Hypoxia preconditioning attenuates bladder overdistension‐induced oxidative injury by up‐regulation of Bcl‐2 in the rat

Abstract

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.

Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion

“…This method of HPC was previously established as one to which most rats can adapt successfully. 40,41 Intestinal I/R Rats exposed to normoxia (NM) and HPC were divided to three subgroups each: one group was killed directly as controls (cont), and the second and third groups underwent surgical procedures of either sham operation (sham) or intestinal I/R. After fasting overnight, rats were anesthetized by intraperitoneal injection of urethane (1.2 mg/kg body weight) and intubated in the trachea to keep the airway unimpeded.…”

Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver

“…Acute urinary retention (AUR) with a volume beyond physiological tolerance (overdistension) can become a physiological or pathological stressor, resulting in bladder injury (40). In addition, excessive stimulation of mechanical afferents in the overdistended urinary bladder could evoke a sympathetic nerve-mediated vesicovascular reflex, which could lead to vasoconstriction and functional impairment of the heart and kidney (7,23) and, likely, in other visceral organs.…”

Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA

“…Formalin-fixed, paraffin-embedded (FFPE) tissues (n = 58, ages [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] were sectioned at 5 mm, transferred onto Fisher Superfrost Plus slides, deparaffinized, rehydrated and then subjected to antigen retrieval using Vector Antigen Unmasking Solution, pH 6.0 (Vector Laboratories) for 1 h at 80°C. The sections were incubated in a humidity chamber overnight at 4°C with a mouse monoclonal antibody developed against 4HNE-modified low-density lipoprotein (clone NA59) that binds to lysine adducts of 4HNE.…”

“…[18][19][20][21][22][23][24][25][26][27] Of special relevance to carcinogenesis are adaptive responses to chronic oxidative stress identified that might lead to the evolution of subpopulations of cells that can evade mechanisms that limit the propagation of cells with oxidatively-damaged DNA, notably, increased resistance to apoptosis [28][29][30][31] and tolerance to DNA damage. [32][33][34] The chronic oxidative stress final-common-path hypothesis, referred to above, is based on the following considerations.…”