Protective Effect of Salvia Przewalskii Extract on Puromycin-Induced Podocyte Injury

2015 ◽  
Vol 42 (3) ◽  
pp. 216-227 ◽  
Author(s):  
De-shu Dai ◽  
Xiang Liu ◽  
Yang Yang ◽  
Xiao-mei Luo ◽  
Ren-xian Tang ◽  
...  
Keyword(s):  
Total Phenolic ◽  
High Dose ◽  
Mrna Levels ◽  
Treatment Results ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury ◽  
Pas Staining ◽  
Foot Process ◽  
Glomerular Morphology ◽  
Medium Dose

Background: To determine the effect of Salvia przewalskii extract (SPE) from total phenolic acids on puromycin aminonucleoside (PAN)-induced rat podocyte injury. Methods: The rats were divided into groups that were treated with either PAN only or PAN followed by tacrolimus or SPE. We evaluated the effects of SPE on podocyte injury 5, 10, 15 and 21 days following treatment. Results: (1) Proteinuria was observed starting on day 5 in all groups. The peak levels of proteinuria differed among the groups with tacrolimus and high-dose SPE, which significantly decreased proteinuria relative to the PAN and low- and medium-dose SPE groups. The proteinuria in each group decreased by day 15 and returned to a normal level by day 21. (2) H&E and PAS staining revealed no abnormality in glomerular morphology. With electron microscopy, we observed foot process effacement in the rats of all groups starting on day 5, but rats in the tacrolimus and high-dose SPE groups exhibited a lower degree. (3) IHC staining of nephrin and podocin revealed unaffected expression and better linear distributions in the high-dose SPE and tacrolimus groups. Western blot analysis confirmed that SPE could improve the expression of proteins. (4) The mRNA levels of nephrin and podocin in the tacrolimus and high-dose SPE groups were significantly higher than that in the others. Conclusion: In our study, we first demonstrated the ability of SPE to reduce proteinuria, preserve the morphology and structure of podocytes and retain the levels of slit diaphragm proteins on PAN-induced rat podocytes injury.

scholarly journals Amino acid transport in podocytes

2000 ◽  
Vol 278 (6) ◽  
pp. F999-F1005 ◽  
Author(s):  
Joachim Gloy ◽  
Steffen Reitinger ◽  
Karl-Georg Fischer ◽  
Rainer Schreiber ◽  
Anissa Boucherot ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury ◽  
Process Formation ◽  
Foot Process ◽  
Transporter Systems ◽  
Constant Source

It has recently been shown that formation of podocyte foot processes is dependent on a constant source of lipids and proteins (Simons M, Saffrich R, Reiser J, and Mundel P. J Am Soc Nephrol 10: 1633–1639, 1999). Here we characterize amino acid transport mechanisms in differentiated cultured podocytes and investigate whether it may be disturbed during podocyte injury. RT-PCR studies detected mRNA for transporters of neutral amino acids (ASCT1, ASCT2, and B0/+), cationic AA (CAT1 and CAT3), and anionic AA (EAAT2 and EAAT3). Alanine (Ala), asparagine, cysteine (Cys), glutamine (Gln), glycine (Gly), leucine (Leu), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), glutamic acid (Glu), arginine (Arg), and histidine (His) depolarized podocytes and increased their whole cell conductances. Depletion of extracellular Na+ completely inhibited the depolarization induced by Ala, Gln, Glu, Gly, Leu, and Pro and decreased the depolarization induced by Arg and His, indicating the presence of Na+-dependent amino acid transport. Incubation of podocytes with 100 μg/ml puromycin aminonucleoside for 24 h significantly attenuated the effects induced by the various amino acids by ∼70%. The data indicate the existence of different amino acid transporter systems in podocytes. Alteration of amino acid transport may participate in podocyte injury and disturbed foot process formation.

Prolactin stimulates food intake in a dose-dependent manner

1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz
Keyword(s):  
Food Intake ◽  
Female Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Additional Control ◽  
The Mean ◽  
Ovine Prolactin ◽  
Dose Dependent ◽  
Medium Dose ◽  
Cumulative Food Intake

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.

Systemic administration of naked plasmid encoding HGF attenuates puromycin aminonucleoside-induced damage of murine glomerular podocytes

2011 ◽  
Vol 301 (4) ◽  
pp. F784-F792 ◽  
Author(s):  
Xuan Bu ◽  
Yang Zhou ◽  
Hua Zhang ◽  
Wenjing Qiu ◽  
Lu Chen ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Gene Transfection ◽  
Systemic Administration ◽  
Renal Diseases ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury ◽  
Rapid Injection ◽  
Naked Plasmid

Podocyte injury is considered to play important roles in the pathogenesis of human glomerular disease. There is accumulating evidence suggesting that hepatocyte growth factor (HGF) elicits preventive activity for glomerular cells in animal models of chronic renal diseases. In this study, we demonstrated that delivery of a naked plasmid vector encoding the human HGF gene into mice by a hydrodynamic-based in vivo gene transfection approach markedly reduced proteinuria and attenuated podocyte injury in a mouse model induced by puromycin aminonucleoside (PAN) injection. Systemic administration by rapid injection via the tail vein of a naked plasmid containing HGF cDNA driven under a cytomegalovirus promoter (pCMV-HGF) produced a remarkable level of human HGF protein in the circulation. Tissue distribution studies suggested that the kidney expressed a high level of the HGF transgene. Meanwhile, compared with tubules and interstitium, a higher level of exogenous HGF protein was detected in the glomeruli. Administration of pCMV-HGF dramatically abated the urine albumin excretion and podocyte injury in PAN nephropathy in mice. Exogenous expression of HGF produced evidently beneficial effects, leading to restoration of Wilms' tumor-1 (WT1) and α-actinin-4 expression and attenuation of ultrastructural damage of the podocytes. In vitro, HGF not only restored WT1 and α-actinin-4 expression but also inhibited albumin leakage of podocytes incubated with PAN in a Transwell culture chamber. These results suggest that HGF might provide a novel strategy for amelioration of podocyte injury.

scholarly journals Paradoxical Regulation of Biotin Utilization in Brain and Liver and Implications for Inherited Multiple Carboxylase Deficiency

2004 ◽  
Vol 279 (50) ◽  
pp. 52312-52318 ◽  
Author(s):  
Diana Pacheco-Alvarez ◽  
R. Sergio Solórzano-Vargas ◽  
Roy A. Gravel ◽  
Rafael Cervantes-Roldán ◽  
Antonio Velázquez ◽  
...  
Keyword(s):  
High Dose ◽  
Mrna Levels ◽  
Holocarboxylase Synthetase ◽  
Biotin Deficiency ◽  
Multiple Carboxylase Deficiency ◽  
Regulatory Impact ◽  
Normal Metabolism ◽  
Liver And Kidney ◽  
Essential Function ◽  
The Brain

Holocarboxylase synthetase (HCS) catalyzes the biotinylation of five carboxylases in human cells, and mutations of HCS cause multiple carboxylase deficiency (MCD). Although HCS also participates in the regulation of its own mRNA levels, the relevance of this mechanism to normal metabolism or to the MCD phenotype is not known. In this study, we show that mRNA levels of enzymes involved in biotin utilization, including HCS, are down-regulated during biotin deficiency in liver while remaining constitutively expressed in brain. We propose that this mechanism of regulation is aimed at sparing the essential function of biotin in the brain at the expense of organs such as liver and kidney during biotin deprivation. In MCD, it is possible that some of the manifestations of the disease may be associated with down-regulation of biotin utilization in liver because of the impaired activity of HCS and that high dose biotin therapy may in part be important to overcoming the adverse regulatory impact in such organs.

Advances in the Biology and Genetics of the Podocytopathies: Implications for Diagnosis and Therapy

2009 ◽  
Vol 133 (2) ◽  
pp. 201-216 ◽  
Author(s):  
Laura Barisoni ◽  
H. William Schnaper ◽  
Jeffrey B. Kopp
Keyword(s):  
Current Knowledge ◽  
Diffuse Mesangial Sclerosis ◽  
Therapeutic Approaches ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Collapsing Glomerulopathy ◽  
Novel Approach ◽  
Genes Encoding ◽  
Glomerular Morphology

AbstractContext.—Etiologic factors and pathways leading to altered podocyte phenotype are clearly numerous and involve the activity of different cellular function.Objective.—To focus on recent discoveries in podocyte biology and genetics and their relevance to these human glomerular diseases, named podocytopathies.Data Sources.—Genetic mutations in genes encoding for proteins in the nucleus, slit diaphragm, podocyte cytoplasm, and cell membrane are responsible for podocyte phenotype and functional abnormalities. Podocyte injury may also derive from secondary stimuli, such as mechanical stress, infections, or use of certain medications. Podocytes can respond to injury in a limited number of ways, which include (1) effacement, (2) apoptosis, (3) arrest of development, and (4) dedifferentiation. Each of these pathways results in a specific glomerular morphology: minimal change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy.Conclusions.—Based on current knowledge of podocyte biology, we organized etiologic factors and morphologic features in a taxonomy of podocytopathies, which provides a novel approach to the classification of these diseases. Current and experimental therapeutic approaches are also discussed.

Effect of gallic acid on the reproduction of adolescent male Brandt’s vole (Lasiopodomys brandtii)

2021 ◽  
Author(s):  
Xin Dai ◽  
Xiao-Feng Sun ◽  
Ai-Qin Wang ◽  
Wanhong Wei ◽  
Sheng-Mei Yang
Keyword(s):  
Gallic Acid ◽  
Low Dose ◽  
Regulatory Protein ◽  
Antioxidant Properties ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Lasiopodomys Brandtii

Gallic acid (GA), a phenol that is present in various plants, potentially contains antioxidant properties. This study aimed to investigate the effects of GA on the reproduction of adolescent male Brandt’s voles (Lasiopodomys brandtii (Radde, 1861)). Antioxidant levels and apoptosis in the testis, as well as reproductive physiology, were evaluated in adolescent males treated with GA. The results showed that a low dose of GA enhanced relative epididymis weight and the sperm density in the epididymis, increased the mRNA levels of steroidogenic acute regulatory protein in the testis, and reduced the percentages of abnormal and dead sperm. In addition, a low dose of GA significantly increased the levels of superoxide dismutase, catalase, and glutathione peroxidase, and decreased the level of malondialdehyde in the testis, as well as the mRNA and protein levels of the apoptosis related gene, caspase-3. However, a high dose of GA sharply reduced the average diameter of the seminiferous tubules compared to a low dose. Collectively, these findings demonstrate that GA treatment during puberty affects the reproductive responses of male Brandt’s voles in a dose-dependent manner by regulating antioxidant levels and apoptosis.

Metabolism is not a Major Contributor to the Toxicity of Piperaquine, a Major Partner Antimalarial in Artemisinin-Based Combination Therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Liyuan Zhang ◽  
Zhaohua Liu ◽  
Yunrui Zhang ◽  
Yuewu Xie ◽  
Jie Xing
Keyword(s):  
Histopathological Examination ◽  
High Dose ◽  
Mrna Levels ◽  
Apoptosis Pathway ◽  
Hepatocellular Damage ◽  
Serum Biochemical ◽  
Oral Doses ◽  
Dose Dependent ◽  
Cumulative Exposures

Background: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. Objectives: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. Method: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. Results: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. Conclusions: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.

scholarly journals Divergent effects of low versus high dose anti-TGF-β antibody in puromycin aminonucleoside nephropathy in rats

2004 ◽  
Vol 65 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Li.-Jun. Ma ◽  
Sharda Jha ◽  
Hong Ling ◽  
Ambra Pozzi ◽  
Steve Ledbetter ◽  
...  
Keyword(s):  
High Dose ◽  
Puromycin Aminonucleoside

scholarly journals Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria

2019 ◽  
Vol 317 (1) ◽  
pp. F12-F22 ◽  
Author(s):  
Li-Hong Zhang ◽  
Xiang-Yang Zhu ◽  
Alfonso Eirin ◽  
Arash Aghajani Nargesi ◽  
John R. Woollard ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Vesicles ◽  
Light And Electron Microscopy ◽  
Urinary Concentration ◽  
Glomerular Injury ◽  
Podocyte Injury ◽  
Early Markers ◽  
Nutrient Surplus ◽  
Glomerular Size ◽  
Foot Process

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg−1·day−1 sc) for the last month of diet, and lean controls ( n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

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