| Mechanism of Amelioration of Cisplatin Nephrotoxicity by Procaine Treatment in Mice. |
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Do Whan Ahn, Sang Rae Kim, Dong Ho Ha, Se Hwan Kim |
1Departments of Physiology, Kosin University College of Medicine, Busan, Korea.
2Departments of Anesthesiology and Pain Medicine, Kosin University College of Medicine, Busan, Korea. kshwan@ns.kosinmed.or.kr |
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| Abstract |
BACKGROUND
Procaine binds to DNA and reduces cisplatin nephrotoxicity, but the mechanism is poorly understood. We explored whether procaine amelioration of cisplatin nephrotoxicity was related to down-and/or up-regulation of inflammatory response gene tumor necrosis factor-alpha (TNF-alpha), oxidative stress indicator gene heme oxygenase-1 (HO-1) or cell cycle inhibitor gene p21.
METHODS
Cisplatin and procaine were intraperitoneally injected to mice at a single dosage of 16 and 80 mg/kg, respectively. Renal evaluation was performed 72 hours after cisplatin administration. The expression of transcripts and proteins was analyzed using real time RT-PCR and Western blot, respectively.
RESULTS
Procaine treatment moderately attenuated necrotic changes of renal proximal tubules and increases in BUN and creatinine concentration by cisplatin administration. Kidney platinum level between the cisplatin (cis) group and the cisplatin + procaine (CisPro) group was not different.
Although the level of TNF-alpha mRNA increased 4-fold higher in the Cis group than in the control, this increase was not attenuated by procaine treatment. Gene expression of p21 and HO-1 was elevated 175 and 4-times higher in the Cis group than in the control, respectively. But their expression was no further elevated, rather significantly reduced in the CisPro group compared to the Cis group. Protein abundance of p21 and HO-1 was paralleled by their respective mRNA expression.
CONCLUSIONS
Procaine amelioration of cisplatin nephrotoxicity is likely to be achieved through processes other than the regulation of TNF-alpha, HO-1 or p21 gene expression. |
| Key Words:
cisplatin nephrotoxicity; heme oxygenase-1; procaine; tumor necrosis factor-alpha; p21 |
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