scholarly journals Effect of novel phenothiazine derivatives on brain dopamine in Wistar rats

Author(s):  
Chandravadivelu Gopi ◽  
Vedula Girija Sastry ◽  
Magharla Dasaratha Dhanaraju

Abstract Background Neurotransmitters are involved in several functions in the brain and the body of living things. Changes in the level of neurotransmitters in the brain are associated with several illnesses. Some of the drugs are controlling the neurotransmitter by adjusting the level in the brain and are exclusively used in the treatment of psychological disorders. The purpose of the study was to find out the effect of novel synthesised phenothiazine derivatives (GC1, GC2 and GC8) either alone (7.5 mg/kg or 15 mg/kg, oral) or in combination with amphetamine on the experimental animals. Results Dopamine level in rat brain was estimated by a spectroscopic method using the UV-visible double beam spectrophotometer at 735 nm. The results revealed that these derivatives blocked the brain dopamine level significantly. The compound GC8 (15 mg/kg) significantly reduced the level of dopamine (0.151 ± 0.04, 0.284 ± 0.03) as similar to that of a standard drug. Furthermore, compounds GC2 (15 mg/kg) and GC1 (15 mg/kg) exhibited a varying level of dopamine inhibition level and have been found at 0.203 ± 0.06 μg/ml, 0.302 ± 0.04 μg/ml, 0.234 ± 0.02 μg/ml and 0.318 ± 0.07 μg/ml, respectively, after the administration of these derivatives either alone or in combination with amphetamine. Conclusions The study revealed that the compound 2-amino-6-(3-hydroxy-4-methyl phenyl) pyrimidine-4-yl) (7-chloro-10-(3- (N, N-dimethylamino) propyl)-10H-phenothiazine-3-yl) methanone (GC8, 15 mg/kg) extensively reduced the dopamine level. The order of dopamine-inhibiting effect of the selected compound was found to be GC8 > GC2 > GC1. The increased body weight and relative brain-body weight were also observed in the tested animals due to more intake of food and fluid retention. Graphical abstract

Author(s):  
Javid Mansuri ◽  
Archana Paranjape

Objective: Evaluation of the anti-obesity effect of aqueous extract of Mucuna pruriens seeds on rats.Methods: Male Sprague-Dawley (SD) rats were subjected to high-fat diet (HFD) for 12 wk. L-DOPA (12.5 mg/kg, p. o.) as standard drug and aqueous extract of Mucuna pruriens (AEMP) seeds (200 mg/kg, p. o. and 400 mg/kg, p. o.) as test drugs were administered in last 4 wk along with HFD. Body weight, food intake, body mass index (BMI), serum total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) levels were measured at the end of fourth, eighth and twelfth wk, while white adipose tissue (WAT) mass and brain dopamine levels were measured at the end of the twelfth wk.Results: AEMP (200 mg/kg, p. o.) and (400 mg/kg, p. o.) treated groups showed a significant decrease in food intake and weight gain without altering BMI. Moreover, TG levels were lower in treated groups as compared to the HFD group, but no significant changes were observed in TC and HDL levels. L-DOPA-treated group showed a significant decrease in body weight, food intake, BMI and WAT. Both AEMP and L-DOPA-treated groups showed an increase in brain dopamine levels as compared to disease control group (p<0.05).Conclusion: L-DOPA and AEMP showed anti-obesity activity by reducing body weight gains, food intake and WAT weights; modulating TG with increased brain dopamine level which correlates to the inhibitory action of dopamine on reward mechanism. 


Author(s):  
Pooja Pooja ◽  
Mazumder Avijit ◽  
Soumya Das

Diabetes is a chronic disease which characterized by hyperglycemia (elevated or abnormally high blood sugar levels) and other metabolic disturbances, including metabolism of lipids and haemostasis. Caesalpinia pulcherrima has previously showed strong anti-diabetic and hepatoprotective potential. The present research work was to investigate the anti-diabetic activity and hepatoprotective activity Caesalpinia pulcherrima in streptozotocin-induced (STZ) diabetic rats. The dose-dependent effects of 45days oral treatment with methanol extract of plant (200 and 300mg/kg) of CPAE on body weight, blood glucose level, total protein, albumin, liver marker enzymes and carbohydrate metabolizing enzymes were evaluated in STZ-induced diabetic rats. Oral administration methanolic extract of Caesalpinia pulcherrima of showed significant restoration of the body weight and decrease in the blood glucose level, liver marker enzymes (ALT, AST ALP) and carbohydrate metabolizing enzymes were observed in diabetic rats. These results suggest that fruit extract of Caesalpinia pulcherrima has valuable anti-diabetic activity in STZ-induced diabetic rats which is comparable to the standard drug metformin and hence might be of use in the management of diabetes.


1908 ◽  
Vol 8 (5) ◽  
pp. 565-600 ◽  
Author(s):  
H. W. Armit

Nickel carbonyl poisoning is a particular instance of nickel poisoning.The lethal dose of nickel varies according to the method of application. When applied by subcutaneous injection, the physical condition of the compound influences the rate of absorption and therefore relatively large quantities may be required. In rabbits, the lethal dose is about 7½ mgrs. per kilogram body weight under the most favourable conditions when applied subcutaneously. In cats it is about 12½ mgrs. per kilogram body weight. When applied intraperitoneally, the absorbing surface is considerably larger and consequently the dose required to kill is smaller. In rabbits it is less than 7 mgrs. When applied in the form of nickel carbonyl vapour one meets with the most favourable conditions for rapid absorption and the dose is therefore still smaller. Rabbits die after the absorption of between 3 and 4 mgrs., while cats die after absorbing about 8½ mgrs. per kilogram body weight.In the lungs, nickel carbonyl is dissociated and a nickel compound, probably the hydrated sub-carbonate, is deposited on the respiratory surface.The nickel is dissolved from the respiratory surface by the tissue fluids and is then taken up by the blood.Some of the nickel finds its way directly through the lymphatic channels into the bronchial glands.In the dissolved condition, the nickel enters into complex combination with some constituent of the body.The nickel is carried by the blood to the tissues, but a selective absorption is exercised by the brain and adrenals. In the case of other forms of nickel poisoning, the lungs also exert this specific selection. The nickel only stays for a short time in these organs.The specific pathological changes which are produced by nickel in these organs are primarily a degeneration of the endothelial cells of the capillary vessels. It is possible that some further primary action is exercised on the ganglion cells in the brain and on the parenchyma cells of the adrenals.The haemorrhages follow as the result of the fatty degeneration of the vessel walls and secondary changes result from the effects of the haemorrhages.The nickel is excreted by the kidneys and intestines.The method of poisoning with iron carbonyl is similar to that of nickel poisoning, but the amount necessary to kill in the former case is larger.Iron carbonyl poisoning like nickel carbonyl poisoning is merely a specific instance of metallic poisoning.Iron acts in a similar manner to nickel on the walls of capillary vessels, but no evidence of selection by any special tissues was obtained.Cobalt has a toxicological action which is identical to that of nickel. The lethal dose however is higher than that of nickel and lower than that of iron.After the inhalation of a quantity of nickel or iron carbonyl which is greater than the minimum required to kill, no form of treatment was found to avert death.It is with much pleasure that I again express my gratitude to Dr Ludwig Mond, F.R.S., for having rendered this investigation possible, by defraying all the expenses, and by giving me the benefit of his advice.I further desire cordially to thank Dr C. J. Martin, F.R.S., and the other members of the Staff of the Lister Institute, who have at all times been ready and willing to assist me. The work has necessitated incursions into several branches of science, and has required the acquisition of a variety of methods. I have made free use of their kind collegiality and am glad to avail myself of this opportunity of recording my indebtedness.The literature of the subject has been given in Part I, q.v.


1972 ◽  
Vol 27 (3) ◽  
pp. 527-536 ◽  
Author(s):  
J. W. T. Dickerson ◽  
P. C. R. Hughes ◽  
P. A. McAnulty

1. Weanling (24-d-old) rats of a black and white hooded strain were allowed free access for 28 d to a diet containing 5% casein supplemented with methionine, and sucrose as the carbohydrate. Controls were fed on a 25% casein diet with a corresponding reduction in sucrose. Animals given the deficient diet were killed either at 52 d of age or after subsequent rehabilitation on the 25% casein diet when aged 140 d. These animals were compared with controls killed at these two ages and at the start of the experiment.2. The skeletons were X-rayed, skeletal maturity was determined according to a scoring system, and various bones were measured. The forebrain and cerebellum were analysed for cholesterol and DNA and the brain stem for cholesterol only. The DNA content of the paired quadriceps muscles and the livers was also determined.3. On the low-protein diet the body-weight rose by 7 g compared with the control value of 115 g. On rehabilitation, the body-weight of the previously malnourished group showed the expected growth spurt, but failed to attain that of the controls at 140 d.4. With the exception of the pelvis width, all the bones grew a little during the period on the low-protein diet. After rehabilitation, the hind limb, pelvis, iliac and spine lengths and the bi-iliac width remained smaller than these measurements in the corresponding controls, whereas there was no difference in the length of the fore limb, width of the pelvis or in the bone maturity score.5. The forebrains and cerebellums of the malnourished rats did not increase in weight, whereas some increase occurred in the brain stem. The concentration of cholesterol in the forebrains of the deficient animals was the same as that in controls of the same age, but on rehabilitation the concentration did not rise to the control value. The concentration of cholesterol in the cerebellum and brain stem of the deficient rats was lower than in controls of the same age but, whereas that in the cerebellum attained an almost normal level on rehabilitation, that in the brain stem remained significantly lower. The low-protein diet prevented the normal increase in cerebellum DNA and the amount remained low in the rehabilitated animals.6. The experimental diet caused a complete cessation of growth of the quadriceps muscles, and even after rehabilitation they weighed less than their controls. The DNA content, however, was not significantly lower.7. The low-protein diet did not permanently affect either the weight or DNA content of the liver.


2020 ◽  
Vol 2 (2) ◽  
pp. 113-116
Author(s):  
Indah Permata Sari ◽  
Muhammad Ichwan ◽  
Yahwardiah Siregar

D-galactose is aldohexose which occurs naturally in the body, including in the brain which is found in lactose disaccharides in honey, beets and milk products. Needed in the body for lactose formation during the process of lactogenesis. Provision of large amounts of D-galactose can cause oxidative damage to various tissues and organs. The purpose was to see changes in body weight in male rats after being given a D-galactose injection. Samples using male mice aged 8 weeks with a weight of ± 30 grams, the number of samples was 6 mice swiss webster strain. intra-peritoneal injection of D-galactose is given for 6 weeks every day (150 mg / kg / bb). The results of this study indicate that the statistical analysis is significant p <0.05 (p = 0.016). The conclusion after being given injection of D-galactose for 6 weeks every day intra peritoneally was found D-galactose had an effect on the weight gain of male mice.


2020 ◽  
Vol 10 (3-s) ◽  
pp. 37-42
Author(s):  
Hadjer Bekhedda ◽  
Norredine Menadi ◽  
Abbassia Demmouche ◽  
Abdelaziz Ghani ◽  
Hicham Mai

Introduction: Aluminum (Al) has the potential to be neurotoxic in human and animals, is present everywhere in the environment, many manufactured foods and medicines and is also added to drinking water for purification purposes and tooth paste cosmetic products They accumulate in living organisms and disrupt balances, and accumulate in the body biological systems, causing toxic effects (They may affect the nervous system, kidney, liver, respiratory or other functions). Nervous system is a vulnerable target for toxicants due to critical voltages which must be maintained in the cells and the all responses when voltages reach threshold levels. Objective This study aimed to expose the impact of aluminum chloride (AlCl3) on brain architecture. Methods: In our study, twenty healthy female rats were intraperitoneal administered of aluminum chloride (ALCL3) at 10 mg / kg body weight with consecutively for 15 day Result. The results showed a highly significant reduction in body weight (p<0.0001).  This is because aluminum has an anorectic effect contrariwise, there is no significant impact of aluminium exposure has been observed with respect to brain weight and relative brain weight respectively (p<0.912), (p<0.45). The histological study describes the alterations in the brain marked tissue necrosis and cytoplasmic vacuolations and karyopyknosis of neuronal cells of the brain. Conclusion; Aluminum is a toxic heavy metal and a ubiquitous environmental pollutant. It can alter the permeability of the blood-brain barrier and enter the brain, severely affecting the functioning of the nervous system. Keywords: Toxicity, brain, Aluminium chloride, Rats female, necrosis.


2018 ◽  
Vol 7 (2) ◽  
pp. 193-210
Author(s):  
Maria Victória Branco Flores ◽  
Tuany Eichwald ◽  
Analú Mantovani ◽  
Viviane Glaser ◽  
Carine Raquel Richter Schimitz ◽  
...  

O Manganês (Mn) é um metal essencial para o organismo. É distribuído no ambiente e utilizado em processos industriais. Apesar de essencial, é neurotóxico à exposições cumulativas, causando uma desordem neurológica, o Manganismo. O estudo avaliou o efeito da administração subaguda de Mn sob a forma de cloreto e acetato de Mn, sobre a função mitocondrial e parâmetros oxidativos no encéfalo, bem como o acúmulo deste metal no encéfalo e tecidos periféricos de ratos adultos. Os ratos receberam 6 mg/kg de Mn i.p. na forma de cloreto ou acetato de Mn, 5 dias/semana por 4 semanas. O grupo controle recebeu solução salina 0,9% pela mesma via de administração e mesmo período. Foi mensurada a concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS) e grupamentos NPSH, a atividade dos complexos I e II da cadeia respiratória no encéfalo e/ou estruturas cerebrais, bem como o peso corporal e a concentração de Mn e Fe no soro, encéfalo, tecido renal e hepático. Foi observada uma diminuição no ganho de peso corporal dos animais que receberam o Mn, um aumento na concentração/depósito de Mn no soro, encéfalo e tecido renal, tanto na forma de cloreto e acetato de Mn, quando comparados com o grupo controle. Além disso, houve um aumento significativo no conteúdo de NPSH no encéfalo e, embora não significativo, uma tendência de aumento da concentração de TBARS, no grupo que recebeu cloreto de Mn. Ainda, foi verificada uma inibição na atividade do complexo I no estriado dos animais expostos ao cloreto de Mn. Não houve diferença entre os grupos nas atividades do complexo I e II no encéfalo e hipocampo. Em conjunto, os dados indicam que a exposição ao Mn em baixas doses contribui para o desenvolvimento de estresse oxidativo e disfunção mitocondrial no SNC, com aparente predileção de dano ao estriado.Palavras-chave: Manganês. Exposição subaguda. Parâmetros oxidativos. Função mitocondrial. MANGANESE SUBACUTE INTOXICATION IN ADULT WISTAR RATS: EVALUATION OF OXIDATIVE PARAMETERS IN CNS AND METAL DEPOSITION IN DIFFERENT TISSUES ABSTRACT: Mn is an essential metal to the organism. It is distributed in the environment and used in industrial processes. Although essential, it is neurotoxic to cumulative exposures, and can cause a neurological disorder, called Manganism. This study evaluated the effect of subacute Mn as chloride and acetate of Mn administration on mitochondrial function and oxidative parameters in adult rat brain, as well as the accumulation of this metal in the brain and peripheral tissues. The rats received 6 mg/kg of Mn i.p., as Mn chloride or Mn acetate, 5 days/week for 4 weeks. The control group received 0.9% of saline solution in the same way of administration and in the same period. It was measured the concentration of thiobarbituric acid reactive substances (TBARS) and NPSH groups, the activity of mitochondrial complex I and II in brain and/or in the brain structures, as well as the body weight and the concentration of Mn and Fe accumulation. It was observed a decrease on body weight gain in animals exposed to Mn and an increase of concentration/deposit of Mn in serum, brain and kidney, in the both Mn chloride and acetate form when compared to the control group. In addition, there was a significant increase in brain NPSH content and, although it was not significant, a trend of increasing on TBARS concentration in the group that received Mn. Besides that, a significant inhibition of complex I activity was observed in the striatum of the animals exposed to Mn. There was not difference between groups on complex I and II in the brain and hippocampus. Together, these data indicate that exposure to Mn at low doses contributes to the development of oxidative stress and mitochondrial dysfunction in the CNS, with apparent predilection of striatum damage.Keywords: Manganese. Subacute exposure. Oxidative parameters. Mitochondrial function.


Author(s):  
I. A. Hassan ◽  
I. Abdulraheem ◽  
H. O. Emun ◽  
D. M. Lawal

Aims: This study was aimed at investigating the antihyperglycemic effect of a combined extract of Vernonia amygdalina and croton zabensicus compare with a hypoglycemic drug, glibenclamide. Methodology: Twenty 20 experimental animals were used (albino rats); the rats were divided equally into four groups of five rats each; namely A (control), B (glibenclamide 10 mg/kg body weight), C (synergetic treatment 1000 mg/kg body weight), D (synergetic treatment 500 mg/kg of body weight). Diabetes was induced intraperitoneal using Alloxan Monohydrate to all the animals and their blood glucose rise above 200 mg/dl. Results: It was observed that group B and group C treated with glibenclamide (10 mg/kg body weight) and synergetic aqueous extract (1000 mg/kg body weight) show significant decrease in the blood glucose level from 451.75 mg/dl to 64.50 mg/dl and 339.50 mg/dl to 182.50 mg/dl respectively compared with group D with 278.25 mg/dl to 194.75 mg/dl. However, a change was also observed in the body weight of the groups; Group A (Normal control) showed a continuous increase in the body weight, Group B, C and D were observed to have decreased in body weight from induction period, but a steady increase was observed as treatment commences. Conclusion: Hence this combined extract can be used as antihyperglycemic; only that it is slower in remediation compared with the glibenclamide; but without side effect, as may be in the case of most standard drug.


Author(s):  
Jashia Mozib Porshi

Fighting against anxiety caused by COVID 19 pandemic is inevitable to mental health programs in every country amid this pandemic circumstance. A 2019 study found that music encourages the release of dopamine in the synapses of the brain. Dopamine is a neurotransmitter that plays an important role in our cognitive, emotional and behavioral functioning known as the “happy hormone”. It helps create the feeling of pleasure. Whilewe have long known that music improves mood, there’s increasing evidence that it can also contribute to mental & physical health. Being COVID 19 front line warriors, Doctors and police personnel go through exhausting work schedules stretching up to 12 hours or more a day and many of them are finding music therapy a tool to ease their stress levels. When the body is stressed, it may feel tense & tight that may require music therapy helping to facilitate relaxation to reduce anxiety.


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