ABSTRACT
CONTEXT: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. OBJECTIVE: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. MATERIALS AND METHODS: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor ß (TGF-ß)/Smad pathway were conducted on renal tissues. RESULTS: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. CONCLUSION: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-ß/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Nephrolithiasis/prevention & control , Animals , Cadherins/metabolism , Calcium Oxalate/toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Kidney Calculi/prevention & control , Male , Mice , Mice, Inbred C57BL , Signal Transduction/drug effects , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
Nephrolithiasis is one of the world's major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Kidney Calculi/drug therapy , Kidney/drug effects , Metabolome/drug effects , Protective Agents/therapeutic use , Animals , Calcium Oxalate/adverse effects , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Kidney Calculi/etiology , Kidney Calculi/metabolism , Kidney Calculi/pathology , Male , Metabolomics , Mice, Inbred C57BLABSTRACT
OBJECTIVE: Renal fibrosis generally results in renal failure during the end stage of chronic renal diseases. There are many cell factors including E-cadherin, α-SMA, and TGF-ß1 influencing deposition of extracellular matrix and leading to renal fibrosis. As the most important and widely-used therapy for various diseases in China for thousands of years, traditional Chinese medicine (TCM) provides a novel treatment for renal fibrosis. For clinical application, we explore the effect of Bu-Shen-Huo-Xue formula (BSHX), a traditional Chinese herbal formula, on E-cadherin and α-SMA in rats with 5/6 nephrectomy. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 5/6 nephrectomy to induce chronic renal failure (CRF); they were divided into three groups including a CRF control group, a BSHX group, and a Cozaar group, and compared with a normal control group. After 8 weeks of therapy with the respective drug, E-cadherin, α-SMA, and TGF were detected by immunohistochemistry assays in renal tissues. RESULTS: As the immunohistochemistry assays indicated, BSHX could significantly enhance the expression of E-cadherin and depress the levels of α-SMA and TGF-ß1 expression in rats' renal tissues with 5/6 nephrectomy. CONCLUSION: BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-ß1 expression.â©.
Subject(s)
Actins/metabolism , Cadherins/metabolism , Drugs, Chinese Herbal , Fibrosis/drug therapy , Kidney Diseases/drug therapy , Transforming Growth Factor beta1/metabolism , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Nephrectomy , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: The study aimed to study the safety and efficacy of 1.25 mmol/l calcium dialysate on maintenance hemodialysis (MHD) in elderly patients who suffered from secondary hypoparathyroidism. METHODS: Eighty-two elderly patients (ages ≥65) who had been in MHD with dialysate calcium at 1.5 mmol/l over 6 months and had 2 consecutive serum intact parathyroid hormone (iPTH) measurements at level below 100 pg/ml were selected and randomized into 2 groups: treatment group (41 patients, with dialysate calcium at 1.25 mmol/l) and control group (41 patients, still with dialysate calcium at 1.5 mmol/l). Both groups were studied for the duration of 12 months. The changes of serum iPTH, calcium, phosphorus, calcium and phosphorus product and other indicators as well as related adverse reactions were recorded at the following time points: before the study and 1, 3, 6 and 12 months into the study. In addition, the intimal media thickness (IMT) of carotid artery and abdominal aorta calcification score (AACS) were measured in the 0, 6 and 12 months during the study. RESULTS: (1) In the treatment group, the levels of serum corrected calcium, phosphorus and calcium-phosphate product began to decline after 1 month and exhibited further decrease 3 months later. Serum iPTH level increased significantly after 1 month into the study and the trend continued. The above markers stabilized after month 6. Compared with pre-study markers, the changes of the above markers were significant after study (p < 0.05). (2) The average IMT and AACS were evidently decreased during the 6 and 12 months of study in the treatment group. There was statistical significance (p < 0.05) when compared with the above indexes of the pre-study and the control group. (3) In the control group, there were no significant differences in above laboratory markers over the 12-month study period. (4) There was no significant difference in the adverse events observed between the 2 groups. CONCLUSION: Safety of low calcium dialysate (dialysate calcium 1.25 mmol/l) in elderly MHD patients with iPTH <100 pg/ml is good, as well as improving carotid IMT, resistance index and AACS as indexes of vascular calcification in the small study group and warrants further investigation.
Subject(s)
Calcium/pharmacology , Dialysis Solutions/chemistry , Hypoparathyroidism/etiology , Aged , Aged, 80 and over , Calcium/blood , Carotid Arteries/pathology , Case-Control Studies , Dialysis Solutions/pharmacology , Humans , Longitudinal Studies , Parathyroid Hormone/blood , Patient Safety , Phosphorus/blood , Renal Dialysis/adverse effects , Renal Dialysis/methods , Treatment Outcome , Vascular Calcification/etiologyABSTRACT
Chronic renal failure (CRF) is a serious disease related to increasing incidence and prevalence as well as decline in quality of life. Bu-Shen-Huo-Xue formula (BSHX), one of traditional herbal formulations, has been clinically employed to treat CRF for decades, but the mechanisms involved have not been investigated. In the present study, we investigated the effects of BSHX on some closely related parameters in 5/6 nephrectomy CRF rats. Rats with CRF were divided into five groups, namely, one control group, one enalapril group, and three BSHX treatment groups (0.25, 0.5, and 1 g/kg·d). The rats subjected to sham operation were used as a normal control. After eight weeks of treatment, BSHX significantly decreased the levels of Scr and BUN, downregulated the mRNA expression levels of TGF-ß 1, CTGF, NF-κB, TNF-α, and OPN, upregulated the mRNA expression of PPARγ, and reduced in situ expression of fibronectin and laminins. Histological findings also showed significant amelioration of the damaged renal tissue. BSHX protects 5/6 nephrectomy rats against chronic renal failure probably via regulating the expression of TNF-α, NF-κB, TGF-ß 1, CTGF, PPARγ, OPN, fibronectin, and laminins and is useful for therapy of CRF.
ABSTRACT
BACKGROUND: The goal of this study was to investigate underlying factors of parathyroid dysfunction in elderly patients undergoing maintenance hemodialysis. METHODS: A total of 286 patients on maintenance hemodialysis were included. Hemoglobin, serum creatinine (Scr), blood urea nitrogen (BUN), serum calcium, serum phosphorus (P), intact parathyroid hormone (iPTH), and serum albumin (Alb) were measured and analyzed both before and after dialysis. RESULTS: A higher incidence of low iPTH level (<150 pg/l) was observed in the elderly group than that in the non-elderly group (55.8 vs. 36.7%, p < 0.05). Elderly patients had a shorter dialysis duration, lighter dry weight, lower concentrations of BUN, Scr, P, iPTH, Alb and standard protein nitrogen present rate (nPNA) compared to that of non-elderly group patients (p < 0.05). CONCLUSIONS: Low iPTH level occurs more frequently in elderly hemodialysis patients. Furthermore, age, serum P, serum Alb and nPNA were independently associated with a low iPTH level.