Expression of 8-hydroxydeoxyguanosine in Nephrolithiatic Renal Tissues and Toxicity of Calcium Oxalate Monohydrate to Human Kidney Cell Line
Keywords:calcium oxalate monohydrate, oxidative stress, reactive oxygen species, 8-hydroxydeoxyguanosin
Objective: To explore expression of 8-hydroxydeoxyguanosine (8-OHdG, a marker of oxidative DNA damage) in renal tissues obtained from calcium oxalate nephrolithiasis patients, and to investigate the effects of calcium oxalate monohydrate (COM) crystals on viability of human proximal renal tubular cells (HK-2) and intracellular reactive oxygen species (ROS) production.
Design: Observational analytical study.
Methods: Expression of 8-OHdG in paraffin-embedded nephrolithiatic renal sections (n=10) was explored by immunohistochemical staining. MTT assay was used to assess viability of HK-2 cells after exposed to COM in both dose and time-dependent experiments. The effect of COM on intracellular ROS production in HK-2 cells was determined using dichlorofluorescein method.
Results: In stone-containing renal tissues, 8-OHdG was strongly expressed in renal tubular cells. There was no expression of 8-OHdG in normal renal tissues. COM decreased viability of HK-2 cells in both dose- and time-dependent maners. Intracellular ROS generation was increased in HK-2 cells after treated with COM.
Conclusions: 8-OHdG was overexpressed in the kidneys of nephrolithiasis patients suggested that oxidative stress involved in the progress of kidney stone disease. COM was injurous to renal tubular cells. A decreased cell survival after treatment with COM may be mediated via ROS toxicity. Attenuation of oxidative damage by antioxidants is recommended for medical management of stone patietns.
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