The Protective Role of Procyanidins and Lycopene Against Mercuric Chloride Renal Damage in Rats

Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In 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.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.

Protective effect of antioxidant on renal damage caused by Doxorubicin chemotherapy in mice with hepatic cancer

Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model.The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM(1 mg/kg·0.2 mL/2d).The model control group received normal saline(NS) of the same volume at the same time.1%TBHQ was added into the diet of mice of the antioxidant intervention group.Seven weeks later,morning urines and peripheral blood were randomly collected to detect UAIb,UCr,BUN,Scr and UAlb/Cr levels.All mice were beheaded.The renal tissues were made into homogenate,and SOD,T-AOC and MDA content in tissues were detected followed by cell lysis.All data were processed using SPSS 19.0.Results:The UAlb/Cr,BUN.Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD,T-AOC in doxorubicin chemotherapy group were lower than those of model control group(P<0.01).The UAlb/Cr,BUN,Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD,T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group(P<0.05).The BUN of model control group was higher than that of blank group,and T-AOC was lower than that of blank group,and difference was statistically significant(P<0.05).Conclusions:Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer.TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.

The Relationship Between the Energy Levels of Shock Waves and the Degree ofRenal Damage After ESWL：A Prospective Clinical Mat

In an attempt to understand the effects of high energy shock wave (HESW)on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups,using same voltage with different numbers of shock wave therapy to identify the difference of effects on renal function. Stone burdens and posit ion were similar in these groups. Each group received 1500, 2000, 2500 or 3000 puises at 12. 5 KV on JT-3lithotripotor respectively. All the groups had significantly increased the levels of urinary NAG, β2MG, ALB and serum β2MG, which reached the highest values on 1-3days after ESWL (P<0. 001), and then decreased to the pre-ESWL levels except urinary NAG in group Cand D and serum β2MG which were still significantly higher (P<0.05) than those before-ESWL on the 7th day after ESWL. There was significant correlation between either urinary NAG (γ=0. 977, P<0. 05) or β2MG (γ=0. 933, P<0. 001) with the number of shock wave. In addition, urinary NAG and β2MG increased significantly when the number of shock waves was over 2500 shots.These above findings suggest that shock wave had induced acute changes in renal functions and transient renal tubular damages, although these functional changes recovered within one week, and the tubular damage might last longer than 7 days , In order to avoid serious renal damage, it’s necessary to limit the energy level of shock waves under 12. 5 KV×2500 shots by using JT-3 lithotriptor.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4

BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.

Chimonanthus nitens Oliv. leaves flavonoids alleviate hyperuricemia by regulating uric acid metabolism and intestinal homeostasis in mice

This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric acid(UA),creatinine and blood urea nitrogen,downregulated hepatic mRNA expressions of xanthine oxidase(XO),phosphate ribose pyrophosphate synthetase(PRPS)and adenosine deaminase(ADA)in hyperuricemia mice.In addition,CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins.Finally,CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia.Besides,CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1(ZO-1),Occludin,mucin 2(MUC2)and mucin 4(MUC4),as well as decreased mRNA levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)in mice.Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus,Alistipes,Prevotellaceae_UCG-001 and Parasutterella.Overall,our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.

Study on the effect of lowering uric acid and effect on the kidney of Poriae cutis in hyperuricemia mice

Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueous solvent,HUA mice were established by hypoxanthine with potassium oxonate.Totally70 male Kunming mice were randomly divided into normal,model(500 mg/kg hypoxanthine+250 mg/kg potassium oxonate),Poriae cutis ethanol(PCE)and water extract(PCW)with high and low dose(388 mg/kg and 97mg/kg),benzbromarone(BEN)groups(7.5 mg/kg),all mice were administered with corresponding medication for 16 d.After the last administration,collected the 24 h urine volume,the urine uric acid(UUA)and urine creatinine(UCr)were determined.The morphological changes of the left kidney were viewed and the pathological changes in right kidneys were observed by hematoxylin-eosin(HE)staining.The serum contents of uric acid(SUA),creatinine(SCr)and urea nitrogen(BUN)were measured.Uric acid excretion index include fractional uric acid excretion(FEUA)and uric acid clearance rate(CUr)were calculated.The contents of OAT1,URAT1,GLUT9,TNF-αand IL-6 in the kidney were detected by ELISA.Results:PCE and PCW could increase UUA,UCr,FEUA,CUr and OAT1(P<0.05,P<0.01),reduce SUA,SCr,BUN,URAT1,GLUT9,TNF-αand IL-6(P<0.05,P<0.01).The pathological and morphological changes of kidneys in HUA mice were improved and the effect is better than BEN.Conclusion:Poriae cutis extractscould lower uric acid and possessed a protective effect on the kidney of mice with HUA,which was achieved by promoting uric acid excretion,regulating the expression of uric acid transporters and reducing the level of inflammatory factors.

Efficacy of Gold Nanoparticles against Nephrotoxicity Induced by Schistosoma mansoni Infection in Mice

Objective In this study, the ameliorative effects of gold nanoparticles （gold NP） on the renal tissue damage in Schistosoma mansoni （S. mansoni）-infected mice was investigated. Methods High-resolution transmission electron microscopy was used for the characterization of NP. The gold NP at concentrations of 250, 500, and 1000 μg/kg body weight were inoculated into 5. mansoni-infected mice. Results The parasite caused alterations in the histological architecture. Furthermore, it induced a significant reduction in the renal glutathione levels; however, the levels of nitric oxide and malondialdehyde were significantly elevated. The parasite also managed to downregulate KIM-I, NGAL, MCP-1, and TGF-8 mRNA expression in infected animals. Notably, gold NP treatment in mice reduced the extent of histological impairment and renal oxidative damage. Gold NP were able to regulate gene expression impaired by 5. Mansoni infection. Conclusion The curative effect of gold NP against renal toxicity in 5. mansoni-infected mice is associated with their role as free radical scavengers.

Relationship between Vesicoureteral Reflux and Glomerular Filtration Rate in Children

Vesicoureteral reflux(VUR)is one of the most common urinary tract anomalies in children and causes renal damage and studies focusing on the effect of VUR on renal function are rare.We recruited 35 primary VUR patients with recurrent urinary tract infection(UTI)and 10 non-VUR patients with recurrent UTI.Contrast-enhanced voiding urosonography(ceVUS)was performed for VUR grading,and renal dynamic imaging was used for evaluating glomerular filtration rate(GFR,mL/min).Standardized GFR(sGFR),namely GFR/BSA(mL·min-1·m-2),was calculated based on the body surface area(BSA).Total sGFR(tsGFR,mL·min-1·m-2)was obtained from the sum of sGFR on the left and right sides of all the children.The risk of renal regurgitation was equal in the unilateral reflux group.The sGFR of children with grade Ⅳ(45.74±18.05mL·min-1·m-2)and grade V(49.67±23.63mL·min-1·m-2)reflux was significantly lower than that in children with grade Ⅱ(77.69±22.21 mL·min-1·m-2).The renal function compensation of contralateral non-reflux kidney increased in unilateral reflux group,which was higher than that in the control group and level Ⅱ,Ⅳ and Ⅴ of reflux group respectively.In VUR group of the same grade,sGFR decreased with the age at diagnosis.In unilateral grade V refux group,the tsGFR was lower than that in the unilateral grade I reflux group(133.51±48.21 vs.186.87+53.49mL·min-1·m-2).The patients with VUR of unilateral grade Ⅱ were significantly older than those with VUR of unilateral grades Ⅱ and Ⅳ.This study indicates that severe VUR is significantly associated with decreased renal function.Therefore,VUR should be diagnosed early and managed individually.

Association between admission hemoglobin level and prognosis in patients with type 2 diabetes mellitus

BACKGROUND Anaemia is common in patients with chronic kidney disease(CKD)and is a major risk factor that contributes to mortality in such patients.Type 2 diabetes mellitus(T2DM)is one of the leading causes of CKD.The association between admission hemoglobin levels and renal damage in patients with T2DM remains unclear.AIM To evaluate the relationship between admission hemoglobin levels and prognosis in patients with T2DM.METHODS We performed a retrospective analysis of 265 consecutive patients presenting with T2DM between 2011 and 2015.The composite endpoint was end-stage renal disease or a 50%reduction in the estimated glomerular filtration rate.RESULTS In multivariable-adjusted Cox proportional hazards models(adjusting for demographic factors,traditional risk factors,lipids),the adjusted hazard ratios(HRs)for the highest and middle tertiles compared to the lowest tertile of hemoglobin were 0.82(95%CI:0.11-6.26,P=0.8457)and 0.28(95%CI:0.09-0.85,P=0.0246),respectively.However,after further adjustment for glycaemia control,hemoglobin was positively related to the risk of the composite endpoint(HR:1.05,95%CI:0.14-8.09,P=0.9602)when the highest tertile was compared to the lowest tertile of hemoglobin.We found a U-shaped relationship between hemoglobin levels and the composite endpoint.The curve tended to reach the lowest level at an optimal hemoglobin level.CONCLUSION Among patients with T2DM,a U-shaped relationship was observed between hemoglobin levels and renal damage.A lower admission hemoglobin level(hemoglobin<13.3 g/dL)is an independent predictor of renal damage.

Protective Effects of Combination of Radix Astragali and Radix Salviae Miltiorrhizae on Kidney of Spontaneously Hypertensive Rats and Renal Intrinsic Cells

Objective: To evaluate the effects of combination of Radix Astragali(RA) and Radix Salviae Miltiorrhizae(RS) on kidney of spontaneously hypertensive rats(SHRs) and renal intrinsic cells. Methods: SHRs were intragastrically administrated with RA(5.09 g/kg) and RS(2.55 g/kg) either alone or with combination for 4 weeks;valsartan(13.35 mg/kg) was used as a positive control. Blood pressure and renal ultrasonography were monitored periodically. The biomarkers [microalbumin(m ALB), cystatin C, angiotensin Ⅱ(Ang Ⅱ), interleukin-1 beta(IL-1β), and β2-microglobulin(β2-Mg), etc.] in serum and urine were measured by enzyme-linked immunosorbent assay(ELISA). The protein expressions [phosphorylated adenosine 5’-monophosphate-activated protein kinase-α1(p-AMPKα1), sestrin-β, calcium/calmodulin-dependent protein kinase kinase-β(Ca MKK-β), phosphoinositide 3-kinases(PI3 K), serine-threonine protein kinase 1(AKT1), and vascular endothelial growth factor receptor 2(VEGFR2)] in renal cortex were determined by Western blot. In vitro, the hypertensive cellular model was established by applying 2×10^-6 mol/L Ang Ⅱ. The primary human podocytes, human glomerular endothelial cells(HRGECs), and human proximal tubular epithelial cells(HK-2 s) were pre-incubated with sulfotanshinone sodium(Tan, 10 μg/m L) and/or calycosin-7-O-β-D-glucoside(Cal, 5 μg/m L). The cellular viability and apoptosis were assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) and Annexin V/PI staining, respectively. The level of endothelial nitric oxide synthase(eNOS) in culture supernatant was determined by ELISA. Results: RA+RS significantly decreased the diastolic blood pressure, renal vascular resistance index, and parenchymal thickness, increased 24 h urinary volume as well as lowered the levels of urine m ALB and serum cystatin C, IL-1β and β2-Mg of SHRs(P<0.05 vs. SHRs). The decreased protein levels of p-AMPKα1, sestrinβ and Ca MKK-β and the increased protein levels of PI3 K, AKT1 and VEGFR2 in renal cortex of SHRs were normalized after RA+RS treatment(P<0.05). In vitro, Tan and Cal attenuated the Ang Ⅱ-induced abnormal proliferation and increased the apoptosis of HRGECs and HK-2 s and improved the level of e NOS in culture supernatant. Whereas, neither of them showed powerful effect on podocyte. Conclusion: The combination of RA and RS had potential effects on alleviating the renal damages of SHRs and the renoprotection was independent of blood pressure level.

COVID-19 induced renal injury differs from that in other viral-infections

Background:Kidney injuries caused by several viral diseases have been reported worldwide among all age groups,races,and genders.Of particular importance is coronavirus disease 2019(COVID-19),and its prevalence in communities infecting all patient populations with symptoms ranging from asymptomatic to severe,including complications and mortality.Methods:Data were acquired from PubMed,Scopus,Google Scholar,Centers for Disease Prevention and Control(CDC),and Lexi-Comp using the following search terms:“COVID-19 and renal pathology,”“COVID-19 induced kidney disease,”“Viral infection induced kidney disease,”and“Viral infection induced renal damage.”Titles and abstracts were manually analyzed as per the exclusion and inclusion criteria of relevant articles;relevance of articles included studies on the pathology of a specific viral infection and the impact of the virus on the adult renal system.Results:The mechanisms for renal disease due to COVID-19 include direct renal tubular injury,cytokine storm,inflammation,thrombosis vs.acute tubular necrosis,thrombotic events,and direct renal injury.Although some mechanisms behind renal dysfunction among the studied viral infections are similar,the prevalence rates of kidney injury or damage differ.This might be described by recommended prophylactic and therapeutic approaches that can alter the viral infection characteristics and possibly the impact a particular organ system.Conclusion:The patient population at risk was old in age and had a high body mass index.The mechanisms associated with renal dysfunction are similar,including direct renal injury through angiotensin converting enzyme 2(ACE2)entry,inflammation,and thrombosis.The renal pathology of coronaviruses that differs from that of other prevalent viral infections is the activation of cytokine storm,which causes elevations of a greater number and different kinds of cytokines than other viral infections.

Characteristics of Mercury Intoxication Induced by Skin-lightening Products

Mercury is usually added to skin-lightening products due to its whitening effect.The Food and Drug Administration （FDA） limits the amount of mercury in cosmetics to trace amounts under 1 ppm.Nevertheless,many cosmetics contain mercury above 1000 ppm to increase the whitening effect.In a group of special patients in the study,pain,renal damage,and neuropsychiatric symptoms were the cardinal symptoms observed.