The relevance of immune responses to partial bladder outlet obstruction and reversal.

AIMS: Partial bladder outlet obstruction (PBOO) causes tissue inflammation, a significant increase in markers of systemic oxidative stress, and proliferation of circulating myeloid-derived suppressor cells. Here, we investigated the regulatory mechanisms underlying inflammation and helper T cell involvement in PBOO. METHODS: Surgical PBOO was performed in four groups of rats: control (C), obstruction at 2 (O2) and 4 (O4) weeks, and 4 weeks after the relief of PBOO (R4) (n = 6 each). The urinary levels of prostaglandin E metabolite (PGEM), expression of inflammatory cytokines (IL-6 and IL-17) in the bladder, numbers of peripheral blood regulatory T cells (Treg cells), and levels of TGF-ß1 were assessed via immunohistochemistry, flow cytometry, or ELISA. RESULTS: The levels of urinary PGEM, bladder IL-17, and TGF-ß1 and the numbers of peripheral Treg cells (Foxp3) were all significantly increased at 2 and 4 weeks after PBOO. PGEM, IL-17, and Treg cells (Foxp3) were decreased after the relief of PBOO, while the levels of TGF-ß1 continued to increase. CONCLUSIONS: Transient PBOO triggers an acute, reversible increase in inflammatory cytokines and Treg cells. The distinct dynamics of individual inflammatory markers support their potential use as markers for monitoring bladder inflammation.

Transient increase in circulating myeloid-derived suppressor cells after partial bladder outlet obstruction.

PURPOSE: Partial bladder outlet obstruction causes a significant increase in tissue and systemic oxidative stress markers and tissue inflammatory cytokine levels. Myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone are believed to be associated with oxidative stress and inflammation. We investigated alterations in plasma myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone levels in partial bladder outlet obstruction and after its reversal. MATERIALS AND METHODS: Rats with surgically induced partial bladder outlet obstruction were divided into 4 groups of 3 each, including sham treated, 4-week obstruction, and 4 and 8-week obstruction with relief. Plasma levels of circulating myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone were assessed by flow cytometry or enzyme-linked immunosorbent assay. RESULTS: The circulating myeloid-derived suppressor cell level was markedly increased in the obstruction group compared to the sham treated group and it returned to normal in the 4 and 8-week obstruction with relief groups. Plasma IFN-γ, IL-10 and aldosterone were similarly increased in the obstruction group and returned to normal in the 4 and 8-week obstruction with relief groups. CONCLUSIONS: Levels of circulating myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone were increased in rats with partial bladder outlet obstruction but returned to normal after reversal. This suggests that an increase in these parameters may be a good predictive indicator of patients at increased risk for urinary symptoms.

Reversing bladder outlet obstruction attenuates systemic and tissue oxidative stress.

UNLABELLED: What's known on the subject? and What does the study add? Oxidative damage in bladder tissue and systemic oxidative biomarkers were both found to be increased in rabbits with partial bladder outlet obstruction. It is shown that the reversal of partial bladder outlet obstruction will attenuate the systemic oxidative stress. OBJECTIVE: To investigate whether partial bladder outlet obstruction (PBOO) increases systemic oxidative stress and whether relief of PBOO could attenuate this stress. MATERIALS AND METHODS: Surgically created PBOO in male New Zealand white rabbits was assessed after 4 weeks in one group of rabbits (n = 4), and was relieved in two additional groups of rabbits (n = 4 each) that were assessed at 4 and 8 weeks after relief of PBOO. Four sham-operated rabbits served as controls. The assessed oxidative stress biomarkers included urinary and plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA), total anti-oxidant capacity (TAC) and glutathione (GSH). In addition, the copy number of mitochondrial DNA and the 8-OHdG content in bladder tissues from these rabbits were also determined at the beginning and at indicated time points in the experiments. RESULTS: There were significant increases in both the 8-OHdG levels of urine, plasma and bladder tissue and the plasma MDA after induction of PBOO. There were also significant decreases in the TAC, in GSH levels and in mitochondrial DNA copy number in bladder tissues after PBOO. Most importantly, all of the values returned toward the control levels after the PBOO was reversed at 8 weeks. CONCLUSION: PBOO increases systemic and oxidative stress and its reversal results in a progressive reduction of both systemic and tissue oxidative stress.

Oxidative stress biomarkers in urine and plasma of rabbits with partial bladder outlet obstruction.

UNLABELLED: What's known on the subject? and What does the study add? It has been known that there is an increase of oxidative damage in the bladder tissues of animals after PBOO. However, no reliable oxidative stress biomarkers in either urine or plasma have been available for the assessment of the severity of PBOO. This study clearly demonstrated that the levels of oxidative stress biomarkers are increased in urine and plasma of the rabbits with PBOO. OBJECTIVE: To investigate oxidative stress and oxidative damage biomarkers in urine and plasma after partial bladder outlet obstruction (PBOO) in rabbits. MATERIALS AND METHODS: In all, 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO-treated groups for 2, 4 and 8 weeks. The oxidative stress biomarkers assessed included urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA). We also measured the total antioxidant capacity (TAC) in blood plasma. 8-OHdG, MDA and TAC were measured at both the beginning and indicated time points of the experimental design. RESULTS: There was no significant difference in body weight among rabbits in the four groups. However, there was a significant increase in bladder weight after 2 weeks of PBOO. After 4 and 8 weeks of PBOO, there was an additional significant increase in bladder weight in all three groups. There was no difference in blood creatinine levels among the groups. In the 4- and 8-week PBOO groups, there was a significant increase of 8-OHdG in urine and of MDA in plasma, while there was a significant decrease in TAC in plasma. CONCLUSION: The results showed that oxidative stress could be detected in the plasma and urine of rabbits after 4 and 8 weeks of PBOO, and not only from bladder tissue as previously reported. Thus, there could be an easy and alternative way to evaluate bladder function by analysis of urine and/or plasma. Additionally, rabbits with chronic PBOO showed an increase in systemic oxidative stress, which could be a novel starting point for examining the link between the lower urinary tract symptoms/benign prostate hyperplasia and metabolic syndrome in future studies.

Advanced glycation end products enhance amyloid precursor protein expression by inducing reactive oxygen species.

Accumulation of senile plaques comprising Abeta and neurofibrillary tangles is a major hallmark in the brain of AD patients. Ample evidence has shown that inflammation and reactive oxygen species (ROS) increase in the AD patient's brain. However, the pathogenesis of AD is unclear. Some risk factors of AD include age, sex, genetics, and chronic disease. Epidemiological studies have suggested that the levels of advanced glycation end products (AGEs) are enhanced in patients with diabetes mellitus and during the aging process. At the same time, evidence indicates a moderately increased risk of development of AD in diabetic patients. AGEs may play a role in the pathogenesis of AD. In this study, we proposed that amyloid precursor protein (APP) expression was regulated by AGEs. Our data showed that APP was up-regulated by AGEs in vitro and in vivo, and pretreatment of cells with an ROS inhibitor (N-acetyl-L-cysteine) blocked the effects of AGEs. In conditioned medium, the level of Abeta(1-42) increased after AGE treatment. Furthermore, the combination of AGEs and aggregated Abeta(1-42) increased ROS production and decreased cell viability. We suggest that AGEs participate in AD development and are an important risk factor in the pathogenesis of AD.