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Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress

Abstract

Arsenic trioxide (As2O3) is an environmental toxicant and a potent antineoplastic agent. Exposure to arsenic causes renal cancer. Resveratrol is a well-known polyphenolic compound that is reported to reduce As2O3-induced cardiotoxicity. The present study aimed to investigate the effect of resveratrol on As2O3-induced nephrotoxicity and arsenic metabolism. Chinese Dragon-Li cats were injected with 1 mg/kg As2O3 on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As2O3 treatment. On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney. Urine samples were taken for arsenic speciation. In the resveratrol + As2O3-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased. The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As2O3-treated group. These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As2O3-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As2O3 metabolism. These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity.

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Abbreviations

8-OHdG:

8-Hydroxy-2′-deoxyguanosine

As2O3 :

Arsenic trioxide

As (III):

Arsenite

As (V):

Arsenate

BUN:

Blood urea nitrogen

CAT:

Catalase

CREA:

Serum creatinine

DMA:

Dimethylated arsenic

GPX:

Glutathione peroxidase

GSH:

Glutathione

GSSG:

Glutathione disulfide

MDA:

Malondialdehyde

MMA:

Monomethylated arsenic

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

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Acknowledgments

We thank the National Science Foundation Committee of China (31101868), Heilongjiang Province Foundation for Young Scholars (QC2010057), Special Foundation of China. Postdoctoral Science Foundation (2012T50302), Chinese Postdoctoral Science Foundation (20100481040), and Heilongjiang Province Postdoctoral Science Foundation (LBH-Z10256).

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Zhigang Zhang.

Additional information

Meiling Yu and Jiangdong Xue contributed equally to this work.

Northeast Agricultural University and Inner Mongolia University for Nationalities have contributed equally in the study.

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Yu, M., Xue, J., Li, Y. et al. Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress. Arch Toxicol 87, 1025–1035 (2013). https://doi.org/10.1007/s00204-013-1026-4

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  • DOI: https://doi.org/10.1007/s00204-013-1026-4

Keywords

  • Arsenic trioxide
  • Resveratrol
  • Arsenic metabolism
  • Oxidative stress
  • Nephroprotective effect