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Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.
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Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.
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Nephrotoxicity is a frequent and severe side effect of 5-fluorouracil (5-FU) chemotherapy which limits its use clinically regardless of being one of the most promising chemotherapeutic agents. Here, we assessed the nephroprotective activity of two structurally related phenolic acids 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) and gentisic acid (2,5 dihyroxybenzoic acid) against 5-FU induced nephrotoxicity in Wistar rats. Intraperitoneal administration of 5-FU at a dose of 20 mg/kg once a day for 5 days produced a significant elevation in serum parameters of the kidney such as uric acid, urea, creatinine, sodium and potassium levels along with severe histopathological changes in renal tissues of rats indicating severe nephrotoxicity. Administration of 2-pyrocatechuic acid (2-PCA) at 10, 30 and 100 by oral route for 9 days and additional 5 days with 5-FU resulted in an amelioration of altered serum parameters in a dose-dependent manner. Moreover, 2-PCA attenuated the renal damage produced by 5-FU demonstrating its efficacy as a nephroprotective agent for the prevention as well as amelioration of 5-FU induced nephrotoxicity. None of the doses of gentisic acid (GA) were found to be effective in this posology when given orally.
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Abstract Introduction: Aminoglycoside-induced acute kidney injury (AKI) is a pathology closely linked to oxidative and inflammatory reactions. Taking into account the previous reported antioxidant and anti-inflammatory effects of D-005, a lipid extract obtained from Cuban palm Acrocomia crispa (Arecaceae) fruits, this work aimed to evaluate the effects of D-005 on kanamycin-induced AKI. Methods: Male Wistar rats were divided into 7 groups: negative control (vehicle, Tween 65/H2O) and six groups treated with kanamycin to induce AKI: positive control (vehicle), D-005 (25, 100, 200, and 400 mg/kg) and grape seed extract (GSE, 200 mg/kg). D-005, vehicle, and GSE oral treatments were administered once daily for seven days, 1 h before kanamycin (500 mg/kg, i.p.). Serum uric acid and urea concentrations, renal histopathology, and oxidative markers (malondialdehyde (MDA), sulfhydryl (SH) groups, and catalase (CAT) activity) were assessed. Results: D-005 significantly reduced uric acid and urea levels, starting from D-005 100 mg/kg. Histopathologically, D-005, at all the tested doses, protected renal parenchyma structures (glomeruli, proximal tubules, and interstitium). These findings were accompanied by a significant reduction of MDA and SH group concentrations as well as restoration of CAT activity. The highest percentages of inhibition were obtained with the dose of 400 mg/kg. GSE, the reference substance, also prevented kanamycin-induced biochemical and histopathological changes, as well as reduced MDA and SH groups and restored CAT activity. Conclusion: The administration of repeated oral doses of D-005 significantly protected against kanamycin-induced AKI, which could be associated with the antioxidant and anti-inflammatory effects of this extract.
Resumo Introdução: Lesão renal aguda induzida por aminoglicosídeos é uma patologia intimamente ligada a reações oxidativas e inflamatórias. Considerando efeitos antioxidantes e anti-inflamatórios relatados anteriormente do D-005, um extrato lipídico de frutos da palmeira cubana Acrocomia crispa (Arecaceae), este trabalho avaliou efeitos do D-005 na LRA induzida por canamicina. Métodos: Dividiu-se ratos Wistar machos em 7 grupos: controle negativo (veículo, Tween 65/H2O) e seis grupos tratados com canamicina para induzir LRA: controle positivo (veículo), D-005 (25, 100, 200, 400 mg/kg) e extrato de semente de uva (ESU, 200 mg/kg). D-005, veículo, e tratamentos orais com ESU foram administrados uma vez por dia durante sete dias, 1 h antes da canamicina (500 mg/kg, i.p.). Avaliou-se concentrações séricas de ácido úrico e ureia, histopatologia renal e marcadores oxidativos (malondialdeído (MDA), grupos sulfidrila (SH), atividade de catalase (CAT)). Resultados: D-005 reduziu significativamente níveis de ácido úrico e ureia, partindo de D-005 100 mg/kg. Histopatologicamente, D-005, em todas as doses testadas, protegeu estruturas do parênquima renal (glomérulos, túbulos proximais e interstício). Estes achados foram acompanhados por uma redução significativa das concentrações de MDA e grupo SH, e pela restauração da atividade CAT. As maiores porcentagens de inibição foram obtidas com a dose de 400 mg/kg. ESU, a substância de referência, também evitou alterações bioquímicas e histopatológicas induzidas por canamicina, reduziu MDA e grupos SH e restaurou atividade CAT. Conclusão: A administração de doses orais repetidas de D-005 protegeu significativamente contra LRA induzida por canamicina, que pode estar associada aos efeitos antioxidantes e anti-inflamatórios deste extrato.
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Objective To evaluate the effect and mechanism of terminal fucosylation inhibitor 2-deoxy-D-galactose (2-D-gal) on ciclosporin (CsA)-induced renal epithelial-mesenchymal transition (EMT). Methods Fifteen male C57BL/6 mice aged 8-10 weeks were randomly and evenly divided into the control group (Ctrl group), CsA group and CsA+2-D-gal group (n=5). The expression levels of fucosyltransferase 1 (FUT1), EMT-associated proteins including E-cadherin, Vimentin, α-smooth muscle actin (α-SMA) in the kidney tissues of the Ctrl and CsA groups were detected by Western blot. The expression levels of terminal fucose in the kidney tissues of Ctrl and CsA groups were determined by immunofluorescence. The renal fibrosis of mice in each group was evaluated by Masson staining. The blood urea nitrogen and serum creatinine levels of mice in each group were detected. The in vitro EMT model of renal tubular epithelial cell HK2 was induced by CsA. HK2 cells were stimulated with 0, 2.5, 5.0 and 10.0 μmol/L CsA for 24 h, respectively. In addition, HK2 cells were divided into the Ctrl, 2-D-gal, CsA and CsA+2-D-gal groups. The morphology of HK2 cells after stimulation with different concentrations of CsA and in each group was observed. The expression levels of FUT1, E-cadherin, Vimentin and α-SMA in HK2 cells after stimulation with different concentrations of CsA and in each group were detected by Western blot. The expression level of terminal fucose in HK2 cells of the Ctrl and CsA groups was measured by immunofluorescence. Results Compared with the Ctrl group, the relative expression of E-cadherin protein was down-regulated, those of FUT1, Vimentin and α-SMA proteins were up-regulated (all P < 0.05), and that of terminal fucose in the mouse kidney tissues was up-regulated in the CsA group. Compared with the Ctrl group, the blood urea nitrogen and serum creatinine levels in the CsA and CsA+2-D-gal groups were up-regulated (all P < 0.05). Compared with the CsA group, the blood urea nitrogen and serum creatinine levels in the CsA+2-D-gal group were down-regulated (both P < 0.05). Compared with the Ctrl group, the collagen fiber deposition was increased and the relative expression of α-SMA protein was up-regulated in the mouse kidney tissues of CsA and CsA+2-D-gal groups (all P < 0.05). Compared with the CsA group, the collagen fiber deposition was decreased and the relative expression of α-SMA protein in the mouse kidney tissues was down-regulated in the CsA+2-D-gal group (both P < 0.05). With the increase of CsA concentration, the morphology of HK2 cells gradually became longer and thinner from original normal cobblestone shape, the relative expression levels of FUT1, Vimentin and α-SMA protein in HK2 cells were up-regulated, and that of E-cadherin protein was down-regulated in a concentration-dependent manner. Compared with the Ctrl group, the expression level of terminal fucose of HK2 cells was up-regulated in the CsA group. After CsA treatment combined with 2-D-gal intervention, the morphology of HK2 cells in the CsA+2-D-gal group was restored to resemble that of normal HK2 cells. Compared with the CsA group, the relative expression of E-cadherin protein in HK2 cells was up-regulated, whereas those of Vimentin and α-SMA proteins were down-regulated in the CsA+2-D-gal group (all P < 0.05). Conclusions CsA may induce EMT both in vivo and in vitro, and the terminal fucosylation is increased. 2-D-gal may inhibit CsA-induced EMT by suppressing the terminal fucosylation.
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ABSTRACT Objective: To explore the protective effects of curcumin against renal injury induced by formaldehyde in rats. Methods: A total of 21 male Sprague-Dawley rats were included. The animals were divided into three groups. The control group received 10 ml/kg of physiological saline intragastrically and intraperitoneally on a daily basis. The formaldehyde group were given 10 ml/kg of physiological saline intragastrically plus 10 mg/kg of formaldehyde intraperitoneally. The formaldehyde + curcumin group received 10 mg/kg of intraperitoneal formaldehyde daily as well as 100 mg/kg of curcumin intragastrically. After the completion of 14 days, the kidneys were removed. Tissue microscopic examination was performed with haematoxylin-eosin and periodic acid-Schiff staining. Also, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) activities, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured in tissue samples. Results: Formaldehyde induced renal injury. The degenerative tissue changes in the formal-dehyde + curcumin group seemed to regress, exhibiting similar characteristics to those of the controls. MDA, XO and NO were significantly higher in formaldehyde group than in controls, while a significant reduction occurred in SOD, CAT and GSH-Px activities in the formaldehyde group. Also, renal tissue MDA, XO and NO were significantly lower in the formaldehyde + curcumin group than in the formaldehyde group, while tissue SOD, CAT and GSH-Px activities were significantly higher. Conclusion: Curcumin improved the formaldehyde-induced renal degeneration. Also, curcumin was found to prevent the reduction in SOD, CAT and GSH-Px activities, while preventing MDA, XO and NO levels, exhibiting a protective effect against the formaldehyde-induced oxidative renal injury.
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This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury
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Animals , Male , Mice , Flavonoids , Antioxidants/analysis , Wounds and Injuries/classification , Blood Urea Nitrogen , Catalase/adverse effects , Tumor Necrosis Factor-alpha , Sepsis/chemically induced , Nitric Oxide Synthase/pharmacology , Creatinine , KidneyABSTRACT
In view of the increasing risk of arsenic on human health, the present study has been carried out to investigate the hepato-protective effect of piperine on arsenic induced-hepatic and renal toxicity in mice. Various oxidative stress parameter, antioxidant level and micro nutrients were analyses in hepatic and hepatic renal organ of mice. Methods: Mice exposed arsenic (sodium arsenate 5 mg/kg body weight p.o. for 45 days) caused a significant increases oxidative stress in hepatic and renal tissue as compared to controls group. Results: Abnormal levels of arsenic in hepatic and renal tissue increased the levels of ROS, LPO, and decreased the levels of GSH with SOD, CAT, and GPx activities in the hepatic and renal tissue of mice as compared to controls. Co-treatment of arsenic with piperine (1.5 mg/kg body weight p.o. for 45 days) decreased the levels of ROS, LPO, and increased the level of GSH, also increased SOD, CAT, and GPx activity and showed improvements in hepatic and renal tissue of mice as compared to arsenic-treated groups. Conclusion: Our results proved that piperine worked as antioxidant, anti- inflammatory in nature.
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Objective: To explore the mechanism of renal toxicity of Tripterygii Radix et Rhizoma by establishing the active component-target, protein interaction, biological function and pathway network corresponding to the target, and using molecular docking technology. Method: The traditional Chinese medicine(TCM) systems pharmacology database(TCMSP) and the comparative toxicogenomics database (CTD) were used to screen The toxic candidate compounds.In PubChem database, convert all candidate compounds into standard Canonical SMILES format, SMILES format file import SwissTargetPrediction platform, target prediction, will be the target of the corresponding compounds in TCMSP supplement with uniprot converts protein antipodal gene name, and from the human genome database (GeneCards) seek to compare the renal related gene protein,overlapping proteins were screened as potential renal toxicity targets of Tripterygii Radix et Rhizoma.Cytoscape software was used to construct the candidate components-target network of Tripterygii Radix et Rhizoma.Cytoscape software was combined with String database to draw the protein interaction network, DAVID platform was used to analyze the biological function of the target and the pathways involved, and Glide software was used to verify the combination of the key protein and the candidate components of tripterygiumwildiitoxicity. Result: The screening of 30 kinds of candidates for toxic ingredients of Tripterygii Radix et Rhizoma, involving 209 renal toxicity targets, network analysis results showed that Tripterygii Radix et Rhizoma by amino acid metabolism,phospholipid metabolism, catecholamine metabolism, inhibiting renal organic anion transporter Oatl, Oat2, Oat3 function, and inducing apoptosis, and participate in the mitogen-activated protein kinase(MAPK) signaling pathways, JAK-STAT signaling pathway,vascular endothelial growth factor(VEGF)signaling pathways,Toll-like receptor signaling pathway,ERBB signaling pathway, FcεRI signaling pathway, peroxisome proliferators-activated receptors(PPAR) signaling pathway such as toxic to the kidneys. Conclusion: The mechanism of kidney toxicity of Tripterygii Radix et Rhizoma was explored by using the characteristics of multi-component, multi-target and multi-pathway of TCM, which provided new ideas and methods for further research on the mechanism of kidney toxicity of Tripterygii Radix et Rhizoma.
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BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.
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Adult , Female , Humans , Acute Kidney Injury , Chronic Disease , Diagnosis , Fanconi Syndrome , Health Promotion , Herbal Medicine , Hospitalization , Incidence , Kidney Failure, Chronic , Korea , Medicine, East Asian Traditional , Medicine, Traditional , Nausea , Organization and Administration , Postpartum Period , Prognosis , United States Food and Drug Administration , VomitingABSTRACT
Objective To compare the renal toxicity of vancomycin with continuous infusion vs intermittent infusion. Methods The databases of EMBASE,PUBMED,the Cochrane Register of Controlled Trials,CBM,CNKI and WanFang were searched.The Cochrane Revman5.2 software was used for Meta-analysis.Results Two RCTs and eight observational studies were included in the systematic literature search with total of 1 764 patients.1 037 patients received vancomycin with continuous infusion while 727 patients with intermittent infusion.The Meta-analysis indicated that there was no significant difference in renal toxicity between continuous infusion group and intermittent infusion group(P>0.05).Conclusion Vanco-mycin continuous infusion cannot effectively reduce the incidence of renal toxicity.
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Objective To study the renal toxic effect of titanium dioxide nanoparticles (TiNPs) prepared by chemical and green route. Methods TiNPs were prepared by chemical (sol gel technique) and green route (using aqueous extract of Desmodium gangeticum root by using titanium tetraisopropoxide as precursor). Thus prepared TiNPs were characterized using UV–visible spectrophotometry, X-ray diffractometry and evaluated its renal toxic impact in different experimental models viz., Wistar rats (100 mg/kg b.wt.; oral), LLC-PK1 cells (100 mg/mL) and isolated renal mitochondria (0.25, 0.5 and 1 mg/mL). Results Compared to the chemically synthesized TiNPs, Desmodium gangeticum synthesized nanoparticles showed less nephrotoxicity, determined by elevated serum renal markers like urea (62%), creatinine (35%), aspartate aminotransferase (61%) and alanine transaminase (37%) and the result was in agreement with cellular toxicity (measured by MTT assay and lactate dehydrogenase activity). Further toxicity evaluation at the level of mitochondria showed not much significant difference in TiNPs effect between two synthetic routes. Conclusions The biochemical findings in renal tissue and epithelial cell (LLC-PK1) supported by histopathology examination and isolated mitochondrial activity showed minor toxicity with TiNPs prepared by green route (TiNP DG) than TiNP Chem.
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Objective:To study the renal toxic effect of titanium dioxide nanoparticles (TiNPs)prepared by chemical and green route.Methods:TiNPs were prepared by chemical (sol gel technique) and green route (using aqueous extract of Desmodium gangeticum root by using titanium tetraisopropoxide as precursor).Thus prepared TiNPs were characterized using UV-visible spectrophotometry,X-ray diffractometry and evaluated its renal toxic impact in different experimental models viz.,Wistar rats (100 mg/kg b.wt.;oral),LLC-PK1 cells (100 mg/mL) and isolated renal mitochondria (0.25,0.5 and 1 mg/mL).Results:Compared to the chemically synthesized TiNPs,Desmodium gangeticum synthesized nanoparticles showed less nephrotoxicity,determined by elevated serum renal markers like urea (62％),creatinine (35％),aspartate aminotransferase (61％) and alanine transaminase (37％) and the result was in agreement with cellular toxicity (measured by MTT assay and lactate dehydrogenase activity).Further toxicity evaluation at the level of mitochondria showed not much significant difference in TiNPs effect between two synthetic routes.Conclusions:The biochemical findings in renal tissue and epithelial cell (LLC-PK1)supported by histopathology examination and isolated mitochondrial activity showed minor toxicity with TiNPs prepared by green route (TiNP DG) than TiNP Chem.
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OBJECTIVE: To discuss the feasibility of renal toxicity screening of drugs using high content analysis technology. METHODS: Rosiglitazone was selected as the negative drug and valinomycin was selected as the positive drug. High intension HK-2 renal cell toxicity screening model was established through testing five indexes including cell number, DNA intensity, cell permeability, mitochondrial membrane potential and cytochrome C, using high content analysis technology. Aristolochic acid A and cisplatine that has obvious renal toxicity was used to validate the model. RESULTS: Valinomycin, cisplatin and aristolochic acid A has obvious renal toxicity;rosiglitazone don't have renal toxicity. CONCLUSION: High content analysis can be used to screen renal toxicity of drugs.
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Objective To investigate the Shenmai injection for the inhibition of hepatic and renal toxicity and leukocyte disorder during chemoradiotherapy in the women with advanced breast cancer. Methods 58 cases of female breast cancer patients with stage Ⅳ were selected and randomly divided into 2 groups, 29 cases of each group, and patients were treated with 5-hydroxytryptamine (5-HT3) receptor antagonists and white blood cell growth hormone and other conventional therapy, the control group received gemcitabine plus cisplatin chemotherapy, 28d for 1 cycles, the treatment group received more with Shenmai injection, interval was 15d, 2 groups were treated for 3 cycles. Levels of peripheral blood T lymphocyte subsets, cytokine levels and liver and kidney function, quality of life and clinical efficacy were compared. Results Compared with before treatment, levels of CD3+, CD4+ and CD4+/CD8+ in control group decreased (P<0.05), levels of CD3+, CD4+ and CD4+/CD8+ in treatment group increased (P<0.05), levels of CD8+ decreased(P<0.05), levels of IFN-γ, IL-2 and TNF-α increased(P<0.05), levels of IL-6 decreased(P<0.05), scores of KPS increased(P<0.05), scores of FACT-B decreased(P<0.05), levels of ALT, AST, BUN increased(P<0.05), and levels of CCr, WBC counts decreased(P<0.05), and compared with the control group, levels of CD3+ , CD4+ and CD4+/CD8+ in the treatment group were higher(P<0.05), levels of CD8+ were lower(P<0.05), levels of IFN-γ, IL-2 and TNF-α were higher(P<0.05), levels of IL-6 were lower(P<0.05), and the total efficiency was higher(P<0.05), levels of ALT, AST, BUN were lower (P<0.05), and levels of CCr, WBC counts were higher (P<0.05). After treatment, the efficacy of treatment group was higher than that of control group(Z=-2.142,P=0.032<0.05). Conclusion Shenmai injection can improve the efficacy of radiotherapy and chemotherapy in patients with advanced breast cancer, and it can effectively inhibit the liver and kidney damage and leukocyte disorder.
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Objective To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on the cyclosporin (CsA)-induced proliferation and apoptosis of glomerular mesangial cells in rat models. Methods The glomerular mesangial cells induced by different doses of CsA were treated with different doses of ATRA. MTT assay was carried out to detect cell proliferation. Hoechst 33258 fluorescent staining was adopted to observe the morphology of the apoptotic cells. Flow cytometry was conducted to detect the cellular apoptosis rate. Immunofluorescent staining was employed to quantitatively measure the expression level of mitochondria-derived pro-apoptotic Smac protein. Results Compared with the control group, administration of CsA at a dose of 0.5 μg/mL and above could suppress cellular proliferation, and use of CsA at a dose of 1.0 μg/mL and above could induce cellular apoptosis. The expression level of Smac protein was significantly up-regulated by CsA administration with a dose and time dependence (all P<0.05).Compared with the CsA group, combined administration of CsA and ATRA exerted a more significant inhibitory effect on cellular proliferation. Supplement of ATRA could significantly inhibit glomerular mesangial cellular apoptosis induced by CsA and down-regulate the expression of Smac protein with a dose dependence (both P<0.05). Conclusions CsA can inhibit cellular proliferation, induce cellular apoptosis and up-regulate the expression of Smac protein of glomerular mesangial cells. ATRA is capable of suppressing glomerular mesangial cellular apoptosis induced by CsA, which is probably mediated by the Smac signaling pathway.
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PURPOSE: Tenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF. MATERIALS AND METHODS: We prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C. RESULTS: The eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m²) to 144 wks (89.0±14.7 mL/min/1.73 m²) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m² vs. 98.4 mL/min/1.73 m², p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m² in eGFR (MDRD) at 144 wks. CONCLUSION: These data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.
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Humans , Creatinine , Diet , Follow-Up Studies , Glomerular Filtration Rate , HIV , HIV-1 , Plasma , Prospective Studies , Retrospective Studies , TenofovirABSTRACT
Objective To evaluate the renal toxicity of vancomycin hydrochloride and irbesartan tablets using the zebrafish model. Methods After construction of AB zebrafish kidney model, the fish were treated with drug after fertilization 2 days (2 dpf) to 5 dpf. At the end of the experiment, the number of renal edema zebrafish was counted in each experimental group to evaluate the renal toxicity of drugs. Results The zebrafish development was normal and no obvious toxicity at the dose of 16?4 ng/fish (1/10 MNLD) for vancomycin, and zebrafish renal edema occurred rate was 3?3%, 10% and 10% respectively at the dose of 54?7 ng/fish (1/3 MNLD), 164 ng/fish (MNLD) and 273 ng/fish ( LD10 ) with the death rate of 0%, 0% and 16?7%, respectively, which indicated that there was significant renal toxicity of vancomycin at the dose of 54?7 ng/fish (1/3MNLD) to 273 ng/fish (LD10). Irbesartan didn’t induce renal toxicity at the dose of 8?3 μg/mL (1/10 MNLC) to 91 μg/mL (LC10). Conclusions The zebrafish model of renal toxicity can be used for the early evaluation of drug renal toxicity and we made evaluation of the renal toxicity of vancomycin and irbesartan with this model.
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OBJECTIVE To observe and compare the cytotoxicity induced by andrographolide (AD)and its water soluble derivatives:andrographolide sodium bisulfite(ASB),active pharmaceutical ingredients of Chuanhuning and Yanhuning on human renal tubular epithelial cells (HK-2),and to explore the ASB-induced endoplasmic reticulum stress(ERS)mechanism. METHODS HK-2 cells were treated with the above four drugs respectively. The survival rate was examined by methyl thiazolyltetrazolium (MTT) assay and 50% inhibitory concentration (IC50) was calculated. In ASB treated group, Hoechst33342 staining and flow cytometry analysis were used to determine cell apoptosis, intracellular superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were examined, and the protein expressions of binding immunoglobulin protein (Bip),C/EBP-homologous protein (CHOP)and cysteine-containing aspartate-specific protease 4(caspase 4)were detected by Western blotting. RESULTS The four drugs inhibited HK-2 cell growth in a time-dependent and concentration-dependent manner. At 24 h,the IC50 of AD (30.6 μmol · L- 1) was lower than that of others. Active pharmaceutical ingredients of Chuanhuning and Yanhuning (16.2 and 15.6 mmol · L- 1) were very close,ASB was 29.4 mmol · L-1. ASB(0,15,30 and 60 mmol · L-1)increased the apoptotic rate and caused the decrease in SOD activity and the increase in MDA content in a dose-dependent manner. Compared with control group,the protein expression of CHOP increased (P<0.01) at 8 h with ASB (30 and 60 mmol · L-1)treatment,Bip and caspase 4 had no significant change. In addition,at 24 h, ASB(60 mmol·L-1) decreased the expression of Bip(P<0.05),ASB(30 and 60 mmol·L-1)promoted the expression of CHOP(P<0.01),and the protein expression of activated caspase 4 increased in a concentration-dependent manner(P<0.01). CONCLUSION AD and its water soluble derivatives have a toxic effect on HK-2 cells. CHOP and caspase 4 pathway related to ERS is involved in ASB-induced apoptosis.
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Aim: The aim of this study was to examine the effect of ethanolic extract of coriander leaves as a potent in vivo antioxidant agent in an effort of finding possible sources of antioxidants for future use in food and pharmaceutical formulations. Study Design: Randomized controlled experiment. Place and Duration of Study: Experimental Animal Unit, Drug Radiation Research Department, National Center for Radiation Research and Technology, Cairo Egypt. Methodology: Antioxidant activity of ethanol extract of coriander leaves was estimated by oxidative stress induced by radiation exposure with the dose of 4 Gy, Silymarin was used as a reference antioxidant drug in female albino rat. Results: Results of experiment revealed that radiation exposure caused a significant increase in serum caspase3 (0.870± 0.086), alanine transaminase (ALT) activity (24.43± 5.02) as well as urea (42.53± 6.11) and creatinine (0.865± 0.064) levels with an increase in liver and kidney lipid peroxidation (MDA) (307.0± 29.22 & 285.5± 48.93) respectively, while decrease in serum albumin (3.003± 0.355), protein (8.66± 0.436) as well as glutathione (GSH) contents of liver and kidney tissues (63.24± 12.19 & 17.38± 1.414) were estimated respectively. In addition serum globuline level and albumin /globuline ratio showed no significant changes. On the other hand, the administration of coriander (600 mg/kg bw) and silymarin (70 mg/kg bw) pre-treatment effectively prevented these alterations and maintained the antioxidant status. Conclusion: Data from present results revealed that Coriandum Sativum act as an antioxidant agent due to its free radical scavenging and cytoprotective activity.