A new recombinant MnSOD prevents the Cyclosporine A-induced renal impairment

Damiano, Sara; Trepiccione, Francesco; Ciarcia, Roberto; Scanni, Roberto; Spagnuolo, Manuela; Manco, L.; Borrelli, Antonella; Capasso, Clemente; Mancini, R. E.; Schiattarella, Antonella; Iervolino, Anna; Zacchia, Enza; Bata-Csere, Andrea; Florio, Salvatore; Anastasio, P; Pollastro, Rosa Maria; Mancini, Aldo; Capasso, Giovambattista

doi:10.1093/ndt/gft020

Cited by 25 publications

(33 citation statements)

References 22 publications

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“… 49 , 50 Previous studies established that ROS production and oxidative stress are involved in CsA nephrotoxicity. 35 , 46 , 51 This study supported our hypothesis that SCE had renal protective effects in CsA nephrotoxicity model, a well-established renal injury model. In this model, CsA-induced generation of ROS led to an increase in the expression of 4-HNE (a product of lipid peroxidation) and HO-1 (an inducible isoform in response to oxidative stress).…”

Section: Discussionsupporting

confidence: 84%

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Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Lai¹,

Wei²,

Mahmoodurrahman³

et al. 2015

DDDT

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Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of CsA-induced side effects in the People’s Republic of China. This study aimed to investigate the possible effects of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the development of CsA-induced nephrotoxicity. A liquid chromatography/tandem mass spectrometry method was developed and validated for determining the effect of SCE on the pharmacokinetics of CsA. Male Sprague Dawley rats, which were administered with CsA (25 mg/kg/d) alone or in combination with SCE (54 mg/kg/d and 108 mg/kg/d) for 28 days, were used to evaluate the nephroprotective effects of SCE. Our study showed that SCE increased the mean blood concentration of CsA. Furthermore, we found that the concomitant administration of SCE alongside CsA prevented the disruption of catalase activity and reduction in creatinine, urea, renal malondialdehyde, and glutathione peroxidase levels that would have otherwise occurred in the absence of SCE administration. SCE treatment markedly suppressed the expression of 4-hydroxynonenal, Bcl-2-associated X protein, cleaved caspase 3, and autophagy-related protein LC3 A/B. On the other hand, the expression of heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf2), and P-glycoprotein was enhanced by the very same addition of SCE. SCE was also able to increase the systemic exposure of CsA in rats. The renoprotective effects of SCE were thought to be mediated by its antiapoptotic and antioxidant abilities, which caused the attenuation of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an effective adjunct in a CsA-based immunosuppressive regimen.

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Section: Discussionsupporting

confidence: 84%

“…Numerous studies have demonstrated that the CsA-induced nephrotoxicity, which is characterized by decreased glomerular filtration rate and fibrosis, is a major cause of chronic renal disease in rat models and this can be applied to clinical practice as well. 35 …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Lai¹,

Wei²,

Mahmoodurrahman³

et al. 2015

DDDT

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“…Inulin clearance was performed as previously described [ 18 ]. Briefly, mice were anesthetized with Inactin (Sigma) 100 mg/kgBW, tracheostomized, placed on a surgical table.…”

Section: Methodsmentioning

confidence: 99%

Selective Dicer Suppression in the Kidney Alters GSK3β/β-Catenin Pathways Promoting a Glomerulocystic Disease

et al. 2015

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Dicer is a crucial enzyme for the maturation of miRNAs. Mutations in the Dicer gene are highly associated with Pleuro Pulmonary Blastoma-Family Dysplasia Syndrome (PPB-FDS, OMIM 601200), recently proposed to be renamed Dicer syndrome. Aside from the pulmonary phenotype (blastoma), renal nephroma and thyroid goiter are frequently part of Dicer syndrome. To investigate the renal phenotype, conditional knockout (cKO) mice for Dicer in Pax8 expressing cells were generated. Dicer cKO mice progressively develop a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria and severe renal failure. Higher cellular turnover of the parietal cells of Bowman’s capsule precedes the development of the cysts and the primary cilium progressively disappears with cyst-enlargement. Upregulation of GSK3β precedes the development of the glomerulocystic phenotype. Downregulation of β-catenin in the renal cortex and its cytosolic removal in the cells lining the cysts may be associated with observed accumulation of GSK3β. Alterations of β-catenin regulating pathways could promote cystic degeneration as in other models. Thus, miRNAs are fundamental in preserving renal morphology and function. Alteration of the GSK3β/β-catenin pathway could be a crucial mechanism linking miRNA dysregulation and the development of a glomerulocystic disease.

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“…mesangial function) contributions [ 31 , 32 ]. Several factors, such as reactive oxygen species, may functionally modulate the GFR [ 33 ]. The data on urinary volume and urinary sodium are in keeping with the well-known effects of AVP on diuresis and urinary sodium excretion, as well as with the data from four patients with CDI studied by Hanouna et al .…”

Section: Discussionmentioning

confidence: 99%

Regulation of urinary calcium excretion by vasopressin

Anastasio

Trepiccione

Santo

et al. 2020

Clinical Kidney Journal

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Background The antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates the body's water balance. Recently, modifications in AVP levels have been related to osteoporosis during ageing and microgravity/bed rest. Therefore the present study was devised to assess whether the absence of AVP, as in patients with central diabetes insipidus (CDI), modulates renal calcium excretion. Methods We retrospectively analysed data from 12 patients with CDI with measured 24-h urinary excretion levels of calcium. Data were available at the moment of the diagnosis when patients were drug-free and after therapy with dDAVP, an analog of AVP. Hypercalciuria was defined as 24-h urinary Ca2+ >275 mg/day in males and >250 mg/day in females and a urinary calcium (Ca):creatinine (Cr) ratio >0.20 mg/mg. Results Untreated CDI patients had a daily urinary Ca2+ excretion of 383 ± 47 mg/day and a urinary Ca:Cr ratio of 0.26 ± 0.38 mg/mg. The urine osmolarity significantly increased after the administration of dDAVP by 210% and the urinary flow decreased by 72%. Furthermore, the estimated glomerular filtration rate (eGFR) increased by 7%, which did not reach statistical significance. dDAVP treatment did not significantly modify the urinary Ca2+ concentration; however, the daily calcium excretion and the urinary Ca:Cr ratio were significantly decreased (160 ± 27 mg/day and 0.11 ± 0.02 mg/mg, respectively). Conclusions Patients with CDI show hypercalciuria even though urine is more diluted than normal controls, and dDAVP reverses this effect. These data support the intriguing relationship between AVP and osteoporosis in ageing and microgravity/bed rest.

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A new recombinant MnSOD prevents the Cyclosporine A-induced renal impairment

Abstract: Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS.

Cited by 25 publications

References 22 publications

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Selective Dicer Suppression in the Kidney Alters GSK3β/β-Catenin Pathways Promoting a Glomerulocystic Disease

Regulation of urinary calcium excretion by vasopressin

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