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Nature Neuroscience Sep 2013The lack of therapies for progressive multiple sclerosis highlights the need to understand the regenerative process of remyelination that can follow CNS demyelination....
The lack of therapies for progressive multiple sclerosis highlights the need to understand the regenerative process of remyelination that can follow CNS demyelination. This involves an innate immune response consisting of microglia and macrophages, which can be polarized to distinct functional phenotypes: pro-inflammatory (M1) and anti-inflammatory or immunoregulatory (M2). We found that a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started. Oligodendrocyte differentiation was enhanced in vitro with M2 cell conditioned media and impaired in vivo following intra-lesional M2 cell depletion. M2 cell densities were increased in lesions of aged mice in which remyelination was enhanced by parabiotic coupling to a younger mouse and in multiple sclerosis lesions that normally show remyelination. Blocking M2 cell-derived activin-A inhibited oligodendrocyte differentiation during remyelination in cerebellar slice cultures. Thus, our results indicate that M2 cell polarization is essential for efficient remyelination and identify activin-A as a therapeutic target for CNS regeneration.
Topics: Adult; Aged; Aged, 80 and over; Animals; Animals, Newborn; Cadmium Chloride; Cell Differentiation; Cells, Cultured; Central Nervous System; Clodronic Acid; Culture Media, Conditioned; Demyelinating Diseases; Female; Humans; In Vitro Techniques; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Middle Aged; Myelin Proteins; Oligodendroglia; Rats; Rats, Sprague-Dawley; Regeneration
PubMed: 23872599
DOI: 10.1038/nn.3469 -
Comparative Biochemistry and... Jun 2023Fish in wild are often faced with various types of xenobiotics, that may display synergistic or antagonistic effects. In this study, we aim to examine how exposure to...
Fish in wild are often faced with various types of xenobiotics, that may display synergistic or antagonistic effects. In this study, we aim to examine how exposure to agrochemical compound (Bacilar) and cadmium (CdCl) alone and in combination affect biochemical parameters (lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase; creatine phosphokinase (CKP), cholinesterase) and oxidative stress (total antioxidant capacity, catalase, malondialdehyde and protein carbonyl concentrations) of freshwater fish Alburnus mossulensis. Fish were exposed to two concentrations of Bacilar (0.3, and 0.6 mL L) and to 1 mg L cadmium chloride alone and in combination for 21 days. Results showed that fish accumulate Cd in their body, with the highest rate in individuals exposed to Cd in combination with Bacilar. Both xenobiotics in fish liver induced the activation of liver enzymes suggesting hepatotoxic effects, with the greatest impact in co-exposed groups. A significant decrease in the hepatocyte's total antioxidant capacity indicates the collapse of the antioxidant defense in fish exposed to Cd and Bacilar. A decrease in the antioxidant biomarkers was followed by increased oxidative damage of lipids and proteins. We also reported altered function in the muscle of individuals exposed to Bacilar and Cd seen as decreased activities in CKP and butyrylcholinesterase. Overall, our results point to the toxicity of both Bacilar and Cd on fish but also to their synergistic effects on Cd bioaccumulation, oxidative stress, and liver and muscle damage. This study highlights the need for evaluating the use of agrochemicals and their possible additive effects on non-target organisms.
Topics: Animals; Antioxidants; Cadmium Chloride; Cadmium; Butyrylcholinesterase; Oxidative Stress; Fishes; Liver; Fresh Water
PubMed: 36940894
DOI: 10.1016/j.cbpc.2023.109614 -
Toxins Mar 2021Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than...
Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than one type of food contaminant by consumers may take place, which provides a strong rationale for investigating the combined toxicities of these food contaminants. Patulin is one of the most common food-borne mycotoxins, whereas cadmium is a representative of toxic heavy metals found in food. The liver and kidneys are the main target organ sites for both patulin and cadmium. We hypothesized that simultaneous exposure to patulin and cadmium could produce synergistic hepatotoxicity and nephrotoxicity. Alpha mouse liver 12 (AML12) and Human embryonic kidney (HEK) 293 (HEK293) cell lines together with a mouse model were used to explore the combination effect and mechanism. The results demonstrated, for the first time, that the co-exposure of liver or renal cells to patulin and cadmium caused synergistic cytotoxicity in vitro and enhanced liver toxicity in vivo. The synergistic toxicity caused by the co-administration of patulin and cadmium was attributed to the boosted reactive oxygen species (ROS) generation. c-Jun N-terminal kinase 1 (JNK1) and p53 as downstream mediators of oxidative stress contributed to the synergistic toxicity by co-exposure of patulin and cadmium, while p53/JNK1 activation promoted the second-round ROS production through a positive feedback loop. The findings of the present study extend the toxicological knowledge about patulin and cadmium, which could be beneficial to more precisely perform risk assessments on these food contaminants.
Topics: Animals; Apoptosis; Cadmium Chloride; Chemical and Drug Induced Liver Injury; Drug Synergism; Food Contamination; HEK293 Cells; Humans; Kidney; Kidney Diseases; Liver; Male; Mice; Mice, Inbred C57BL; Mitochondria; Mitogen-Activated Protein Kinase 8; Oxidative Stress; Patulin; Reactive Oxygen Species; Tumor Suppressor Protein p53
PubMed: 33803748
DOI: 10.3390/toxins13030221 -
Data in Brief Aug 2022This dataset demonstrates the in vivo renal histology and biochemical activity of Atorvastatin (AT) in cadmium-induced nephrotoxic rat model. Fifty-six adult male Wistar...
This dataset demonstrates the in vivo renal histology and biochemical activity of Atorvastatin (AT) in cadmium-induced nephrotoxic rat model. Fifty-six adult male Wistar rats assigned to eight groups. Rats were treated with physiologic saline at a volume of 4 mg/kg, contained Atorvastatin at a dose of 20 mg/kg body weight for 15 days. The intraperitoneal administration of cadmium chloride at doses of 1, 2, 1 and 3 mg/kg started on day 8. On day 16, samples were collected for biochemical and histological analyses. Data of renal function were estimated in the serum and organ. Cadmium chloride increased malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) serum level and decreased superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) levels. Administration of Atorvastatin significantly increased lipid peroxidation and renal decreased glutathione and antioxidant enzymes activity and significantly decreased BUN and Creatinine levels. Data were supported by histological examination indicated improved changes and kidney protective potential following cadmium chloride-induced oxidative stress.
PubMed: 35789907
DOI: 10.1016/j.dib.2022.108394 -
JBRA Assisted Reproduction Apr 2021Xylopia aethiopica is a common plant in West Africa, with wide applications in trado-medical management of several diseases. Thus, our study aimed to analyze the...
OBJECTIVE
Xylopia aethiopica is a common plant in West Africa, with wide applications in trado-medical management of several diseases. Thus, our study aimed to analyze the histology and hormonal effects of ethanol extracts of Xylopia aethiopica seeds on cadmium chloride-induced reproductive dysfunction in female Wistar rats.
METHODS
We used twenty-five rats weighing 120-150g for this study. The rats were divided into five groups (n=5). Group 1: received only distilled water orally; Group 2: received 2 mg/kg cadmium chloride orally; Group 3: received 2 mg/kg cadmium chloride plus 50 mg/kg Xylopia aethiopica seeds orally; Group 4: received 2 mg/kg cadmium chloride plus 100 mg/kg Xylopia aethiopica seeds orally, and Group 5: received 100 mg/kg Xylopia aethiopica seeds only, orally. We administered the extracts for 14 days, after which we slaughtered the animals following chloroform anesthesia. We took the blood samples by cardiac puncture for hormonal assay. The ovaries and uterus were harvested for histology. We analyzed the data using ANOVA, and the differences in mean values were considered significant at p<0.05.
RESULTS
The body weight of the rats showed a dose-dependent reduction (p<0.05), compared with the controls. Xylopia aethiopica seeds significantly (p<0.05) reversed the detrimental effects of Cadmium on LH and FSH. The histological analysis of the ovary showed significant improvement upon treatment with Xylopia aethiopica extract in a dose-dependent manner.
CONCLUSIONS
The ameliorative effects of Xylopia aethiopica against cadmium chloride-induced reproductive toxicity in female Wistar rats may be attributed to its antioxidant properties.
Topics: Animals; Cadmium Chloride; Ethanol; Fruit; Gonadotropins; Ovary; Plant Extracts; Rats; Rats, Wistar; Xylopia
PubMed: 33507724
DOI: 10.5935/1518-0557.20200091 -
Ecotoxicology and Environmental Safety May 2022Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to...
Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 μM were selected to evaluate the mitochondrial toxicity of CdCl respectively. Under the CdCl treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 μM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 μM concentration compared with no CdCl treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl.
Topics: Apoptosis; Cadmium; Cadmium Chloride; Electron Transport; Humans; Membrane Potential, Mitochondrial; Oxidative Stress; Reactive Oxygen Species
PubMed: 35413622
DOI: 10.1016/j.ecoenv.2022.113494 -
Archives of Razi Institute Feb 2022Adult males are considered the main causes of infertility defects in the world; therefore, scientists are searching for factors that play a role in male fertility, such...
Adult males are considered the main causes of infertility defects in the world; therefore, scientists are searching for factors that play a role in male fertility, such as kisspeptin, which acts as one of the master controllers and regulators of gonadotropin secretion from the hypothalamus in mammalian species. Furthermore, it has been shown that the kisspeptin receptor is mainly localized in the interstitial and germ cells of the testicles and has a role in the regulation of gonadal development and function. This study aimed to investigate the effect of kisspeptin on testicular degeneration syndrome induced by cadmium chloride in male Wistar rats and identify the best concentration of kisspeptin to cure this syndrome. A total of 40 male rats were divided into four equal groups of negative control (n=10) that was injected subcutaneously (SC) with normal saline solution twice a week for 42 days; positive control (n=10) that was intraperitoneally injected with cadmium chloride (1 mg/kg B.W., once a week for two weeks); T that was intraperitoneally injected with cadmium chloride (1 mg/kg B.W., once a week for two weeks), and after 14 days, 20 nmol/rat of kisspeptins were injected SC twice a week for 42 days in all animals; and T that was intraperitoneally injected with cadmium chloride (1 mg/kg B.W. once a week for two weeks), and after 14 days, 40 nmol/rat of kisspeptins were injected SC twice a week for 42 days in all animals. All animals were then euthanized after 42 days, and their testes were dissected for a histological study. The results of the present study confirmed that cadmium chloride affected the male testes and sperm parameters, while the administration of kisspeptin at doses of 20 and 40 nmol/rat (twice a week) by SC injection showed a significant effect in restoring the reproduction feature and histology of the rats' testicular tissue.
Topics: Animals; Cadmium Chloride; Kisspeptins; Male; Rats; Rats, Wistar; Semen; Testis
PubMed: 35891723
DOI: 10.22092/ARI.2021.356811.1918 -
Oncology Reports Aug 2020Osteosarcoma is a highly malignant disease and is associated with a poor patient prognosis and a high mortality rate. Disease prognosis significantly correlates with...
Osteosarcoma is a highly malignant disease and is associated with a poor patient prognosis and a high mortality rate. Disease prognosis significantly correlates with chemotherapeutic responses. Cadmium is a heavy metal with specific effects on bone, but its benefits for osteosarcoma treatment have not been characterized. In the present study, cadmium chloride was used to treat MG63 osteosarcoma cells, and their gene expression profiles were assessed by GeneChip technology. We found that forkhead box protein M1 (FOXM1) was downregulated by cadmium chloride, and lentiviral‑mediated silencing of FOXM1 confirmed a role for this factor in the cisplatin resistance of MG63 cells. In nude mice, cadmium chloride enhanced the sensitivity of osteosarcoma to cisplatin, an effect mediated by FOXM1. Collectively, these data indicate that cadmium chloride can alter the sensitivity of osteosarcoma cells to cisplatin through FOXM1, highlighting it as a potential therapeutic target and prognostic factor for osteosarcoma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Cadmium Chloride; Cell Line, Tumor; Cisplatin; Down-Regulation; Drug Resistance, Neoplasm; Forkhead Box Protein M1; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Mice; Osteosarcoma; Xenograft Model Antitumor Assays
PubMed: 32627005
DOI: 10.3892/or.2020.7632 -
Annals of Medicine Dec 2021Suppressed glucose metabolism, elevated fatty acid metabolism and lipid deposition within myocardial cells are the key pathological features of diabetic cardiomyopathy....
CONTEXT
Suppressed glucose metabolism, elevated fatty acid metabolism and lipid deposition within myocardial cells are the key pathological features of diabetic cardiomyopathy. Studies have associated cadmium exposure with metabolic disturbances.
OBJECTIVE
To examine the effects of cadmium exposure on cardiac glucose homeostasis and lipid accumulation in male Wistar rats.
METHODS
Male Wistar rats were treated for 21days as (=5): Control, cadmium chloride Cd5 (5mg/kg, ), cadmium chloride Cd30 (30mg/kg, ).
RESULTS
The fasting serum insulin level in this study decreased significantly. Pyruvate and hexokinase activity reduced significantly in the Cd5 group while no significant change in lactate and glycogen levels. The activity of pyruvate dehydrogenase enzyme significantly increased with an increasing dosage of cadmium. The free fatty acid, total cholesterol and triglyceride levels in the heart increased significantly with increasing dosage of cadmium when compared with the control. Lipoprotein lipase activity in the heart showed no difference in the Cd5 group but a reduction in the activity in the Cd30 group was observed.
CONCLUSION
This study indicates that cadmium exposure interferes with cardiac substrate handling resulting in impaired glucometabolic regulation and lipid accumulation which could reduce cardiac efficiency.
Topics: Animals; Cadmium; Cadmium Chloride; Glucose Tolerance Test; Humans; Insulin; Lipid Metabolism; Lipids; Male; Myocardium; Oxidoreductases; Pyruvates; Rats; Rats, Wistar
PubMed: 34259114
DOI: 10.1080/07853890.2021.1947519 -
International Journal of Environmental... Jan 2016Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic...
Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium. Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG₂) cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet) assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay). The result of MTT assay indicated that cadmium chloride induces toxicity to HepG₂ cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05) increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG₂ cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05) was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG₂) cells.
Topics: Apoptosis; Cadmium Chloride; Cell Survival; Comet Assay; DNA Damage; Environmental Pollutants; Hep G2 Cells; Humans; Oxidative Stress
PubMed: 26729151
DOI: 10.3390/ijerph13010088