The possible mechanism that causes free radical elevation in the kidney may be different in the course of nephrolithiasis after ethylene glycol treatment. Initially the systemic circulation may bring the toxic substance into the kidney and cause it to produce free radicals. In the late stage gradually infiltrating leukocytes and decreased antioxidant enzyme activities may cause the kidney to remain under excessive oxidative stress.

Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis-and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis-and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusionenhanced mitochondrial apoptosis-and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

Abstract. Renal sensory responses and reflex function were examined in rats 24 h after 45 min of ischemic injury caused by unilateral renal arterial occlusion (RAO). The integrity of renal pelvic mechanoreceptor (MRu)-mediated renorenal reflex was examined. An increase in ipsilateral afferent renal nerve activity (ARNA) and a reflex decrease in efferent renal nerve activity (ERNA) and contralateral diuresis and natriuresis produced by increasing the intrapelvic pressure were seen in sham-operated (Sham) rats, but it was largely attenuated in RAO rats. Using single-fiber recordings of the renal MRu discharge, graded increases in intrapelvic pressure or renal pelvic administration of substance P (SP) resulted in pressureor concentration-dependent increases in ARNA in the control kidney of Sham rats, whereas attenuated responses were seen in the postischemic kidney of RAO rats. The unresponsiveness of renal MRus in RAO rats was accompanied by an insufficient release of SP. However, the baseline SP release is higher in RAO kidneys due to a reduced neutral endopeptidase (NEP) activity in the renal pelvis of the postischemic kidney. No changes in NK-1 receptor mRNA levels were demonstrated; however, the expression of NK-1 receptors in the plasma membrane of RAO pelvis were decreased, possibly resulting from the internalization of the receptors associated with ␤-arrestin trafficking. Renal excretory responses after saline loading were significantly lower in the postischemic kidney of RAO rats than in Sham rats. Responses of ARNA and ERNA were also lower. It is concluded that the defective activation of renal sensory mechanoreceptors in the postischemic kidney results from an inadequate release of SP after mechanostimulation and the reduced functional NK-1 receptors.Ischemia-induced acute renal failure is characterized by renal hypoperfusion, decreased renal function, and nitrogen waste retention (1). Complete renal artery occlusion has been used in animal models to determine the mechanisms involved in the pathogenesis of acute renal failure (2). Previous studies of rats after 45 min of unilateral renal arterial occlusion (RAO) and 24 h of reperfusion have demonstrated renal hypofunction in the postischemic kidney (3,4) and abnormal renal nerve activity (5). Certain experimental approaches, such as infusion of atrial natriuretic peptide (ANP) (6) or saline (5,7), can restore renal function after renal ischemia, but recovery of urinary excretion is never complete. Surgical and pharmacologic renal denervation improves renal excretion in response to natriuretic stimuli and prevents the development of acute renal failure (8). These findings suggest that the defective natriuretic response seen in ischemic acute renal failure is frequently associated with increased renal sympathetic nerve activity; however, the underlying mechanism affecting renal nerve activity in this condition, especially the role of afferent renal nerve activity, is not known.We have demonstrated an impaired renal sensory response in rat models associated...

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We explored whether hypoxic preconditioning minimizes oxidative injury induced by overdistension/emptying in the rat bladder. For hypoxic preconditioning, female Wistar rats were placed in a hypobaric chamber (380 Torr) 15 h day −1 for 28 days. Overdistension was induced by infusion of two times the threshold volume of saline into the bladder and was maintained for 1 or 2 h, followed by drainage/emptying. During overdistension (ischaemia) and emptying (reperfusion) periods, a bursting increase of reactive oxygen species (ROS) from the bladder was originated from the large numbers of infiltrating leucocytes and scattered resident cells, including urothelial, submucosal, and smooth muscle cells. ROS impaired the voiding function by a reduction of bladder afferent and efferent nerve activity and bethanecol-or ATP-induced detrusor contraction. ROS enhanced pro-apoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, and poly(ADP-ribose) polymerase (PARP) fragments with subsequent apoptotic cell formation in the insulted bladders. Hypoxia preconditioning up-regulated Bcl-2 expression in the bladder and significantly reduced the levels of ROS and apoptosis detected in the overdistension/emptying bladders and preserved partial voiding function. Bcl-2 up-regulation by hypoxia preconditioning contributes protection against overdistension/emptying-induced oxidative stress and injury in the bladder.

Excessive production of nitric oxide (NO) may play a detrimental role in the process of hypoxia-related neuropathology. This study explored whether treatment with melatonin would attenuate the neuropathological changes in the vagal ganglia following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment, young adult rats were pre-treated with melatonin at 5. 25 or 100 mg/kg injected intraperitoneally. Hypoxia was achieved by subjecting the rats to a barometric pressure of 0.2 atm (PO2 = 43 Torr) for 4 hr in an altitude chamber. Nicotinamine adenine dinucleotide phosphatediaphorase (NADPH-d) histochemistry combined with the neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to detect the NADPH-d/nNOS reactivity in the nodose ganglion (NG) at various time points following the hypoxic exposure. In normal untreated rats, about 43% of the neurons in the NG displayed NADPH-d/nNOS reactivity. Following hypoxic exposure, both the percentage and the staining intensity of NADPH-d/nNOS positive neurons in the NG were markedly increased, but these were reduced in longer surviving animals. Quantitative analysis of cell counts revealed that about 17% of the neurons died at 14 days after hypoxia treatment. However, in hypoxic rats given different doses of melatonin pretreatment, neuronal death as well as the frequency and staining intensity of NADPH-d/nNOS reactivity of the nodose neurons were significantly decreased. The effect of melatonin on neuronal survival and NADPH-d/ nNOS expression was dose-dependent. It is therefore suggested that melatonin exerts a neuroprotective effect and may serve as a potential therapeutic strategy for prevention and/or reducing the susceptibility of nodose neurons to NO-mediated hypoxic neuropathy.

Chronic hypoxic (CH) preconditioning reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH preconditioning might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg −1 ) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day −1 ) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1β protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 ± 17, 128 ± 35 and 48 ± 21, respectively) in renal cortex, and depressed renal cortex XO (44 ± 16%) and renal cortex (20 ± 9%) and medulla (28 ± 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1β production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release.

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