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1.
Phytomedicine ; 86: 153555, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33852977

ABSTRACT

BACKGROUND: Calcium oxalate (CaOx) crystal deposition and crystal-induced renal tubular epithelial cell injury have been found to fundamentally contribute to the formation of CaOx nephrolithiasis. PURPOSE: In the current work, we aim to study the role and mechanism of kaempferol in CaOx crystal kidney deposition and crystal-induced renal injury. STUDY DESIGN: Mice models and HK-2 cells were used to investigate the effect of kaempferol in CaOx crystal-induced renal injury and crystal deposition in the kidney and its underlying mechanism by a series of experiments. METHODS: CaOx crystal deposition in mice renal tubulars and tubular damage were evaluated. And crystal adhesion to HK-2 cells, as well as cellular injury were identified. Furthermore, the effect of kaempferol on the expression of androgen receptor (AR) in renal tubular epithelial cells was assessed. The interaction between AR and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and the intrinsic molecular mechanism of how AR regulated NOX2 in HK-2 cells were dissected. Additionally, several different assays were applied to analyze the expression levels of various related genes in this study. RESULTS: It was revealed that kaempferol reduced CaOx crystal deposition in renal tubulars and crystal adhesion to HK-2 cells. Meanwhile, the results of in vivo and in vitro experiments corroborated that crystal-associated cellular injury, oxidative stress, inflammation and over-expression of OPN and CD44 in the kidney were ameliorated by kaempferol. Moreover, kaempferol functioned on inhibiting the expression of AR in renal tubular epithelial cells, and AR was able to up-regulate the expression of NOX2 at the transcriptional level by directly binding to the promoter of NOX2. Kaempferol decreased crystal deposition and crystal-induced renal oxidative and inflammatory injury by the down-regulation of AR/NOX2 signaling pathway. CONCLUSION: Taken together, our study findings suggest that kaempferol has a suppressive effect on renal AR expression, which can attenuate CaOx crystal deposition and crystal-induced kidney injury through repressing oxidative stress and inflammation in the kidney by modulating the AR/NOX2 signaling pathway. It demonstrates that kaempferol may have preventive and therapeutic potential for CaOx nephrolithiasis.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Kaempferols/pharmacology , Kidney/drug effects , Nephrolithiasis/prevention & control , Signal Transduction/drug effects , Animals , Calcium Oxalate/metabolism , Mice , Oxidative Stress/drug effects
2.
Br J Pain ; 13(3): 177-184, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31308942

ABSTRACT

AIM: To explore whether the total pain experience differs after (partial) kidney tumour nephrectomies via flank, transabdominal or laparoscopic access. MATERIALS AND METHODS: We analyzed retrospectively 107 patients with flank, 12 with transabdominal and 21 with laparoscopic interventions. For pain treatment, conventional analgesics (A) or intravenous patient-controlled analgesia (PCIA) or thoracic peridural analgesia (tPDA) were used. Self-reported pain was measured with a Visual Analogue Scale three times daily. The area under the curve (AUC) at rest (R) and during a standardized body movement (M) were calculated from the intervention till the end of the second T(0-2) and seventh postoperative day T(0-7), respectively. RESULTS: The median AUC for T(0-2) at R was more intense for laparoscopy (13) than for flank incision (A, 9) and approximately the same during M. For flank incisions (A), the median AUC at R rises from 9 for T(0-2) to 22 for T(0-7) and at M the median AUC increases from 18 to 37. In contrast, laparoscopy did not cause further pain after the second postoperative day. Furthermore, with flank incision for T(0-2), at R, tPDA was superior to A (median AUC: 5 versus 9, p = 0.02) and at M again tPDA (median AUC: 12) had a better pain-control as A (18) or even as PCIA (19, p = 0.005). CONCLUSION: Laparoscopic nephrectomies cause a relatively intense mean cumulative pain for T(0-2) and a subsequent absence of pain. However, flank incisions went on to increased pain levels until the seventh postoperative day with tPDA as most effective therapy.

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