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      Protective effect of calcitriol on rhabdomyolysis-induced acute kidney injury in rats

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          Abstract

          Glycerol injection in rats can lead to rhabdomyolysis, with the release of the intracellular muscle content to the extracellular compartment and acute kidney injury (AKI). Oxidative stress and the inflammatory processes contribute to the disturbances in renal function and structure observed in this model. This study evaluated the effect of calcitriol administration in AKI induced by rhabdomyolysis and its relationship with oxidative damage and inflammatory process. Male Wistar Hannover rats were treated with calcitriol (6 ng/day) or vehicle (0.9% NaCl) for 7 days and were injected with 50% glycerol or saline 3 days after the beginning of calcitriol or saline administration. Four days after glycerol or saline injection, urine, plasma and renal tissue samples were collected for renal function and structural analysis. The oxidative stress and the inflammatory processes were also evaluated. Glycerol-injected rats presented increased sodium fractional excretion and decreased glomerular filtration rates. These alterations were associated with tubular injury in the renal cortex. These animals also presented increased oxidative damage, apoptosis, inflammation, higher urinary excretion of vitamin D-binding protein and decreased cubilin expression in renal tissue. All these alterations were less intense in calcitriol-treated animals. This effect was associated with decreases in oxidative damage and inflammation.

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          Most cited references29

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          Rhabdomyolysis: a review of the literature.

          F Y Khan (2009)
          Rhabdomyolysis is a potentially life-threatening syndrome that can develop from a variety of causes; the classic findings of muscular aches, weakness and tea-coloured urine are non-specific and may not always be present. The diagnosis therefore rests upon the presence of a high level of suspicion of any abnormal laboratory values in the mind of the treating physician. An elevated plasma creatine kinase (CK) level is the most sensitive laboratory finding pertaining to muscle injury; whereas hyperkalaemia, acute renal failure and compartment syndrome represent the major life-threatening complications. The management of the condition includes prompt and aggressive fluid resuscitation, elimination of the causative agents and treatment and prevention of any complications that may ensue. The objective of this review is to describe the aetiological spectrum and pathophysiology of rhabdomyolysis, the clinical and biological consequences of this syndrome and to provide an appraisal of the current data available in order to facilitate the prevention, early diagnosis and prompt management of this condition.
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            Rhabdomyolysis.

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              Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat.

              Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinate amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomyolysis.
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                Author and article information

                Contributors
                tmcoimbr@fmrp.usp.br
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 May 2019
                8 May 2019
                2019
                : 9
                : 7090
                Affiliations
                [1 ]ISNI 0000 0004 1937 0722, GRID grid.11899.38, Departments of Physiology, , University of São Paulo, ; Ribeirão Preto, São Paulo Brazil
                [2 ]ISNI 0000 0004 1937 0722, GRID grid.11899.38, Departments of Pathology of Ribeirão Preto Medical School, , University of São Paulo, ; Ribeirão Preto, São Paulo Brazil
                Article
                43564
                10.1038/s41598-019-43564-1
                6506495
                31068635
                cec71460-d114-4a7f-9d53-4a0d5e5b9344
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 September 2018
                : 27 April 2019
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                © The Author(s) 2019

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                physiology,nephrons
                Uncategorized
                physiology, nephrons

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