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Increased oxidative DNA damage seen in renal biopsies adjacent stones in patients with nephrolithiasis

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Abstract

Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, is significantly higher in nephrolithiasis patients than in healthy individuals, indicating that these patients have higher degree of oxidative stress. In the present study, we investigated 8-OHdG expression in renal biopsies of patients with nephrolithiasis and in renal tubular cells (HK-2 cells) exposed to calcium oxalate monohydrate (COM). We performed immunohistochemical staining for 8-OHdG in renal biopsies adjacent stones obtained from 28 patients with nephrolithiasis. Controls were noncancerous renal tissues from nephrectomies of patients with renal cancer. 8-OHdG was overexpressed in the nucleus of renal tubular cells in patients with nephrolithiasis compared with controls. Only one nephrolithiasis biopsy was negative for 8-OHdG, whereas in 19 cases 8-OHdG was highly expressed. The level of expression of 8-OHdG among patients with calcium oxalate (mostly mixed with calcium phosphate) and uric acid stones was not significantly different. Increased leukocyte infiltration was observed in renal tissues from patients with nephrolithiasis. Exposure of HK-2 cells to COM caused increased intracellular reactive oxygen species and nuclear expression of 8-OHdG. To our knowledge, this is the first report of increased 8-OHdG expression in renal tubular cells of patients with nephrolithiasis. In vitro, COM crystals were capable of inducing oxidative damage of DNA in the proximal renal tubular cells.

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Acknowledgments

U.W. received a 72nd Birthday Anniversary of His Majesty the King’s Scholarship from Chulalongkorn University (Ratchadaphiseksomphot Endowment Fund). We are grateful for the assistance of the Biochemistry and Molecular Biology of Metabolic Diseases Research Unit.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Wipawee Kittikowit & Preecha Ruangvejvorachai

  2. Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Uraiwan Waiwijit, Chanchai Boonla & Piyaratana Tosukhowong

  3. Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Chaowat Pimratana & Chagkrapan Predanon

  4. Unit of Urology, Surgical Department, Khon Kaen Hospital, Khon Kaen, 40000, Thailand

    Supoj Ratchanon

Authors
  1. Wipawee Kittikowit
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  2. Uraiwan Waiwijit
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  3. Chanchai Boonla
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  4. Preecha Ruangvejvorachai
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  8. Piyaratana Tosukhowong
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Correspondence to Piyaratana Tosukhowong.

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Kittikowit, W., Waiwijit, U., Boonla, C. et al. Increased oxidative DNA damage seen in renal biopsies adjacent stones in patients with nephrolithiasis. Urolithiasis 42, 387–394 (2014). https://doi.org/10.1007/s00240-014-0676-x

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  • DOI: https://doi.org/10.1007/s00240-014-0676-x

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