scholarly journals Comparative effects of meso-2,3-dimercaptosuccinic acid, monensin, and salinomycin on cadmium-induced brain dysfunction in cadmium-intoxicated mice

2017 ◽  
Vol 10 (3) ◽  
pp. 107-113 ◽  
Author(s):  
Juliana Ivanova ◽  
Emilia Petrova ◽  
Kalina Kamenova ◽  
Yordanka Gluhcheva

AbstractCadmium (Cd) is a risk factor for neurodegenerative diseases. The purpose of this study was to compare the effects ofmeso-2,3-dimercaptosuccinic acid (DMSA) and the polyether ionophorous antibiotics monensin and salinomycin on Cd-induced neurodegenerative alterations in mice. The results show that subacute intoxication of mice with Cd (II) acetate (20 mg/kg body weight (BW) for 14 days) caused a significant accumulation of cadmium (Cd) in the brain. Treatment of Cd-exposed mice with DMSA (20 mg/kg BW for 14 days) significantly increased the Cd concentration in the brains compared to those of the Cd-treated group. However, administration of monensin (20 mg/kg BW for 14 days) or salinomycin (20 mg/kg BW for 14 days) significantly reduced the Cd concentration in the brains of Cd-treated mice compared to the toxic control group. Histopathological analysis of brain tissues from the Cd-treated mice revealed that Cd induced neuronal necrosis, characterized by many shrunken, darkly stained pyknotic neurons with prominent perineuronal spaces. Whereas monensin and salinomycin significantly reduced the adverse effects of Cd on brain morphology of Cd-treated mice, DMSA did not. Monensin slightly increased the copper and iron endogenous levels in the brains of Cd-exposed mice compared to those of the untreated mice. Salinomycin did not affect the concentrations of biometal ions in the brain of Cd-exposed mice compared to untreated controls. The results demonstrated salinomycin to be a better potential chelating agent for treatment of Cd-induced brain injury compared to DMSA and monensin.

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.


2014 ◽  
Vol 7 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Juliana Ivanova ◽  
Yordanka Gluhcheva ◽  
Sonja Arpadjan ◽  
Mariana Mitewa

ABSTRACT Cadmium (Cd) is a well-known nephrotoxic agent. Cd-induced renal dysfunction has been considered as one of the causes leading to the development of hypertension. The correlation between Cd concentration in blood and urine and cardiovascular diseases has been discussed in many epidemiological studies. A therapy with chelating agents is utilized for the treatment of toxic metal intoxication. Herein we present novel information indicating that monensin (applied as tetraethylammonium salt) is a promising chelating agent for the treatment of Cd-induced renal and cardiac dysfunction. The study was performed using the ICR mouse model. Adult ICR male mice were divided into three groups with six animals in each group: control (received distilled water and food ad libitum for 28 days); Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from day 1 to day 14 of the experimental protocol), and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for 2 weeks). Cd intoxication of the animals resulted in an increase of the organ weight/body weight indexes. Cd elevated significantly creatinine and glucose level in serum. Monensin treatment improved the organ weight/body weight ratios. The therapy of the Cd-intoxicated animals with monensin ameliorated the creatinine and glucose level in serum and decreased the concentration of the toxic metal ions in the heart and kidneys by 54 % and 64 %, respectively


2000 ◽  
Vol 68 (6) ◽  
pp. 3153-3157 ◽  
Author(s):  
Christian Østergaard ◽  
Runa Vavia Yieng-Kow ◽  
Thomas Benfield ◽  
Niels Frimodt-Møller ◽  
Frank Espersen ◽  
...  

ABSTRACT The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ∼106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively;P < 0.02). A less consistent decrease in CSF TNF-α levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively;P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-α into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.


2009 ◽  
Vol 24 (5) ◽  
pp. 383-386 ◽  
Author(s):  
Cecília Maria de Carvalho Xavier Holanda ◽  
Monique Batista da Costa ◽  
Natália Chilinque Zambão da Silva ◽  
Maurício Ferreira da Silva Júnior ◽  
Vanessa Santos de Arruda Barbosa ◽  
...  

PURPOSE: Aloe vera is a tropical plant popularly known in Brazil as babosa. We have investigated the effect of aqueous extract of Aloe vera on the biodistribution of Na99mTcO4 and laboratorial parameters in Wistar rats. METHODS: Twelve animals were divided into treated and control groups. In the treated group, Aloe vera was given by gavage (5mg/mL/day) during 10 days. The control group received sorbitol by the same way and period. One hour after the last dose, we injected 0.1mL of Na99mTcO4 by orbital plexus. After 60 min, all the animals were killed. Samples were harvested from the brain, liver, heart, muscle, pancreas, stomach, femur, kidneys, blood, testis and thyroid and the percentage of radioactivity (%ATI/g) was determined. Biochemical dosages were performed. RESULTS: There was a significant increase of %ATI/g in blood, femur, kidneys, liver, stomach, testis and thyroid and also in blood levels of AST and ALT. A significant decrease in levels of glucose, cholesterol, triglycerides, creatinine and urea occurred. The statistical analyses were performed by Mann-Whitney test and T-Student test (p<0.05). CONCLUSION: The aqueous extract of Aloe vera facilitated the uptake of Na99mTcO4 in organs of rats and it was responsible to a high increase of levels of AST and ALT.


2016 ◽  
Vol 11 (1) ◽  
pp. 212 ◽  
Author(s):  
Saudy Saret Pablo-Pérez ◽  
María Mirian Estévez-Carmona ◽  
María Estela Meléndez-Camargo

<p class="Abstract">The aim of this study was to evaluate the diuretic activity of <em>Eysenhardtia polystachya</em> bark aqueous extract at different doses in a rat model. Different doses of <em>E. polystachya</em> (125, 250, 500 and 750 mg/kg body weight), furosemide (4 mg/kg) and vehicle were administered per os to female rats (n=6 animals per group). After 6 hours in metabolic cages, the effect on urinary flow, glomerular filtration rate and electrolyte balance of sodium and potassium were assessed in all animals. <em>E. polystachya</em> at the doses of 500 and 750 mg/kg induced diuretic activity, since markedly increased (p&lt;0.05) the urinary flow rate, similar to that of furosemide treated group. Only the dose of 750 mg/kg produced an increment in urinary excretion of sodium but not of potassium compared with control group. These findings indicate that<em> E. polystachya</em> bark-induced diuretic activity, providing evidence for its folkloric use.</p><p> </p>


2015 ◽  
Vol 35 (4) ◽  
pp. 398-403 ◽  
Author(s):  
Y Alcaraz-Contreras ◽  
RP Mendoza-Lozano ◽  
ER Martínez-Alcaraz ◽  
M Martínez-Alfaro ◽  
MA Gallegos-Corona ◽  
...  

We studied the effect of silymarin and dimercaptosuccinic acid (DMSA), a chelating agent that was administered individually or in combination against lead (Pb) toxicity in rats. Wistar rats (200 ± 20) were randomly divided into five groups. Group A served as a control. Groups B–E were exposed to 2000 ppm of lead acetate in drinking water for 8 weeks. Group B served as a positive control. Group C received silymarin (100 mg kg−1 orally) for 8 weeks. Group D received DMSA (75 mg kg−1 orally) once daily for the last 5 days of treatment. Group E received DMSA and silymarin as groups C and D, respectively. The effect of Pb was evaluated and accordingly the treatments on blood lead levels (BLLs), renal system, and genotoxic effects were calculated using comet assay. The BLLs were significantly increased following the exposition of lead acetate. The administration of silymarin and DMSA provided reduction in BLLs. Silymarin and DMSA provided significant protection on the genotoxic effect of Pb. The toxic effect of Pb on kidneys was also studied. Our data suggest that silymarin and DMSA improve the renal histopathological lesions.


2020 ◽  
Vol 20 (07) ◽  
pp. 16984-16996
Author(s):  
MMC Anyakudo ◽  
◽  
DO Adeniji ◽  

The metabolic response to nutrient ingestion and the rate of digestion and absorption of nutrient molecules in bowel physiology plays an important role in the metabolic control of some human chronic non-infectious diseases. This experimentally-controlled designed nutritional study which lasted eight weeks aimed to determine the effects of proportional high-protein/low-carbohydrate (HP/LC) formulated diet on glycemic tolerance, glycemic control, body weight, organ weight and organ morphometry in healthy and diabetic adult male Wistar rats. Twenty-four male Wistar rats purchased from a disease-free stock were randomly categorized into four groups (n = 6, each) after two weeks acclimatization period in raised stainless steel cages with 6 mm2mesh floor and replaceable numbered blotters papers placed under each cage in a well-ventilated animal house. Animal groups include: Healthy control group (HC), Healthy treated group (HT), Diabetic control group (DC) and Diabetic treated group (DT. The animals were fed according to the experimental design with water ad libitumfor eight weeks. Diabetes was inducted with freshly prepared alloxan monohydrate solution (150 mg/kg bw, intraperitoneally). Body weights and fasting blood sugar concentrations were measured twice weekly, while oral glucose tolerance test was conducted on the last day of the eighth-week study and subsequently followed by organs extraction after anesthesia for weight and gross assessment. Proportional high-protein/low-carbohydrate formulated diet caused significant reduction in mean body weight of treated diabetic (DT: 22.6%; P= .001) and healthy (HT: 5.8%; P= .007) rats while the control animals on control diet recorded significant (P< .05) increase in body weight gain (DC: 12.4%; HC: 11.2%). Glycemic tolerance and control improved significantly in diabetic treated rats over that of the healthy treated rats. Gross morphometry of the extracted organs (kidneys, liver, heart, lungs, spleen and testes) revealed sustained normal morphological features without any visible lesion. In conclusion, consumption of proportional high-protein/low-carbohydrate formulated diet enhanced body weight reduction and sustained normal organ morphological features with good glycemic tolerance and control in experimental rats, suggesting its dietary potentiality, safety and suitability to ameliorate obesity-related diabetes.


2018 ◽  
Vol 9 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Peiyu Li ◽  
Cheng Jiwu

Abstract Background This study evaluates the effect of butin against brain edema in intracerebral hemorrhage (ICH). Methodology ICH was induced by injecting bacterial collagenase in the brain and all the animals were separated into four groups such as control group, ICH group treated with vehicle, Butin 25 and 50 mg/kg group receives butin (25 and 50 mg/kg, i.p.)60 min after the induction of ICH in all animals. One day after neurological score, hemorrhagic injury and expressions of protein responsible for apoptosis and inflammatory cytokines were assessed in the brain tissue of ICH rats. Result Neurological scoring significantly increased and hemorrhagic lesion volume decreased in butin treated group of rats compared to ICH group. However, treatment with butin significantly decreases the ratio of Bax/Bcl-2 and protein expression of Cleaved caspase-3 than ICH group in dose dependent manner. Level of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) in the brain tissues were significantly decreased in the butin treated group than ICH group. In addition butin attenuates the altered signaling pathway of NF-κB in the brain tissues of ICH rats. Conclusion Our study concludes that butin attenuates the altered behavior and neuronal condition in ICH rats by reducing apoptosis and inflammatory response.


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