title: Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro.
abstract: Radiocontrast-induced nephropathy (RIN) is one of the leading causes of hospital-acquired acute kidney injury (AKI). The clinical strategies currently available for the prevention of RIN are insufficient. In this study, we aimed to determine whether resveratrol, a polyphenol phytoalexin, can be used to prevent RIN. For this purpose, in vitro experiments were performed using a human renal proximal tubule epithelial cell line (HK-2 cells). Following treatment for 48 h, the highly toxic radiocontrast agent, ioxitalamate, exerted cytotoxic effects on the HK-2 cells in a concentration-dependent manner, as shown by MTT assay. The half maximal inhibitory concentration (IC50) was found to be approximately 30 mg/ml. Flow cytometry also revealed a marked increase in the number of apoptotic cells following exposure to ioxitalamate. In addition, the number of necrotic, but not necroptotic cells was increased. However, treatment with resveratrol (12.5 µM) for 48 h significantly alleviated ioxitalamate (30 mg/ml)-induced cytotoxicity, by reducing cytosolic DNA fragmentation, increasing the expression of the anti-apoptotic protein, Bcl-2 (B-cell lymphoma 2), and survivin, activating caspase-3, preventing autophagic death and suppressing the production of reactive oxygen species (ROS). Resveratrol also suppressed the ioxitalamate-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage. N-acetylcysteine (NAC), a ROS scavenger commonly used to prevent RIN, also reduced ioxitalamate-induced cytotoxicity, but at a high concentration of 1 mM. Sirtuin (SIRT)1 and SIRT3 were not found to play a role in these effects. Overall, our findings suggest that resveratrol may prove to be an effective adjuvant therapy for the prevention of RIN.
authors.affiliation: Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Yen Ta
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Master Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Yi Ya
authors.initials: YY
authors.lastname: Chen
authors.affiliation: PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Yu Hsien
authors.initials: YH
authors.lastname: Lai
authors.affiliation: Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.
authors.forename: Chuan Chu
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.
authors.forename: Tzu Chun
authors.initials: TC
authors.lastname: Lin
authors.affiliation: PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Ying Shih
authors.initials: YS
authors.lastname: Su
authors.affiliation: Department of Pharmacology, College of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Chin Hung
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Pei Chun
authors.initials: PC
authors.lastname: Lai
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007483:Iothalamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D003287:Contrast Media; D017382:Reactive Oxygen Species; D013267:Stilbenes; D007483:Iothalamic Acid; C002587:ioxitalamic acid; D000077185:Resveratrol