Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways

Dai, Chongshan; Liu, Qiangqiang; Li, Daowen; Sharma, Gaurav; Xiong, Jianli; Xiao, Xilong

doi:10.3390/biom10071010

Cited by 27 publications

(15 citation statements)

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“…The previous studies had demonstrated that oxidative stress might play a critical role in CuSO 4 -induced nephrotoxicity in vitro in kidney cell lines (i.e., HEK293 cells) and in vivo in a mouse/rat nephrotoxicity model ( 10 , 23 ). In line with these observations, lower levels of GSH and marked decreases of SOD and CAT activities were detected in the kidney tissues of mice exposed with CuSO 4 ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cu overdose could disturb this balance and induce the production of excessive ROS, which leads to lipid, protein and DNA damage ( 39 ). Previous studies demonstrated that CuSO 4 or copper chloride (CuCl 2 ) exposure can induce the production of excessive ROS in HEK293 cells, mouse liver cells or neuronal cells ( 23 , 40 , 41 ). Mitochondria are not only the major producer of cellular ROS but also a target ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…Control group mice were administered orally with equal volume of 0.5% CMC-Na (vehicle). Mice in all CuSO4 groups were administered orally with aqueous solution of CuSO4 at the dose of 200 mg/kg per day, in line with a previously published study ( 23 ). The previous studies reported that oral supplementation of quercetin in the range of 25–100 mg/kg/day for 1–4 weeks could protect against cadmium or gentamicin -induced renal toxicity in rats ( 24 , 25 ).…”

Section: Methodsmentioning

confidence: 99%

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Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

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Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

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“…A previous study revealed that CuSO 4 induces cellular ROS production in HEK293 cells. [ 20 ] Administration of CuSO 4 significantly inhibited the effect of a uniform magnetic field on PEI‐mediated transfection (Figure S2B, Supporting Information). To confirm the uniform magnetic field‐dependent enhancement of PEI‐mediated transfection in vivo, eight‐week‐old male mice were transfected with peGFP‐C1 plasmid DNA via tail vein injection and exposed to a 1.6 mT uniform magnetic field for 17 h (Figure S3A‐C, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

A novel strategy of selective gene delivery by using a uniform magnetic field

Dateki

Imamura

Arai

et al. 2021

Biotechnology Journal

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The application of a magnetic field to enhance the transfection efficiency has been reported to be mainly dependent on the magnetic force generated by a magnetic field gradient to attract paramagnetic bead-conjugated carrier and polynucleotide complexes. This strategy has the advantage of targeting a point or an area on the culture vessel. However, it is difficult to target deeply placed tissues in vivo. Uniform magnetic field-correlated effect is applicable to such a purpose. Here, we attempted to establish a novel procedure for uniform magnetic field-dependent enhancement of transfection efficiency. We examined the effect of a 1.5 mT uniform magnetic field on cellular reactive oxygen species (ROS) level and transfection efficiency mediated by a ROS-sensitive transfection carrier. Our experimental results revealed that a 1.5 mT uniform magnetic field transiently decreased cellular ROS levels and strongly enhanced transfection efficiency mediated by polyethylenimine (PEI). The uniform magnetic field-dependent enhancement of PEI-mediated in vivo transfection was confirmed in the livers of mice. Local intensification of a uniform magnetic field in a culture dish resulted in selective gene delivery into cells on the target area. Although further examination and improvement are necessary for this procedure, our findings provide a novel option for spatial control of gene delivery. K E Y W O R D S polyethylenimine, reactive oxygen species, selective gene delivery, transfection, uniform magnetic field 1 INTRODUCTION To analyze the physiological roles of the genes of interest, researchers experience growing demands for selective gene delivery. Techniques for photodynamic control of DNA/RNA delivery have become available and possess great potential for future applications in research Abbreviations: 8-OHdG, 8-hydroxy-2'-deoxyguanosine; AIPcS 2a , aluminum phthalocyanine disulfonate; CBA, cell-based assay; DAPI, 4' ,6-diamidino-2-phenylindole; eGFP, enhanced green fluorescent protein; ES, embryonic stem; N/P, nitrogen/phosphate; NAC, n-acetyl cysteine; PBS, phosphate-buffered saline; PEI, polyethylenimine; qPCR, quantitative polymerase chain reaction; qRT-PCR, quantitative reverse transcription PCR; ROS, reactive oxygen species; SEM, standard error of mean and therapy. DNA/RNA-nanocarrier complexes enter cells mainly by clathrin-mediated endocytosis. Endocytic trafficking of the complexes includes the following four stages: cell binding, endocytosis, endosomal escape, and cytosolic transit. [1] Essential for the efficient DNA/RNA delivery among these stages is the endosomal escape, which avoids lysosomal degradation. Photodynamic enhancement of endosomal escape mediated by photosensitizers and light irradiation results in large improvements in transfection efficiency. [2-7] The strategy of photodynamic enhancement has disadvantages because of poor light transmission through tissues. In contrast, magnetic fields can penetrate living organs and initiate cellular and molecular reactions. [8] It has been shown that the onset of...

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“…Similar findings were also reported by Ghanem ( 2006 Several histopathological alterations in the kidney of Tilapia spp. from Lake Qarun were recorded a severe vacuolar degeneration with hypertrophy of epithelial cells at the renal tubules, severe degeneration and necrosis in the renal tubules with focal areas of necrosis between the renal tubules, haemorrhage, haemolysis and aggregations of inflammatory cells between the renal tubules, depletion in the haemopoietic areas, dilation of the tubular lumen, edema in Bowman's capsules with atrophy in the glomeruli as well as dilation and congestion in renal blood vessels Mohamed, 2019;Dai et al, 2020 ).…”

Section: Histopathological Studies: 21 Kidneys Histopathologymentioning

confidence: 99%

Effect of bioaccumulation and biosedimentation of some heavy metals on histological features in the cichlid fish, Tilapia zillii inhabiting Lake Qarun, Egypt.

Elwasify¹

2021

Egypt. J. of Aquatic Biolo. and Fish.

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Lake Qarun constitutes one of the very important sectors in the Egyptian fisheries. It is a closed elongated marine lake with irregular shape (Figure 1). Lake Qarun contains different species of fish and is considered one of the most important wintering and nesting sites for many species of the migratory birds. It is approximately 55000 feddans (22000 hectares) or approximately 107 square kilometers (

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Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways

Cited by 27 publications

References 58 publications

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

A novel strategy of selective gene delivery by using a uniform magnetic field

Effect of bioaccumulation and biosedimentation of some heavy metals on histological features in the cichlid fish, Tilapia zillii inhabiting Lake Qarun, Egypt.

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