Korean J Urol.  2008 Oct;49(10):937-944. 10.4111/kju.2008.49.10.937.

Melatonin and Cranberry Attenuate Infection-induced Apoptotic Renal Damage in a Vesicoureteral Reflux Rabbit Model

• Kim SW
• Han CH

• KMID: 1204325
• DOI: http://doi.org/10.4111/kju.2008.49.10.937

Abstract

PURPOSE: We evaluated the protective effects of melatonin and cranberry on infection-induced renal damage in a rabbit model of vesicoureteral reflux(VUR).
MATERIALS AND METHODS
Thirty-six New Zealand male rabbits were divided into the following 5 groups: 1) control, 2) VUR, 3) E. coli, 4) cranberry, and 5) melatonin. After creating unilateral VUR, infection was induced by intravesical instillation of an E. coli suspension. Cranberry powder was supplied with the feed. Melatonin was injected into the peritoneal cavity. Three weeks after surgery, the rabbits were sacrificed, and the kidneys were extirpated and examined histopathologically to evaluate inflammation, fibrosis, and tubular changes. Apoptosis in the renal tissue was assessed with a terminal deoxynucleotidyl transferase(TdT)-mediated deoxyuridine triphosphate(dUTP) in situ nick-end labeling(TUNEL) study.
RESULTS
Grossly, the refluxing kidney was larger than the contralateral normal kidney, and the refluxing ureter was dilated and tortuous. Microscopic examination of the kidneys from the E. coli group showed an apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from the reflux, cranberry, and melatonin groups showed mild mononuclear cell infiltration without interstitial fibrosis. The mean number of apoptotic cells in the kidneys of the E. coli group was significantly higher than that in the control, cranberry, and melatonin groups(p<0.05), but there was no significant difference between the cranberry and the melatonin groups.
CONCLUSIONS
This study demonstrates that the balance of apoptotic activity may play a key role in the development of reflux nephropathy. Melatonin and cranberry may prevent infection-induced renal damage by attenuating apoptosis.

Keyword

Vesico-ureteral reflux; Apoptosis; Cranberry; Melatonin

MeSH Terms

Male
Humans
Rabbits
Animals

Figure

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  Fig. 1. Histologic findings from the kidneys obtained 3 weeks after surgery. There was no histologic change and inflammation in the control group (A); there was a mild mononuclear cell infiltration in the vesicoureteral reflux (VUR) group (B), mild-to-moderate mononuclear cell infiltrations in the cranberry (C) and melatonin (D) groups, but a marked periglomerular mononuclear cell infiltration and tubular dilatation with atrophy and interstitial fibrosis in the E. coli group (E, F) (H&E, x200).

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  Fig. 2. The terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) in situ nick-end labeling (TUNEL) study in the rabbits' kidneys. Kidneys from the control and VUR groups showed few apoptotic cells (A, B). There was a marked increase in apoptotic cells in the E. coli group (E, F). Apoptotic cells are frequently found in the cranberry (C), and melatonin (D) groups. Arrows indicate apoptotic cells (x400).

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  Fig. 3. Mean number of apoptotic cells in each group. (A) Mean number of apoptotic cells of the E. coli group is higher than the control and VUR groups. (B) Mean number of apoptotic cells of the cranberry group and the melatonin group is lower than the E. coli group. VUR: vesicoureteral reflux; ∗: p＜0.05 compared with the other group.

Reference

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