Efficiency of tazobactam/piperacillin in lethal peritonitis is enhanced after preconditioning of rats with O3/O2-pneumoperitoneum.

Insufflation of ozonized oxygen into the peritoneum (O3/O2-pneumoperitoneum [O3/O2-PP]) of rats reduced the lethality of peritonitis. We evaluated the prophylactic effect of O3/O2-PP combined with tazobactam/piperacillin (TZP) in polymicrobial lethal peritonitis. Wistar rats were conditioned by daily repeated insufflation of ozone for 5 days, and hematologic parameters were determined. Sepsis was induced by i.p. injection of cecal material derived from donor rats. Simultaneously, TZP was applied at a single dosage of 65 mg/kg or at two dosage schedules of 65 mg/kg each at an interval of 1 h. The conditioning effect of O3/O2-PP on the number of blood cells was measured before inoculation of bacteria. The mRNA levels of proinflammatory cytokine IL-lbeta and TNF-alpha were determined at 4 h post infection in spleen and liver by semiquantitative in situ hybridization analysis. Preconditioning of rats by O3/O2-PP enhanced the number of blood leukocytes and granulocytes and increased the survival rate of septic rats up to 33%. The combination of O3/O2-PP and TZP further enhanced the survival rate up to 93%. This effect was accompanied by a reduced amount of IL-1beta and TNF-alpha mRNA in spleen and liver. In contrast, in non-infected animals the combination of O3/O2-PP and TZP enhanced IL-1beta and TNF-alpha mRNA in the spleen and IL-1beta mRNA in liver when compared with TZP- and sham-treated controls. The preconditioning effect of O3/O2-PP seems to support the biological effectiveness of TZP by altering the immune status before and during the onset of sepsis. The combined therapy could be a simple, preoperative intervention for abdominal surgery to reduce postoperative morbidity and mortality.

Ozone therapy on rats submitted to subtotal nephrectomy: role of antioxidant system.

Chronic renal failure (CRF) represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy). Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg) for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks). Renal plasmatic flow (RPF), glomerular filtration rate (GFR), the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function) in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group) showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP) figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD) and catalase (CAT) showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone rectal administrations produced a delay in the advance of the disease, protecting the kidneys against vascular, hemorheological, and oxidative mechanisms. This behavior suggests ozone therapy has a protective effect on renal tissue by downregulation of the oxidative stress shown in CRF.

Effects of ozone oxidative preconditioning on TNF-alpha release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock.

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-alpha levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-alpha levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-alpha production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems.

Effects of Ozone Oxidative Preconditioning on TNF-¦Á Release and Antioxidant-Prooxidant Intracellular Balance in Mice During Endotoxic Shock

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-¦Á levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-¦Á was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-¦Á levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-¦Á levels in a dose-dependent manner. Statistically significant decreases in TNF-¦Á levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78percent), 0.4 (98 percent), and 1.2 (99 percent). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-¦Á production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems(AU)

El ozono es un oxidante preacondicionamiento profil¨¢cticos, que favorece el equilibrio prooxidant antioxidantes para la preservaci¨®n de estado redox celular por el aumento de los sistemas antioxidantes end¨®genos en tanto in vivo como in vitro modelos experimentales. Nuestro objetivo es analizar el efecto oxidante del ozono preacondicionamiento en suero los niveles de TNF-¦Á y como modulador del estr¨¦s oxidativo en el tejido hep¨¢tico en entodoxic choque modelo (ratones tratados con lipopolisac¨¢rido (LPS)). Ozono y ox¨ªgeno gaseoso mezcla que se administr¨® por v¨ªa intraperitoneal (0,2, 0,4 y 1,2 mg / kg) una vez al d¨ªa durante cinco d¨ªas antes de LPS (0,1 mg / kg, intraperitoneal). TNF-¦Á se midi¨® por la citotoxicidad de las c¨¦lulas L-929. Par¨¢metros bioqu¨ªmicos, como las materias ¨¢cido tiobarbit¨²rico (TBARS), la actividad enzim¨¢tica de la catalasa, glutation peroxidasa y glutati¨®n S-transferasa se midieron en el tejido hep¨¢tico. Una hora despu¨¦s de la inyecci¨®n de LPS hubo un aumento significativo en los niveles de TNF-¦Á en suero de rat¨®n. Ozono y ox¨ªgeno gaseoso mezcla suero reducido los niveles de TNF-¦Á en una manera dosis-dependiente. Disminuciones estad¨ªsticamente significativas en los niveles de TNF-¦Á despu¨¦s de la inyecci¨®n de LPS se observaron en ratones pretratados con ozono intraperitoneal aplicaciones en 0,2 (78por ciento), 0,4 (98 por ciento) y 1,2 (99 por ciento). Tambi¨¦n un aumento significativo en el contenido de TBARS se observ¨® en el tejido hep¨¢tico de ratones tratados con LPS, mientras que la actividad enzim¨¢tica de la glutati¨®n S-transferasa y glutati¨®n peroxidasa disminuy¨®. Sin embargo, en la capa de ozono, los animales tratados una disminuci¨®n significativa en el contenido de TBARS se apreciaba, as¨ª como un aumento en la actividad de enzimas antioxidantes. Estos resultados indican que el ozono preacondicionamiento oxidativo ejerce efectos inhibidores sobre la producci¨®n de TNF..........................

Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models. AIMS: To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity. METHODS: Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase. RESULTS: Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent. CONCLUSIONS: Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.

Inhibition of tumor necrosis factor-alpha release during endotoxic shock by ozone oxidative preconditioning in mice.

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in both in vivo and in vitro experimental models. The aim of this study was to analyze the effect of ozone oxidative preconditioning on the level of tumor necrosis factor-alpha (TNF-alpha) in the serum of mice treated with lipopolysaccaride (LPS). Pretreatment with an ozone/oxygen gaseous mixture was administered intraperitoneally (0.2, 0.4 and 1.2 mg/kg) or by rectal application (0.2 and 0.4 mg/kg) once daily during five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. One hour after LPS injection, a significant mean increase of TNF-alpha in mouse serum was observed. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed either with ozone intraperitoneal applications at 0.2 (78 %), 0.4 (98.5 %) and 1.2 (98.6 %) mg/ kg or by rectal application at 0.2 (46.2 %) and 0.4 (97.4 %) mg/kg. These results indicate that ozone oxidative preconditioning inhibits TNF-alpha production.