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

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.