Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1β and TNF-α is suggested to contribute to the observed changes in kidney gene expression.
Abbreviations & Acronyms 8-OHdG = 8-hydroxy-2 0deoxyguanosine Alox15b = arachidonate 15lipoxygenase AP = activity product BP = blood pressure BUN = blood urea nitrogen CaOx = calcium oxalate Cldn10 = claudin 10 Cp = ceruloplasmin Cr = creatinine DSs = Dahl salt-sensitive EA = ethylene glycol + alfacalcidol EG = ethylene glycol EPL = eplerenone HE = HS + EA HEE = HS + EA + EPL HR = heart rate HS = high salt IPA = ingenuity pathway analysis LOX = lipoxygenase MAPK = mitogen-activated protein kinase MMP7 = matrix metallopeptidase-7 MR = mineralocorticoid receptor NADPH = nicotinamide adenine dinucleotide phosphate RAS = renin-angiotensinaldosterone system ROS = reactive oxygen species TGF = transforming growth factor Umod = uromodulin Correspondence: KatsuhitoObjectives: To study the promotive effect of salt-induced hypertension on crystal deposition and urolithiasis using a salt-sensitive rat hypertension model. Methods: Hyperoxaluria and hypercalciuria were induced in male Dahl salt-sensitive rats with administration of ethylene glycol and alfacalcidol. Hypertension was induced by a high-salt diet. Eplerenone, a selective mineralocorticoid receptor antagonist, was given. Blood and urine were collected to evaluate renal function, electrolytes and the blood renin-angiotensin-aldosterone system. Renal calcium content was also evaluated. Histological examination, transcriptome analysis with DNA microarray and semiquantitative reverse transcriptase polymerase chain reaction were carried out. Results: A high-salt diet increased crystal deposition in Dahl salt-sensitive rats with hypertension, and eplerenone administration significantly suppressed it. The mRNA expression profile was associated with crystal formation, growth, adhesion and cellular injury, and it was regulated in the group exposed to a high-salt diet and ethylene glycol. Conclusions: A high-salt diet has a promotive effect on salt-sensitive hypertension and urolithiasis. This promotive effect can be prevented by eplerenone administration. Hence, salt-sensitive hypertension has promotive effects on crystal deposition in Dahl salt-sensitive rats.
(Objective) Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. (Results) Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. (Conclusion) This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer.
Objectives To examine the effects of the selective xanthine oxidase inhibitor febuxostat on the expression of inflammation‐related genes involved in stone formation. Methods Madin‐Darby canine kidney cells were exposed to febuxostat, followed by calcium oxalate monohydrate crystals. Monocyte chemoattractant protein‐1 messenger ribonucleic acid expression levels were determined by real‐time reverse transcription polymerase chain reaction analysis. Deoxyribonucleic acid microarray analysis was utilized to evaluate gene expression. Results Calcium oxalate monohydrate crystals activated monocyte chemoattractant protein‐1 messenger ribonucleic acid expression in a time‐ and concentration‐dependent manner. Febuxostat suppressed monocyte chemoattractant protein‐1 expression. The expression levels of a group of inflammatory genes, including interleukin‐8 and chemokine (C‐X‐C motif) ligand 10, which are downstream of reactive oxygen species, fluctuated similarly to the observed monocyte chemoattractant protein‐1 fluctuations and were reduced by febuxostat pretreatment. Conclusions Febuxostat exerts preventive effects against reactive oxygen species production and oxidative stress, and might represent a potential treatment for calcium oxalate stones. In the present study, febuxostat downregulated the calcium oxalate monohydrate crystal‐induced monocyte chemoattractant protein‐1 messenger ribonucleic acid expression.
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