Low-dose cadmium activates the JNK signaling pathway in human renal podocytes

Chen, Jiayao; Xu, Yi; Cheng, Zuowang; Hong, Soon-Kwang; Liu, Xiu; Xu, Dongmei; Kapron, Carolyn M.; Liu, Ju

doi:10.3892/ijmm.2018.3445

Cited by 3 publications

(3 citation statements)

References 44 publications

(50 reference statements)

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“…Several studies have been found the activation of c-Jun N-terminal Kinase (JNK) in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [ 38 , 39 ]. Recent and previous studies suggested that Cd activates the p-JNK signaling pathway and leads to neuronal apoptosis [ 40 ]. Therefore, we examined the expression level of p-JNK via Western blot and confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain

Alam

Kim

Shah

et al. 2021

Cells

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Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2. Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2. Moreover, ALA suppressed CdCl2-induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1β (IL-1β) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.

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Section: Resultsmentioning

confidence: 99%

Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain

Alam

Kim

Shah

et al. 2021

Cells

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“…Food and cigarettes are two major sources of human exposure to Cd (Mannino et al, 2004;Ivanova et al, 2017); however, higher levels of exposure to Cd may be seen in occupational settings, such as nickel-cadmium battery manufacturing enterprises. Cd is associated with severe damage to various organs including kidney, liver, brain, bone, testicles, and the cardiovascular system (Wang et al, 2017;Chen et al, 2018b;Zhang and Reynolds, 2019). Kidney is one of the primary organs targeted by Cd (Chen et al, 2016;Jarup and Akesson, 2009), and Cd is effectively retained in kidney tissue with concentrations directly proportional to those in urine (Mallya et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia exacerbates cadmium-induced glomerular nephrosis

Liu

Zhang

2021

Toxicol Ind Health

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Current research suggests that cadmium (Cd) exposure may be associated with the progression of diabetic nephropathy; however, the details of this relationship are insufficiently understood. The present study investigated the effects of elevated glucose on Cd-induced toxicity to glomerular cells using in vitro and in vivo models, and it demonstrated that Cd exposure and the hyperglycemia of diabetes acting together increased the risk of developing glomerular nephrosis . In vitro, human podocytes were exposed to a DMEM low-glucose media without (control), or with Cd (as CdCl2), or a high-glucose media plus Cd. The CCK-8, ROS, apoptosis, and mitochondrial transmembrane potential (ΔΨm) assays showed that human podocytes exposed to Cd in a high-glucose media had greater degrees of injury compared with cells treated with Cd at low (euglycemic)-glucose levels. In vivo, diabetic hyperglycemia was induced by streptozotocin in 8-week-old male C57BL/6 mice to which either CdCl2 or saline (control) was intraperitoneally injected twice weekly for 24 weeks. Compared with euglycemic saline-treated controls, the diabetic mice exposed to Cd demonstrated decreased body weight and increased blood urea nitrogen levels along with histopathological renal architecture changes including collagen fiber accumulation. The results of this study supported the hypothesis that hyperglycemia plus Cd exposure increases the risk of damage to glomerular podocytes compared with Cd exposure in euglycemia.

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“…Some researchers speculate that genome instability and DNA damage may sometimes result from Cd toxicity, resulting in malignancy [ 10 , 40 , 63 , 64 ]. Correction of inaccurate base pairs, deletion of unrequired base pairs, and repair of damaged pairs are usually blocked by Cd via the recognition of damaged DNA and attachment of proteins to affected sites [ 10 , 40 , 65 , 66 ]. Our results are in accordance with those studies.…”

Section: Discussionmentioning

confidence: 99%

Damage to the Testicular Structure of Rats by Acute Oral Exposure of Cadmium

Iqbal

Cao

Zhao

et al. 2021

IJERPH

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Cadmium (Cd) is one of the most important heavy metal toxicants, used throughout the world at the industrial level. It affects humans through environmental and occupational exposure and animals through the environment. The most severe effects of oral exposure to Cd on the male reproductive system, particularly spermatogenesis, have not been discussed. In this study, we observed the damage to the testes and heritable DNA caused by oral exposure to Cd. Adult male Sprague–Dawley rats were divided into four groups: a control group and three groups treated with 5, 10, and 15 mg Cd/kg/day for 17 days by oral gavage. Our results revealed that Cd significantly decreases weight gain in 10 and 15 mg/kg groups, whereas the 5 mg/kg groups showed no difference in weight gain. The histopathology showed adverse structural effects on the rat testis by significantly reducing the thickness of the tunica albuginea, the diameter of the tubular lumen, and the interstitial space among seminiferous tubules and increasing the height of the epithelium and the diameter of the seminiferous tubules in Cd treated groups. Comet assay in epididymal sperms demonstrated a significant difference in the lengths of the head and comet in all the 3 Cd treated groups, indicating damage in heritable DNA, although variations in daily sperm production were not significant. Only a slight decrease in sperm count was reported in Cd-treated groups as compared to the control group, whereas the tail length, percentage of DNA in head, and tail showed no significant difference in control and all the experimental groups. Overall, our findings indicate that Cd toxicity must be controlled using natural sources, such as herbal medicine or bioremediation, with non-edible plants, because it could considerably affect heritable DNA and induce damage to the reproductive system.

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Low-dose cadmium activates the JNK signaling pathway in human renal podocytes

Cited by 3 publications

References 44 publications

Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain

Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain

Hyperglycemia exacerbates cadmium-induced glomerular nephrosis

Damage to the Testicular Structure of Rats by Acute Oral Exposure of Cadmium

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