Ozonated autohemotherapy: protection of kidneys from ischemia in rats subjected to unilateral nephrectomy.

BACKGROUND: Ozonated autohemotherapy (OA) has been previously successfully used in the treatment of patients affected by peripheral occlusive arterial disease. OA consists of an intrafemoral reinfusion of autologous blood previously exposed to a mixture of oxygen/ozone (O2/O3). This study analyzes the effects of OA in protecting rat kidney from ischemia and ischemia/reperfusion damage. METHODS: We performed OA 30 min before the induction of 60 min renal ischemia or at the induction of 60 min postischemic reperfusion in rats subjected to unilateral nephrectomy. In addition, to evidence the possible protection induced by O2/O3 on endothelial functions, the present study analyzes the in vitro effects of O2/O3 on oxygen consumption by human umbilical vein endothelial cells (HUVEC). RESULTS: 1) OA preserves rat kidney functions and architecture, as demonstrated by the improved levels of serum creatinine and blood urea nitrogen and by histology; 2) such protection does not correlate with the increase of plasmatic nitric oxide, but is compatible with a focal renal increase of renal ßNADPH-diaphorase; 3) treatment of HUVEC with O2/O3 significantly increases both the rate of oxygen consumption and the mitochondrial activity assessed by confocal microscopy. CONCLUSION: The preservation of the mitochondrial activity of endothelium could in vivo limit the endothelial dysfunction provoked by the Isc or Isc/R processes.

Protective effect of EDTA preadministration on renal ischemia.

BACKGROUND: Chelation therapy with sodium edetate (EDTA) improved renal function and slowed the progression of renal insufficiency in patients subjected to lead intoxication. This study was performed to identify the underlying mechanism of the ability of EDTA treatment to protect kidneys from damage. METHODS: The effects of EDTA administration were studied in a rat model of acute renal failure induced by 60 minutes ischemia followed or not by 60 minutes reperfusion. Renal ischemic damage was evaluated by histological studies and by functional studies, namely serum creatinine and blood urea nitrogen levels. Treatment with EDTA was performed 30 minutes before the induction of ischemia. Polymorphonuclear cell (PMN) adhesion capability, plasmatic nitric oxide (NO) levels and endothelial NO synthase (eNOS) renal expression were studied as well as the EDTA protection from the TNFalpha-induced vascular leakage in the kidneys. Data was compared by two-way analysis of variance followed by a post hoc test. RESULTS: EDTA administration resulted in the preservation of both functional and histological parameters of rat kidneys. PMN obtained from peripheral blood of EDTA-treated ischemized rats, displayed a significant reduction in the expression of the adhesion molecule Mac-1 with respect to controls. NO was significantly increased by EDTA administration and eNOS expression was higher and more diffuse in kidneys of rats treated with EDTA than in the controls. Finally, EDTA administration was able to prevent in vivo the TNFalpha-induced vascular leakage in the kidneys. CONCLUSION: This data provides evidence that EDTA treatment is able to protect rat kidneys from ischemic damage possibly through the stimulation of NO production.