Our results suggest that Adv-bcl-xL gene transfer significantly improves ischemia/reperfusion-induced renal dysfunction via the downregulation of renal tubular apoptosis and autophagy.

We explored whether substance P (SP) via neurokinin (NK) receptor facilitates bladder afferent signaling and reactive oxygen species (ROS) formation in bladder in association with neurogenic inflammation. We evaluated ROS activity and cystometrograms as well as pelvic nervous activity in anesthetized rat bladder with SP stimulation. Our results showed that endogenous SP via NK(1), not NK(2), receptor mediated a micturition reflex. An increase in SP by electrical stimulation of the pelvic nerve or an increase in exogenous SP by intra-arterial or intrathecal administration can facilitate myogenic and neurogenic bladder contractions. Furthermore, exaggerated SP release increased ROS in the bladder and whole blood via increased mast cell degranulation, intercellular adhesion molecule expression, and leukocyte adhesion, a primary source of ROS in the inflamed bladder. Treatment with NK(1)-receptor antagonists or ROS scavengers reduced bladder intercellular adhesion molecule expression and ROS and ameliorated the hyperactive bladder response. Our study indicates that the mechanism by which SP participates in the neurogenic bladder may be complicated by its proinflammatory activity and its ability to stimulate ROS generation.

Exacerbated oxidative stress and inflammation may induce three types of programmed cell death, autophagy, apoptosis and pyroptosis in unilateral ureteral obstruction (UUO) kidney. Sulforaphane activating NF-E2-related nuclear factor erythroid-2 (Nrf-2) signaling may ameliorate UUO-induced renal damage. UUO was induced in the left kidney of female Wistar rats. The level of renal blood flow, cortical and medullary oxygen tension and reactive oxygen species (ROS) was evaluated. Fibrosis, ED-1 (macrophage/monocyte) infiltration, oxidative stress, autophagy, apoptosis and pyroptosis were evaluated by immunohistochemistry and Western blot in UUO kidneys. Effects of sulforaphane, an Nrf-2 activator, on Nrf-2- and mitochondrial stress-related proteins and renal injury were examined. UUO decreased renal blood flow and oxygen tension and increased renal ROS, 3-nitrotyrosine stain, ED-1 infiltration and fibrosis. Enhanced renal tubular Beclin-1 expression started at 4 h UUO and further enhanced at 3d UUO, whereas increased Atg-5-Atg12 and LC3-II expression were found at 3d UUO. Increased renal Bax/Bcl-2 ratio, caspase 3 and PARP fragments, apoptosis formation associated with increased caspase 1 and IL-1β expression for pyroptosis formation were started from 3d UUO. UUO reduced nuclear Nrf-2 translocation, increased cytosolic and inhibitory Nrf-2 expression, increased cytosolic Bax translocation to mitochondrial and enhanced mitochondrial Cytochrome c release into cytosol of the UUO kidneys. Sulforaphane significantly increased nuclear Nrf-2 translocation and decreased mitochondrial Bax translocation and Cytochrome c release into cytosol resulting in decreased renal injury. In conclusion, sulforaphane via activating Nrf-2 signaling preserved mitochondrial function and suppressed UUO-induced renal oxidative stress, inflammation, fibrosis, autophagy, apoptosis and pyroptosis.

This study demonstrates that hemodialysis with ERW administration may efficiently increase the H2O2- and HOCl-dependent antioxidant defense and reduce H2O2- and HOCl-induced oxidative stress.