J Korean Med Sci.  2009 Jan;24(Suppl 1):S170-S175. 10.3346/jkms.2009.24.S1.S170.

Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

• Lee DW
• Kwak IS
• Lee SB
• Song SH
• Seong EY
• Yang BY
• Lee MY
• Sol MY

• KMID: 1778158
• DOI: http://doi.org/10.3346/jkms.2009.24.S1.S170

Abstract

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.

Keyword

Kidney Failure, Acute; Cisplatin; Erythropoietin; Nordihydroguaiaretic Acid

MeSH Terms

Animals
Arachidonate 5-Lipoxygenase/administration & dosage
Blood Urea Nitrogen
Cisplatin/*toxicity
Creatinine/urine
Epithelial Cells/drug effects
Erythropoietin/administration & dosage/*therapeutic use
Kidney/metabolism
Kidney Failure, Acute/*chemically induced/*drug therapy
Kidney Tubules/drug effects
Male
Nordihydroguaiaretic Acid/*therapeutic use
Rats
Rats, Sprague-Dawley
Regeneration

Figure

• 

  Fig. 1 Changes of mean serum and 24 hr urine parameters in the four groups. (A) Significant reductions in BUN levels were observed in the Cisplatin+NDGA and Cisplatin+EPO groups between Day 4 and Day 10. (B) Significant serum creatinine decreases were observed in the Cisplatin+NDGA and Cisplatin+EPO groups between Day-4 and Day-10. (C) Significant creatinine clearance increases were observed in the Cisplatin+EPO group between Day-4 and Day-10. (D) Significant Na concentration increases in urine were observed in the Cisplatin+NDGA group between Day-4 and Day-10. *p<0.05 vs. Cisplatin group. Normal controls (dashed line,○), Cisplatin (□), Cisplatin+NDGA (•), Cisplatin+EPO (♦).

• 

  Fig. 2 Histological aspects of the rat corticomedullary junction 10 days after cisplatin administration showing tubular epithelial cell swelling, vacuolization, necrosis, and desquamation affecting primarily the proximal tubule. NDGA and EPO did not modify the effects of cisplatin on renal histology (×400, PAS).

• 

  Fig. 3 PCNA-positive cells in Cisplatin+NDGA group. PCNA staining showing large nuclei of regenerating cells on day 10 (×400).

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