes before testing of the spontaneous locomotor activity or forced swimming. For the experiments, the behavior of the animals was recorded by a digital camera, and the data were analyzed by one-way ANOVA, followed by Tukey post-hoc test. Results. Testing of spontaneous locomotor activity, after the application of vehicle or increasing doses of trans-resveratrol, showed no statistically significant difference between groups (p>0.05). In the forced swim test, one-way ANOVA indicated statistically significant effects of trans-resveratrol (p<0.001). Tukey post-hoc test showed that resveratrol significantly decreased immobility time at the doses of 10 mg/kg and 20 mg/kg, manifesting the acute antidepressant-like effects. There were no statistically significant differences between the resveratrol treatment of 5 mg/kg and vehicle (p>0.05). Conclusion. The results from our study suggest that trans-resveratrol produces significant effects in the central nervous system. After single application, it has acute antidepressant effects, but without influence on locomotor activity.

Physical exercise protects dynamic balance and motor coordination of rats treated with vincristine

2020 ◽  
Vol 19 (5) ◽  
pp. 336
Author(s):  
Luiza Minato Sagrillo ◽  
Viviane Nogueira De Zorzi ◽  
Luiz Fernando Freire Royes ◽  
Michele Rechia Fighera ◽  
Beatriz Da Silva Rosa Bonadiman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Locomotor Activity ◽  
Physical Exercise ◽  
Motor Coordination ◽  
Dynamic Balance ◽  
Exercise Group ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Stress Damage ◽  
Training Protocol

Physical exercise has been shown to be an important modulator of the antioxidant system and neuroprotective in several diseases and treatments that affect the central nervous system. In this sense, the present study aimed to evaluate the effect of physical exercise in dynamic balance, motor coordination, exploratory locomotor activity and in the oxidative and immunological balance of rats treated with vincristine (VCR). For that, 40 adult rats were divided into two groups: exercise group (6 weeks of swimming, 1h/day, 5 days/week, with overload of 5% of body weight) and sedentary group. After training, rats were treated with 0.5 mg/kg of vincristine sulfate for two weeks or with the same dose of 0.9% NaCl. The behavioral tests were conducted 1 and 7 days after each dose of VCR. On day 15 we carried out the biochemical analyzes of the cerebellum. The physical exercise was able to protect against the loss of dynamic balance and motor coordination and, had effect per se in the exploratory locomotor activity, and neutralize oxidative stress, damage DNA and immune damage caused by VCR up to 15 days after the end of the training protocol. In conclusion, we observed that previous physical training protects of the damage motor induced by vincristine.Key-words: exercise, oxidative stress, neuroprotection, cerebellum.

Profile of a short-acting κ-antagonist, LY2795050, on self-grooming behaviors, forced swim test and locomotor activity: sex comparison in mice

2021 ◽  
pp. 026988112199688
Author(s):  
Eduardo R Butelman ◽  
Caroline Baynard ◽  
Bryan D McElroy ◽  
Thomas E Prisinzano ◽  
Mary Jeanne Kreek
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Male And Female ◽  
Short Acting ◽  
Swim Test ◽  
Central Nervous System Dysfunction ◽  
Forced Swim ◽  
Males And Females ◽  
The Impact ◽  
Κ Receptor

Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists.

scholarly journals Evaluation of Additive or Synergistic Effect of Piper nigram and Ocimum sanctum Extracts for their Antidepressant Activity

2021 ◽  
Vol 70 (2) ◽  
Author(s):  
K. Mohana Rao ◽  
Siva B. ◽  
Mahendra U. ◽  
Vinay K. ◽  
A. Narendra Babu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Ocimum Sanctum ◽  
Alcoholic Extract ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Wide Range

Depression is a state of excessive sensitivity to criticism, fear of rejections, lack of self-interest, loss of pleasure. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. In recent times, research on the plants increased globally and so many plants provide the evidence to cure diseases. Ocimum sanctum, popularly known as Tulsi is one of the sacred herbs for Hindus in the Indian subcontinent. It has a versatile role in traditional medicine. The fruits of Piper nigrum are used to make black pepper. This hotly pungent spice is one of the earliest known and most widely used spices in the world today. Wide range of animal tests for antidepressant agents are commonly used. The Forced swim test and Tail suspension test in mice were mostly used. Hence in the present study Forced swim test was used as animal model of depression. In present study immobility time in Forced swim test was significantly decreased by a combination of Piper nigrum fruit extract and Ocimum sanctum extract treated groups compared to control group. The combination of extracts (50 mg/kg each) activity was comparable to standard drug Fluoxetine. Treatment with extracts does not modify the locomotor activity of mice, which indicates that they exert antidepressant effects without modifying significantly locomotor activity. Therefore, the present study confirms the combination of alcoholic extract of Piper nigrum (AEPN) fruit and aqueous extract of Ocimum sanctum (AEOS) possessing additive/synergistic antidepressant activity.

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