Preventive Effect of Rolipram, a Phosphodiesterase 4 Enzyme Inhibitor, on Oxidative Renal Injury in Acute Ascending Pyelonephritis Model in Rats

Görür, Sadık; Çeli̇k, Sefa; Hakverdı, Sibel; Aslantaş, Özkan; Erdoğan, Suat; Aydın, Muhsin; Ocak, Sabahattin; Kıper, Ahmet

doi:10.1016/j.urology.2008.04.013

Cited by 14 publications

(7 citation statements)

References 27 publications

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“… 53 In support of this notion, rolipram partially rescued the proliferation defect upon FUS knockdown ( Figure 5 ). Rolipram has been shown to boost expression of antioxidizing enzymes, 54 suppress nitric oxide levels 32 , 54 and exert a protective effect in animal models of spinal cord injury 55 and neurodegeneration. 56 , 57 , 58 Although the impact of rolipram on cellular proliferation was strongest for shFUS cells, we note a small effect on the control line that may signify a general effect of rolipram on cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

A loss of FUS/TLS function leads to impaired cellular proliferation

et al. 2014

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Fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is a multifunctional RNA/DNA-binding protein that is pathologically associated with cancer and neurodegeneration. To gain insight into the vital functions of FUS and how a loss of FUS function impacts cellular homeostasis, FUS expression was reduced in different cellular models through RNA interference. Our results show that a loss of FUS expression severely impairs cellular proliferation and leads to an increase in phosphorylated histone H3, a marker of mitotic arrest. A quantitative proteomics analysis performed on cells undergoing various degrees of FUS knockdown revealed protein expression changes for known RNA targets of FUS, consistent with a loss of FUS function with respect to RNA processing. Proteins that changed in expression as a function of FUS knockdown were associated with multiple processes, some of which influence cell proliferation including cell cycle regulation, cytoskeletal organization, oxidative stress and energy homeostasis. FUS knockdown also correlated with increased expression of the closely related protein EWS (Ewing's sarcoma). We demonstrate that the maladaptive phenotype resulting from FUS knockdown is reversible and can be rescued by re-expression of FUS or partially rescued by the small-molecule rolipram. These results provide insight into the pathways and processes that are regulated by FUS, as well as the cellular consequences for a loss of FUS function.

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Section: Discussionmentioning

confidence: 99%

A loss of FUS/TLS function leads to impaired cellular proliferation

et al. 2014

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“…E. coli cells were cultured in MH broth at 37 °C overnight until harvested. According to the method of Bennett et al [37,38,39], the cells were diluted to a final concentration of approximately 10 10 organisms/mL in 1× phosphate-buffered saline, and subsequently determined by the optical density at 600 nm.…”

Section: Methodsmentioning

confidence: 99%

Comparative Pharmacokinetics of Gallic Acid, Protocatechuic Acid, and Quercitrin in Normal and Pyelonephritis Rats after Oral Administration of a Polygonum capitatum Extract

et al. 2019

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Polygonum capitatum Buch.-Ham. ex D. Don is traditionally used by Hmong for the treatment of urinary tract infections and pyelonephritis. Information regarding the pharmacokinetic behavior of the extract in the condition of pyelonephritis is lacking. In the present study, we aimed to compare the pharmacokinetic properties of gallic acid (GA), protocatechuic acid (PCA), and quercitrin (QR)—the main bioactive constituents in the herb—in normal and pyelonephritis rats. The plasma samples were collected at various time points after administration of a single dose of Polygonum capitatum extract. The plasma level of GA, PCA, and QR at the designed time points was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and drug concentration versus time plots were constructed to estimate the pharmacokinetic parameters. The AUC(0-t), AUC(0-∞), MRT(0-t), and CL of GA, PCA, and QR in pyelonephritis rats was significantly different from those of the normal rats. The results indicated that the three constituents have higher rate of uptake and slower rate of elimination in the rats with pyelonephritis, suggesting altered rate and extent of drug metabolism.

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“…The micro-infusion technique and the length of anesthesia are two important factors in the choice of rats in the present experimental model. Rats have previously been used successfully in experimental ascending UTI [21], [22], [23] models and do express the P fimbriae Galα1-4Galβ receptor for UPEC attachment in the kidney [24]. In our previous work immediate visualization of the infection site revealed that only a few bacteria succeed in initially withstanding renal filtrate flow and colonize the tubule epithelium [19].…”

Section: Introductionmentioning

confidence: 99%

Uropathogenic Escherichia coli P and Type 1 Fimbriae Act in Synergy in a Living Host to Facilitate Renal Colonization Leading to Nephron Obstruction

et al. 2011

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The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here we used multiphoton microscopy-based live animal imaging, combined with advanced surgical procedures, to investigate the role of uropathogenic Escherichia coli (UPEC) attachment organelles P and Type 1 fimbriae in renal bacterial infection. A GFP+ expressing variant of UPEC strain CFT073 and genetically well-defined isogenic mutants were microinfused into rat glomerulus or proximal tubules. Within 2 h bacteria colonized along the flat squamous epithelium of the Bowman's capsule despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow in the proximal tubule, the P and Type 1 fimbriae appeared to act in synergy to promote colonization. P fimbriae enhanced early colonization of the tubular epithelium, while Type 1 fimbriae mediated colonization of the center of the tubule via a mechanism believed to involve inter-bacterial binding and biofilm formation. The heterogeneous bacterial community within the tubule subsequently affected renal filtration leading to total obstruction of the nephron within 8 h. Our results reveal the importance of physiological factors such as filtration in determining bacterial colonization patterns, and demonstrate that the spatial resolution of an infectious niche can be as small as the center, or periphery, of a tubule lumen. Furthermore, our data show how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis.

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Preventive Effect of Rolipram, a Phosphodiesterase 4 Enzyme Inhibitor, on Oxidative Renal Injury in Acute Ascending Pyelonephritis Model in Rats

Cited by 14 publications

References 27 publications

A loss of FUS/TLS function leads to impaired cellular proliferation

A loss of FUS/TLS function leads to impaired cellular proliferation

Comparative Pharmacokinetics of Gallic Acid, Protocatechuic Acid, and Quercitrin in Normal and Pyelonephritis Rats after Oral Administration of a Polygonum capitatum Extract

Uropathogenic Escherichia coli P and Type 1 Fimbriae Act in Synergy in a Living Host to Facilitate Renal Colonization Leading to Nephron Obstruction

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