• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.661-670
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• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• 한국임상수의학회지
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• 제28권1호
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• 한방재활의학과학회지
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• 제21권1호
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• pp.1-22
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• 2011

Objectives : This study was undertaken to verify the effects of Wolbigachul-tang1(WBCEx1) on obesity using high fat diet-induced male mice and to investigate the molecular mechanisms involved. Methods : 8-week old C57BL/6 mice were divided into 5 groups; lean control, obese control, WBCEx1, 2, 3. After mice were treated with WBCEx1(water extract), 2(30% ethanol extract), 3(water extract; Ephedra sinica Stapf., Gypsum fibrosum) for 12 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism, the messenger RNA(mRNA) expression of peroxisome proliferator activated receptor(PPAR)$\alpha$ target genes were measured. In addition, $PPAR{\alpha}$ target gene expression was examined in liver, white adipose tissue and skeletal muscle. Results : 1. WBCEx1-treated mice had significantly lower body weight gain and feeding efficiency ratio. 2. Consistent with the effects on body weight gain, WBCEx1 decreased the weights of epididymal and retroperitoneal white adipose tissue, inguinal subcutaneous adipose tissue, and brown adipose tissue. 3. WBCEx1 significantly decreased plasma triglyceride and total cholesterol levels. 4. The size of adipocytes were significantly decreased by WBCEx1, whereas the adipocyte number per unit area was increased. Hepatic lipid accumulation was decreased by WBCEx1. 5. WBCEx1 did not affect the mRNA expression of $PPAR{\alpha}$ target genes in liver, adipose tissue, and skeletal muscle. 6. Plasma asparate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatine concentrations were in the physiological range. Liver and kidney weights were significantly lower following WBCEx treatment compared with obese controls, indicating that WBCEx does not show any toxic effects on liver and kidney. Conclusions : These results suggest that WBCEx1-induced body weight reduction is associated with appetite control and mediated by a mechanism other than the activation of $PPAR{\alpha}$.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.547-561
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• 2024

In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of Ruminococcus gnavus (R. gnavus) on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of R. gnavus for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of R. gnavus effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, R. gnavus administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered R. gnavus up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and R. gnavus may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.