OBJECTIVETo investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.

METHODSRats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.

RESULTSHQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.

CONCLUSIONHQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Animals ; Apoptosis ; drug effects ; Body Weight ; drug effects ; Caspase 3 ; metabolism ; Chromatography, High Pressure Liquid ; Cytochromes c ; metabolism ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney ; drug effects ; pathology ; Kidney Diseases ; blood ; chemically induced ; complications ; drug therapy ; Kidney Glomerulus ; drug effects ; pathology ; ultrastructure ; Kidney Tubules ; drug effects ; pathology ; ultrastructure ; Male ; Membrane Proteins ; metabolism ; NF-KappaB Inhibitor alpha ; metabolism ; NF-kappa B ; metabolism ; Organ Size ; drug effects ; Proteinuria ; blood ; complications ; drug therapy ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo study the prevention effect of salidroside on contrast-induced-nephropathy (CIN) and its underlying mechanism.

METHODSA total of 24 Wistar rats were randomly divided into 4 groups with 6 in each group. Rats were firstly administrated with normal saline (control and model groups), N-acetylcysteine (NAC, NAC group) and salidroside (salidroside group) for 7 days before model establishment in each group, respectively. Histopathological analysis was performed by periodic acid-Schiff (PAS) staining. Oxidative stress related parameters including superoxide dismutase (SOD) and methane dicarboxylic aldehyde (MDA), nitric oxide (NO), angiotensin II (Ang II), 8-hydroxy-2'-deoxyguanosine (8-OHdG), mRNA and protein levels of endothelial nitric oxide synthase (eNOS), and nitric oxide synthase (NOS) activity were measured.

RESULTSCompared with the control group, the levels of MDA, Ang II and 8-OHdG were all significantly increased and levels of SOD, NO, and eNOS mRNA and protein were decreased significantly in the model group (P<0.05). Meanwhile, the NOS activity was also significantly decreased in the model group (P<0.05). In addition, the levels of these parameters were all improved in the NAC (P<0.05) and salidroside groups and no significant different was found between these two groups (P>0.05).

CONCLUSIONSalidroside can be the potential substitute of NAC to prevent CIN. The underlying mechanism may be associated with oxidative stress damage caused by contrast agents.

Acetylcysteine ; pharmacology ; Animals ; Contrast Media ; adverse effects ; Cytoprotection ; drug effects ; Glucosides ; pharmacology ; Kidney ; drug effects ; pathology ; Kidney Diseases ; chemically induced ; prevention & control ; Oxidative Stress ; drug effects ; Phenols ; pharmacology ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects

OBJECTIVETo investigate RANK-RANKL expression in the kidneys of a rat model of puromycin aminonucleoside nephropathy (PAN).

METHODSThirty-six SD rats were randomly divided into PAN model group and normal control group. PAN was induced by a single intravenous injection of 100 mg/kg puromycin aminonucleoside. Serum creatinine and 24-hour urinary protein were measured on days 3, 7, and 14 after the injection, and renal pathologies were assessed with optical and immune transmission electron microscopy. The expression of RANK and RANKL in the kidneys was examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.

RESULTSThe PAN model rats showed massive proteinuria and elevated serum creatinine on day 3, which peaked on day 7. RANK-RANKL protein and mRNA expressions in PAN model group was higher than those in the control group. In the PAN rats, RANK was expressed mainly on the top cell membrane and in the cytoplasm of renal podocytes with a significantly increased expression level compared with that in the control group.

CONCLUSIONThe PAN rat model shows aberrant RANK and RANKL expressions in the podocytes, indicating their contribution to podocyte injury in PAN.

Animals ; Creatinine ; blood ; Female ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Male ; Podocytes ; drug effects ; metabolism ; Proteinuria ; pathology ; Puromycin Aminonucleoside ; adverse effects ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor Activator of Nuclear Factor-kappa B ; metabolism

OBJECTIVETo explore the potential mechanisms of huangkui capsule (HKC), an extract from Abelmoschus manihot (AM), for ameliorating renal inflammatory injury by regulating p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with adriamycin-induced nephropathy (ADRN).

METHODNineteen Sprague-Dawley (SD) rats were randomly divided into three groups, the sham-operation group, the untreated model group,and the HKC-treated group. Rats in the untreated model group and the HKC-treated group were made into ADRN model by right nephrectomy and twice intravenous injections of adriamycin( ADR, 0.4 mL and 0.2 mL respectively within 4 weeks). After the model successfully established, rats in the HKC-treated group were orally given HKC (2 mg x kg(-1) per day), while rats in the untreated model group and the sham-operation group were intervened with distilled water respectively. The intervention for all rats was 4 weeks. Rats' body weight were weighted and 24 h urinary protein excretion (Upro) was detected at the end of the 1st, 2nd, 3rd, and 4th week after the intervention of HKC or distilled water. All rats were sacrificed at the end of the 8th week after nephrectomy, and then, to withdraw blood and kidney to examine the blood biochemical parameters, the glomerular morphological changes, alpha-smooth muscle actin (alpha-SMA) and collagen type I expressions,and the glomerular macrophages infiltration. Besides, the protein expression of transforming growth factor (TGF)-beta1, p38MAPK, as well as phosphorylated p38MAPK (p-p38MAPK) in renal tissues were detected by Western blotting.

RESULTAs compared with rats in the untreated model group, in the HKC-treated group,the HKC treatment significantly improved Upro, serum albumin, mesangial cell proliferation, extracellular matrix (ECM) and collagen deposition,and decreased the expression of alpha-SMA and collagen type I and the infiltration of ED1+ and ED3+ cells in glomeruli. In addition, it significantly down-regulated the protein expression of TGF-beta1 and p-p38MAPK in renal tissues.

CONCLUSIONHKC had the effects on ameliorating renal inflammatory injury in vivo. It could reduce the expression of TGF-beta1 and improve the infiltration and activation of inflammatory cells in glomeruli by way of intervening p38MAPK signaling pathway in kidney through down-regulating the protein expression of p-p38MAPK, as the key signal molecule.

Animals ; Collagen Type I ; metabolism ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Extracellular Matrix ; metabolism ; Kidney Diseases ; chemically induced ; drug therapy ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transforming Growth Factor beta1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA-induced renal injury in a setting of CsA-induced renal injury.
Animals ; Apoptosis/drug effects ; Chronic Disease ; Cyclosporine/*toxicity ; Immunosuppressive Agents/*pharmacology ; Intestines/drug effects/pathology ; Kidney Diseases/chemically induced/*pathology ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Sirolimus/*pharmacology

OBJECTIVETo observe the effects of Chailing Decoction (CD) on transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), renal cell apoptosis and proliferation in rats with chronic cyclosporine A nephropathy (CCN), and to explore its possible mechanism for inhibiting renal fibrosis.

METHODSThe CCN rat model was prepared using oral administration of cyclosporine A (CsA, 30 mg x kg(-1) x d(-1)). Meanwhile, they were treated with CD (3 g x kg(-1) x d(-1)) by gastrogavage. The serum blood urea nitrogen (BUN), serum creatinine (SCr), and creatinine clearance rate (CCr) were measured by the end of the fourth week of the experiment. The kidneys were taken out on the next day. The degree of renal fibrosis was detected using Masson staining. The protein and gene expressions of TGF-beta1, and CTGF were observed using immunohistochemical assay and RT-PCR. The renal cell apoptosis rate and the proliferation index were detected by flow cytometry.

RESULTSCompared with the control group (BUN: 6.123 +/- 0.588 mmol/L; SCr: 75.654 +/- 8.196 micromol/L; CCr: 0.539 +/- 0.169 mL/min), the renal function of the model group (BUN: 11.600 +/- 1.437 mmol/L; SCr: 101.985 +/- 10.809 micromol/L; CCr: 0.272 +/- 0.060 mL/min) obviously declined (P < 0.01). The collagen deposition in the renal interstitial area significantly increased. The protein and mRNA expressions of TGF-beta1, and CTGF in the tubular epithelial cells and the mesenchymal cells were significantly enhanced (P < 0.01). The cell proliferation index and the apoptosis rate both increased, but the ratio of apoptosis to proliferation (0.317 +/- 0.059) decreased more than that in the control group (0.680 +/- 0.150, P < 0.01). After treatment by CD, the renal function (BUN: 7.340 +/- 0.857; SCr: 84.923 +/- 10.627; CCr: 0.405 +/- 0.081) was significantly enhanced (P < 0.05, P < 0.01), the collagen deposition decreased, the high protein and mRNA expressions of TGF-beta1 and CTGF were down-regulated (P < 0.01), the ratio of apoptosis to proliferation increased (0.650 +/- 0.092, P<0. 01).

CONCLUSIONCD could improve the renal function of CCN model rats, inhibit the expressions of TGF-beta1 and CTGF, and recover the balance between the renal cell apoptosis and proliferation by inducing cell apoptosis and inhibiting cell proliferation, thus delaying the renal fibrosis process.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Connective Tissue Growth Factor ; metabolism ; Cyclosporine ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo study the effects of modified danggui buxue decoction (MDBD) on podocytes in adriamycin-induced nephropathy (DN) model rats.

METHODSSD rats were divided into four groups, i.e., the normal control group, the model group, the benazepril group, and the MDBD group. On the 7th, 28th, 42nd, and 56th day of modeling, the urine sample was collected to examine the dynamic changes of urinary albumin quantitation. The renal tissue was processed for the examinations under light microscope and electron microscope. The immunofluorescence of nephrin and podocin were detected. The expressions of the slit membrane expression protein in the renal tissue were further analyzed using RT-PCR and Western blot.

RESULTS(1) Urinary protein (UP): The UP did not obviously decrease in each treatment group on the 7th day, but it decreased so markedly on the 28th, 42nd, and 56th day. There was statistical difference in UP of the benazepril group and the MDBD group when compared with that of the model group (P < 0.05). The decrease was most obvious in the MDBD group. (2) Effects on the podocytes and the renal tissue:

RESULTSunder light microscope and electron microscope showed, when compared with the model group, the proliferation of mesangial cells, the renal tubule-interstitial lesion, the podocyte fusion, and the expressions of nephrin and podocin were milder, and the urinary albumin quantitation was more obviously reduced in the benazepril group and the MDBD group. But the renal fibrosis correlated renal pathological progress also existed, indicating the renal lesion degree was milder but could not be reversed. (3) Results of RT-PCR and Western blot: Statistical difference existed in the expressions of nephrin and podocin between the benazepril group and the MDBD group on the 56th day, when compared with the model group (P < 0.05).

CONCLUSIONMDBD showed therapeutic effects on adriamycin-induced nephropathy model rats. Its actions could be achieved through reducing albuminuria, inhibiting the proliferation of mesangial cells, attenuating the renal tubule-interstitial lesion, and protecting the integrity of the slit membrane structure.

Animals ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Kidney Diseases ; chemically induced ; pathology ; Male ; Podocytes ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity.

METHODSFemale Wistar rats were randomly assigned to control (3 groups, 6 rats in each) and treatment groups (3 groups, 6 rats in each). They were subjected to subcutaneous injections of DM (at doses of 0.003, 0.03, and 0.3 mg/kg bw/d) after 30, 45, and 60 d, respectively.

RESULTSSignificant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase (P≤0.05) of plasma MDA concentrations after 45 d. A significant increase (P≤0.05) in plasma ALT (after 45 and 60 d) and AST (after 60 d) concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages (P≤0.05), especially in the dominance of classes 3 and 4 of obtained comet.

CONCLUSIONDM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.

Animals ; Aspartate Aminotransferases ; metabolism ; Behavior, Animal ; drug effects ; Chemical and Drug Induced Liver Injury ; metabolism ; pathology ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Female ; Insecticides ; administration & dosage ; chemistry ; toxicity ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; pathology ; Liver ; drug effects ; Malondialdehyde ; Molecular Structure ; Nitriles ; administration & dosage ; chemistry ; toxicity ; Organ Size ; Oxidative Stress ; drug effects ; Pyrethrins ; administration & dosage ; chemistry ; toxicity ; Random Allocation ; Rats ; Urea ; blood ; Weight Gain ; drug effects

After 4-months of alpha interferon (IFN-alpha), a 64-year old woman with chronic hepatitis C developed a cough and dyspnea and showed diffuse infiltrative opacities on her chest X-ray. Her symptoms persisted after stopping the IFN-alpha therapy. Pulmonary function testing revealed a reduced forced vital capacity. High-resolution computed tomography of the lung showed peripheral and peribronchovascular ground glass attenuation and consolidation associated with reticulation. Bronchoalveolar lavage was performed for further evaluation and showed a lymphocyte level of 8.2%, an uncommon finding in IFN-alpha-induced interstitial pneumonitis. We performed a lung biopsy to diagnose her disease and it suggested interstitial pneumonitis. This was considered to be due to the immunomodulatory effects of INF-alpha. Although rare, any sign of significant pulmonary involvement should be evaluated.
Antiviral Agents/*adverse effects/therapeutic use ; Bronchoalveolar Lavage ; Female ; Hepatitis C, Chronic/complications/*drug therapy ; Humans ; Interferon-alpha/*adverse effects/therapeutic use ; Kidney Failure, Chronic/complications ; Lung Diseases, Interstitial/*chemically induced/pathology/radiography ; Middle Aged ; Respiratory Function Tests ; Tomography, X-Ray Computed

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