Dual Effects of Lisinopril on Puromycin Aminonucleoside Nephrosis in Unilaterally Nephrectomized Rats.

Shinosaki, Toshihiro; Takagawa, Ikuko; Sunagawa, Norio; Yonetani, Yukio; Kurihara, Hidetake

doi:10.1254/jjp.73.337

Cited by 4 publications

(3 citation statements)

References 19 publications

(11 reference statements)

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“…Our impression is that the pathomechanisms involved in early PAN may be beyond the reach of being significantly affected by ACE inhibitors. Earlier studies show variable results [36,37,38,39]. Recent studies separating the two types of angiotensin receptors have suggested that they have opposite actions [40].…”

Section: Discussionmentioning

confidence: 99%

Permeability, Ultrastructural Changes, and Distribution of Novel Proteins in the Glomerular Barrier in Early Puromycin Aminonucleoside Nephrosis

Dunér¹,

Lindström²,

Hultenby³

et al. 2010

Nephron Exp Nephrol

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Background/Aims: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. Methods: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. Results: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. Conclusions: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas α-actinin was unchanged.

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Section: Discussionmentioning

confidence: 99%

Permeability, Ultrastructural Changes, and Distribution of Novel Proteins in the Glomerular Barrier in Early Puromycin Aminonucleoside Nephrosis

Dunér¹,

Lindström²,

Hultenby³

et al. 2010

Nephron Exp Nephrol

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“…Lisinopril 20 mg/kg has anti-hypertensive effect in previous pre-clinical studies, whereas lisinopril 50 mg/kg reduced urinary protein excretion, indicating therapeutic action of lisinopril against proteinuria. [151617] Rosuvastatin 40 mg/kg showed anti-hyperlipidemic effect in previous studies, whereas higher dose (≥80 mg/kg) of rosuvastatin induced myopathy in rats. [1819]…”

Section: Methodsmentioning

confidence: 99%

Evaluation of adverse effects of lisinopril and rosuvastatin on hematological and biochemical analytes in wistar rats

Dodiya¹,

Kale²,

Goswami³

et al. 2013

Toxicol Int

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Objective:Combination therapy of lisinopril and rosuvastatin may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders. The present study was designed to evaluate toxic effects of lisinopril and rosuvastatin alone or its combination therapy on hematological and biochemical analytes in Wistar rats.Materials and Methods:Forty-two rats were divided into seven groups, with each group comprising six rats. Rats were administered with lisinopril, rosuvastatin alone, or in-combination at two different doses. The blood samples were collected from rats after 21 days of oral administration of the drug/s and analyzed for various hematological and biochemical analytes.Results:Lisinopril alone and its combination treatment with rosuvastatin at high doses decreased hemoglobin and hematocrit. Rosuvastatin alone at high dose and its concomitant administration with lisinopril at two different doses showed increase in total white blood cells and absolute lymphocyte count and neutrophil count. Serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin were significantly increased in rosuvastatin alone and its combination with lisinopril at both the doses. Besides this, lisinopril treatment decreased serum levels of sodium and increased the levels of potassium. Serum creatine kinase (CK) levels were increased in the animals treated with rosuvastatin at both the doses. However, increased serum CK level because of rosuvastatin became normal with co-administration of lisinopril at low doses.Conclusion:Our results indicate that administration of lisinopril with rosuvastatin does not ameliorate hepatotoxicity caused by rosuvastatin. However, combination treatment reduces serum CK levels elevated due to rosuvastatin, implicating protective effect of combination treatment on myopathy at low doses.

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“…The detection of ACSs on the GBM was performed as previously reported [29]. The kidney was cut into small pieces and immersed in a mixture of 0.1% glutaraldehyde and 2% phosphotungstic acid.…”

Section: Methodsmentioning

confidence: 99%

Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis

Kuroda¹,

Masui²,

Notoya³

et al. 2012

Nephron Extra

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Background/Aim: Matrix metalloproteinases (MMPs) play pivotal roles in extracellular matrix turnover and are involved in chronic kidney disease. The renoprotective action of a synthetic MMP inhibitor, compound A, was investigated in chronic nephritis. Methods: Nephritis was induced by a single injection of anti-Thy1.1 antibody to unilaterally nephrectomized rats. The effects of compound A on proteinuria, blood urea nitrogen, and matrix-related gene expressions were evaluated. Collagen accumulation, as assessed by periodic acid-Schiff staining and hydroxyproline content, was determined. The integrity of glomerular epithelial cells and glomerular basement membrane was evaluated with desmin immunohistochemistry and electron microscopic detection of anionic charge sites, respectively. Results: Treatment with compound A notably attenuated proteinuria, ameliorated blood urea nitrogen, and prevented glomerulosclerosis. Gene upregulation of collagen and transforming growth factor β1 in the cortex was prevented in the treated animals. Glomerular epithelial cell injury was milder, and glomerular basement membrane anionic sites were protected with the treatment. Conclusion: A novel MMP inhibitor, compound A, exerts protective effects in progressive glomerulonephritis. Compound A ameliorates various aspects of renal injuries and may have therapeutic potential toward kidney diseases.

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Dual Effects of Lisinopril on Puromycin Aminonucleoside Nephrosis in Unilaterally Nephrectomized Rats.

Cited by 4 publications

References 19 publications

Permeability, Ultrastructural Changes, and Distribution of Novel Proteins in the Glomerular Barrier in Early Puromycin Aminonucleoside Nephrosis

Permeability, Ultrastructural Changes, and Distribution of Novel Proteins in the Glomerular Barrier in Early Puromycin Aminonucleoside Nephrosis

Evaluation of adverse effects of lisinopril and rosuvastatin on hematological and biochemical analytes in wistar rats

Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis

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