OBJECTIVETo observe the effect of Cordyceps sinensis (CS) powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats, and to primarily explore its possible mechanisms.

METHODSTotally 30 male Sprague-Dawley rats were divided into the sham-operation group, the model group, and the treatment group by random digit table, 10 in each group. A chronic kidney disease (CKD) rat model was prepared by one step 5/6 nephrectomy. Rats in the treatment group were intragastrically administered with CS powder solution at the daily dose of 2 g/kg, once per day. Equal volume of double distilled water was intragastrically administered to rats in the sham-operation group and the model group. All medication lasted for 12 weeks. The general condition of rats, their body weight, blood pressure, 24 h proteinuria, urinary N-acetyl-β-D-glucosaminidase (NAG), serum creatinine (SCr) , and blood urea nitrogen (BUN) were assessed before surgery, at week 2, 4, 6, 8, 10, and 10 after surgery. Pathological changes of renal tissues were observed under light microscope. Morphological changes of mitochondria in renal tubular epithelial cells were observed under transmission electron microscope. Activities of antioxidant enzymes including reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), and malondialdehyde (MDA) in fresh renal tissue homogenate were detected. Mitochondria of renal tissues were extracted to detect levels of mitochondrial membrane potential and changes of reactive oxygen species (ROS). And expressions of cytochrome-C (Cyto-C) and prohibitin in both mitochondria and cytoplasm of the renal cortex were also measured by Western blot.

RESULTS(1) Compared with the sham-operation group, body weight was significantly decreased at week 2 (P <0. 01), but blood pressure increased at week 4 (P <0. 05) in the model group. Compared with the model group, body weight was significantly increased at week 12 (P <0. 01), but blood pressure decreased at week 8 (P < 0. 01) in the treatment group. (2) Compared with the sham-operation group, 24 h proteinuria, urinary NAG, blood SCr and BUN significantly increased in the model group (all P <0. 01). Compared with the model group, blood and urinary biochemical indices all significantly decreased in the treatment group (all P <0. 01). (3) Results of pathological renal scoring: Glomerular sclerosis index, scoring for tubulointerstitial fibrosis, degree of tubulointerstitial inflammatory infiltration were all obviously higher in the model group than in the sham-operation group (all P <0. 01). All the aforesaid indices were more obviously improved in the treatment group than in the model group (all P <0. 01). (4) Compared with the sham-operation group, activities of MnSOD and GSH-Px were significantly reduced, but MDA contents obviously increased in the renal cortex of the model group (all P <0. 01). Compared with the model group, activities of MnSOD and GSH-Px obviously increased (P <0. 05, P <0. 01), but MDA contents obviously decreased in the renal cortex of the treatment group (P <0. 01). (5) Compared with the sham-operation group, the mitochondrial membrane potential significantly decreased, but ROS levels significantly increased in the model group (all P <0.01). Compared with the model group, mitochondrial transmembrane potential increased in the treatment group, thereby inhibiting the tendency of increased production of ROS (both P < 0. 01). (6) Results of Western blot showed that, compared with the sham-operation group, expression levels of mitochondrial Cyto-C and Prohibitin were significantly reduced in the renal cortex (P <0. 01), but significantly elevated in the cytoplasm of the model group (P <0. 01). Compared with the model group, each index was obviously improved in the treatment group with statistical difference (P <0. 05, P <0. 01).

CONCLUSIONCS powder had renal protection, and its mechanism might partially depend on in- hibition of oxidative stress and protection for mitochondria.

Acetylglucosaminidase ; metabolism ; Animals ; Blood Urea Nitrogen ; Cordyceps ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; Kidney Cortex ; Kidney Diseases ; Kidney Function Tests ; Male ; Malondialdehyde ; metabolism ; Mitochondria ; Nephrectomy ; Oxidative Stress ; drug effects ; Proteinuria ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

This study is to evaluate the anti-diabetic effects of the alpha-glucosidase inhibitor valibose in a streptozotocin (STZ)-induced type 1 diabetes rat model. Diabetes was induced by a single dose of STZ (58 mg x kg(-1), ip) in SD rats, rats with elevated fasting blood glucose levels (250-450 mg x dL(-1)) were selected and divided into five groups (n = 10 in each). Another ten normal SD rats were chosen as normal group. Valibose mixed with the high sucrose diets (0.4, 1.0 and 2.5 mg 100 g(-1) diets) or acarbose (30 mg x 100 g(-1) diets) was administrated in the diabetic rats for about 5 weeks. In all groups, fasting and postprandial plasma glucose, plasma lipids, glycosylated serum protein, N-acetyl-beta-D-glucosaminidase (NAG), creatinine (Cre), blood urea nitrogen (BUN) and urine sugar levels were determined during the treatment. At the end of the experiment, the morphological alterations in kidney were evaluated by hematoxylin-eosin (HE) staining. After 3-weeks administration, valibose significantly decreased postprandial and fasting blood glucose, urine glucose, and reduced the levels of serum fructosamine. Valibose also decreased plasma triglyceride and cholesterol levels after 4 weeks treatment. These results indicated that valibose ameliorated metabolic disturbance of glucose and lipids in STZ-induced diabetic rats. In addition, valibose markedly reduced level of serum NAG and BUN, and decreased the weight index of kidney. HE staining showed reduced kidney pathological changes after valibose treatment. The findings of the present study indicate that valibose may be a novel alpha-glucosidase inhibitor for the prevention from hyperglycemia in STZ-induced type 1 diabetes rats. And valibose might have a potential role for protecting against diabetic nephropathy during hyperglycemia.
Acetylglucosaminidase ; blood ; Animals ; Blood Glucose ; metabolism ; Blood Urea Nitrogen ; Cholesterol ; blood ; Creatinine ; blood ; Cyclohexanols ; pharmacology ; Diabetes Mellitus, Experimental ; blood ; pathology ; Diabetic Nephropathies ; prevention & control ; Enzyme Inhibitors ; pharmacology ; Fructosamine ; blood ; Glycoside Hydrolase Inhibitors ; Hyperglycemia ; prevention & control ; Hypoglycemic Agents ; pharmacology ; Kidney ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood ; Weight Gain ; drug effects

Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disorder (LSD) caused by abnormalities of the enzyme alpha-N-acetylglucosaminidase (NAGLU) that is required for degradation of heparan sulfate. The patient in this study was a 4-yr-old boy. He presented with normal height and weight, pectus carinatum, and multiple persistent Mongolian spots on his back. He had mild dysmorphic features with prominent speech developmental delays and, to a lesser extent, motor developmental delays. The cetylpyridinium chloride precipitation test revealed excessive mucopolysacchariduria (657.2 mg glycosaminoglycan/g creatinine; reference range, <175 mg glycosaminoglycan/g creatinine). Thin layer chromatography showed urinary heparan sulfate excretion. NAGLU enzyme activity was significantly decreased in leukocytes (not detected; reference range, 0.9-1.51 nmol/hr/mg protein) as well as in plasma (0.14 nmol/hr/mg protein; reference range, 22.3-60.9 nmol/hr/mg protein). PCR and direct sequencing analysis of the NAGLU gene showed that the patient was a compound heterozygote for 2 mutations: c.200T>C (p.L67P) and c.1444C>T (p.R482W). The c.200T>C mutation was a novel finding. This is the first report of a Korean patient with MPS IIIB who was confirmed by molecular genetic analyses and biochemical investigation.
Acetylglucosaminidase/blood/*genetics ; Alleles ; Asian Continental Ancestry Group/*genetics ; Child, Preschool ; Chromatography, Thin Layer ; Heterozygote ; Humans ; Leukocytes/metabolism ; Male ; Mucopolysaccharidosis III/diagnosis/*genetics ; Mutation ; Polymerase Chain Reaction ; Republic of Korea ; Sequence Analysis, DNA

OBJECTIVETo study the effects of Zhuhong ointment on accumulation in the body of mercury and the pathological morphology changes of kidney, via the measurement of related indicators of the skin-impaired model rat.

METHODEighty-eight SD rats were randomly divided into the impairment control group, and high-, middle-, low-dose Zhuhong ointment groups. Each group was treated by corresponding methods for 4 weeks, and recovering for 4 weeks. Urinary potein (PRO), pH, Beta N-acetyl aminoglycosidase enzymes (NAG) and beta2-microglobulin (beta2-MG) contents in urine were taken as monitoring indexes, blood urea nitrogen (BUN) and serum creatinine (SCr) in blood and the levels of mercury in urine, blood and kidney were tested, and the pathological morphology changes of kidney were observed.

RESULTAfter treatment for 4 weeks, compared with impairment control group, the levels of mercury in urine, blood and kidney in every dose group increased significantly (P < 0.01). And the relation exists between toxicity and dose on Zhuhong ointment. After recovery for 4 weeks, the levels of mercury in urine and blood in every dose group restore normal, while the level of mercury in kidney in high- dose group still increased (P < 0.01). The level of NAG increased only in high-dose group. There was no significant difference in NAG contents between Zhuhong ointment groups and the impairment control group (P < 0.05).

CONCLUSIONExcess using Zhuhong ointment repeatedly may lead to accumulation of mercury and pathological morphology changes of kidney. So the levels of mercury in the body and related indicators of renal functions should be tested in clinical when long-term using Zhuhong ointment.

Acetylglucosaminidase ; drug effects ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Female ; Hydrogen-Ion Concentration ; drug effects ; Kidney ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Ointments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; drug effects ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVETo observe the effect of long-term external use of Goupi Gao on renal function and lead accumulation in rats.

METHODRats were externally administered with Goupi Gao at different doses (7, 3.5 and 1.75 g x kg(-1)) for 90 d. At 45 days and 90 days after administration, the renal indicator, levels of blood urea nitrogen (BU) and creatinine (Cr) in serum, beta2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) in urine were determined. Lead content in kidneys was detected by atomic absorption spectrometry.

RESULTA 90-day administration with Goupi Gao significantly enhanced the renal indicator, levels of NAG in urine and lead content in renal, when compared with the normal rats. However, the levels of BUN and beta2-MG as well as renal pathology in Goupi Gao treated rats were not obviously changed.

CONCLUSIONConsecutive administration of Goupi Gao for 90 days can increase the renal indicator and levels of NAG in urine, enhance the accumulation of lead in renal, but with no effect on excretory function of kidneys and organic changes.

Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; analysis ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Atomic ; beta 2-Microglobulin ; urine

OBJECTIVETo compare the sensitivity of early renal injury induced by mercury-containing medicine in rats, including urinary N-acetyl-beta-D-glucosdminidase (NAG), beta2-microglobulin (beta2-MG), retinol binding protein (RBP) and clusterin (CLU).

METHODBadu Shengji San(BDSJS), a mercury-containing preparation of traditional Chinese medicine, was adopted as the mercury contact drug. The lowest effective toxic dose was used to observe its effect on serum creatinine (SCr), blood urea nitrogen (BUN), and such early renal injury indicators as NAG, RBP, beta2-MG and CLU and compare the sensitivity of tested indicators.

RESULTCompared to the broken skin group, groups with administration of 60 and 120 mg x kg(-1) doses of BDSJS showed no obvious difference in SCr and BUN when kidney indicators is remarkably increased and obvious pathological changes were found in kidney tubules but with significant increase in the urinary level of CLU and the levels of NAG and RBP. H&E staining of renal tubule showed that exposure of 30 mg x kg(-1) BDSJS had no significant morphological changes, but at the same concentrations, the level of RBP was markedly increased. Urinary beta2-MG levels were markedly decreased in BDSJS 30, 60 mg x kg(-1) group rats, whereas 120 mg x kg(-1) dose group showed no obvious change in urinary beta2-MG levels.

CONCLUSIONUrinary RBP, NAG and CLU were more sensitive than SCr and BUN as indicators for early renal injury in the order of RBP > NAG > CLU, and urinary RBP, NAG would increase earlier than beta2-MG.

Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Clusterin ; urine ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVETo study the mercury accumulation in injured skin rats induced by Badu Shengji San (BDSJS), a traditional Chinese medicine preparation for external use.

METHODInjured skin rats were treated with BDSJS for consecutively 4 weeks. During the 4 weeks and the following 4 weeks after the drug withdrawal, samples were collected for determining mercury contents in blood, urine and kidney, with urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta2-microglobulin (beta2-MG) as indicators of renal toxicity and serum biochemical indicators of hepatic and renal functions. Additionally, activated partial thromboplastin time (APTT), prothrombin time (PT) and kidney and renal pathological changes were also observed.

RESULTCompared to injured skin rats, mercury contents of blood, urine and kidney were increased significantly in low, middle and high-dose BDSJS groups administered for consecutive 4 weeks. The levels of mercury showed decreases in urine (89%, 78%, 93%) and kidney (55%, 51%, 57%), and blood mercury concentration recovered to the normal range in low, middle and high-dose BDSJS groups after the drug withdrawal for 4 weeks. Kidney coefficient and beta2-MG were remarkably increased and renal tubular epithelial cell swelling could be found in the high-dose group, and kidney coefficient, beta2-MG and renal morphology basically recovered to the normal levels after the drug withdrawal for 4 weeks.

CONCLUSIONThe administration of BDSJS for consecutively 4 weeks can cause mercury accumulation in blood and mainly in kidney. Once the accumulated mercury concentration of kidney reaches a certain level, renal tubular epithelial cells would be injured. 1.1 mg x cm(-2) of BDSJS is proved to be safe and 2.2 mg x cm(-2) can cause mild but reversible injury in the function of kidney which can be recovered after drug withdrawal for 4 weeks.

Acetylglucosaminidase ; urine ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Female ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVETo investigate the antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction (, MDBD) on adraimycin-induced nephropathy in rats.

METHODSThirty-two male Sprague Dawley albino rats were randomly divided into 4 groups: the control, model, and two treatment groups, with 8 in each group. Nephropathy was induced in the latter 3 groups by intravenous injection of adriamycin. Rats in the two treatment groups received intragastric administration of benazepri (a positive control) or MDBD, which is composed of extracts of Radix Angelicae sinensis, Astragalus membranaceus (Fisch.) Bge and Rhizoma chuanxiong. Serum albumin, blood lipids, 24-h urine protein and urine N-acetyl-b-D-glucosaminidase (NAG) were measured every 2 weeks. The ratio of kidney to body weight was measured. The expressions of extracellular matrix proteins in the renal cortex, including colleagen IV (Col-IV) and fibronectin (FN), were examined by immunohistochemistry, and the transcription of genes encoding transforming growth factor β1 (TGF-β1), the tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 9 (MMP-9) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) at the end of the 8-week treatment.

RESULTSCompared with the untreated rats in the model group, MDBD significantly increased serum albumin, lowered the blood lipids and decreased the ratio of kidney to body weight. MDBD significantly reduced the excretion levels of urinary protein and NAG as well as the accumulation of extracellular matrix (ECM), including Col-IV and FN, in the renal cortex. Further, MDBD decreased TIMP-1 and TGF-β1 gene expressions and increased MMP-9 gene expression in the kidney.

CONCLUSIONSMDBD was effective in treating the rat model of nephropathy. The clinical benefit was associated with reduction of renal fibrosis. The antifibrotic effect of MDBD may be mediated through the regulation of TIMP-1, MMP and TGF-β1 gene expressions.

Acetylglucosaminidase ; urine ; Animals ; Body Weight ; drug effects ; Collagen Type IV ; metabolism ; Doxorubicin ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibronectins ; metabolism ; Fibrosis ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Kidney Cortex ; drug effects ; enzymology ; pathology ; physiopathology ; Kidney Diseases ; blood ; drug therapy ; physiopathology ; urine ; Kidney Function Tests ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triglycerides ; blood

OBJECTIVEThis study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.

METHODSRats were treated with either procyanidins or lycopene 2h before HgCl(2) subcutaneously injection, once daily treatment for 2 successive days.

RESULTSIn comparison with HgCl(2) group, markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to (18.45±11.63) mmol/L and (15.93±9.36) mmol/L, (4.54±0.78) g/(g·Cr) and (4.40±1.12) g/(g·Cr). N-acetyl-beta-D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase in urine were depressed to (125.49±11.68) U/(g·Cr), (103.73±21.79) U/(g·Cr), (101.99±12.28) U/(g·Cr), and (113.19±23.74) U/(g·Cr), (71.14±21.80) U/(g·Cr), (73.64±21.51) U/(g·Cr) in procyanidins and lycopene groups. Indicators of oxidative stress, for example, Glutathion was reduced to (45.58±9.89) μmol/(g·pro) and (45.33±5.90) μmol/(g·pro), and antioxidant enzymes such as superoxide dismutase, glutathione-peroxidase were enhanced to (43.07±10.97) U/(mg·pro) and (39.94±6.04) U/(mg·pro), (83.85±18.48) U/(mg·pro), and (85.62±12.68) U/(mg·pro). Malondialdehyde was lowered to (0.95±0.12) (μmol/g·pro) and (1.03±0.12) μmol/(g·pro) in procyanidins and lycopene groups. ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively. Pathological changes were much better as well.

CONCLUSIONProcyanidins and Lycopene play some protective role against mercury kidney damage.

Acetylglucosaminidase ; urine ; Alkaline Phosphatase ; urine ; Animals ; Antioxidants ; therapeutic use ; Blood Urea Nitrogen ; Carotenoids ; therapeutic use ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; prevention & control ; L-Lactate Dehydrogenase ; urine ; Lipid Peroxidation ; Malondialdehyde ; metabolism ; Mercuric Chloride ; pharmacokinetics ; toxicity ; urine ; Mercury ; metabolism ; Proanthocyanidins ; therapeutic use ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the renal injury in rats induced by Longdan Xiegan decoction (LDXGD) containing different dosages Aristolochia manshriensis.

METHODSD rats were divided into four groups at random, and were fed with three kinds of LDXGD 13, 14.5, 17.5 g x kg(-1) (containing respectively A. manshriensis 1.5, 3, 6 g x kg(-1)) and distilled water respectively for 12 weeks. Renal functional parameters on 4,8,12 w were determined and changes of histomorphology in rats on the end of experiment were observed.

RESULTThe LDXGD containing low dose (1.5 g x kg(-1)) A. manshriensis did't induce significantly renal injury in rats during 12 weeks; the LDXGD containing midst dose(3 g x kg(-1)) A. manshriensis induced light damage of proximal convoluted tubule epithelial cells in rats during 12 weeks; the LDXGD containing high dose(6 g x kg(-1)) A. manshriensis induced significantly renal injury in rats after administed 4 weeks. Along with the lasting of administration, the degree of injury became more seriously. The main renal injury location was in proximal convoluted tubule.

CONCLUSIONThe renal toxicity of LDXGD is correlated with the dose of A. manshriensis and the time of administration. The LDXGD containing low dose A. manshriensis has relative security. However, the LDXGD containing high dose A. manshriensis can induce renal injury.

Acetylglucosaminidase ; urine ; Animals ; Aristolochia ; chemistry ; toxicity ; Blood Urea Nitrogen ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; toxicity ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Kidney Tubules, Proximal ; drug effects ; pathology ; Male ; Plants, Medicinal ; chemistry ; toxicity ; Proteinuria ; chemically induced ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; beta 2-Microglobulin ; urine ; gamma-Glutamyltransferase ; urine