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Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats
The heme component of myoglobin plays a crucial role in the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI). Heme oxiganenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism, and its metabolites, iron, biliverdin, and carbon monoxide, have antioxidant properties. Tin c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926186/ https://www.ncbi.nlm.nih.gov/pubmed/35294485 http://dx.doi.org/10.1371/journal.pone.0265512 |
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author | Ohtani, Shinkichi Shimizu, Hiroko Yamaoka, Masakazu Takahashi, Toru Omori, Emiko Morimatsu, Hiroshi |
author_facet | Ohtani, Shinkichi Shimizu, Hiroko Yamaoka, Masakazu Takahashi, Toru Omori, Emiko Morimatsu, Hiroshi |
author_sort | Ohtani, Shinkichi |
collection | PubMed |
description | The heme component of myoglobin plays a crucial role in the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI). Heme oxiganenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism, and its metabolites, iron, biliverdin, and carbon monoxide, have antioxidant properties. Tin chloride (SnCl(2)) is a kidney specific HO-1 inducer. In this study, we examined whether the induction of HO-1 in the kidney by SnCl(₂) pretreatment ameliorates RM-AKI in rats and if the effect is due to the degradation of excess renal free heme. We developed an RM-AKI rat (male Sprague-Dawley rats) model by injecting glycerol (Gly) in the hind limbs. RM-AKI rats were pretreated with saline or SnCl(₂) or additional SnMP (tin mesoporphyrin, a specific HO inhibitor) followed by Gly treatment. Serum blood urea nitrogen (BUN) and creatinine (Crea) were measured as indicators of renal function. Renal free heme level was assessed based on the levels of δ-aminolevulinate synthase (ALAS1), a heme biosynthetic enzyme, and nuclear BTB and CNC homology 1 (Bach1), an inhibitory transcription factor of HO-1. Elevated free heme levels lead to decreases in ALAS1 and nuclear Bach1. After 24 h of Gly injection, serum BUN and Crea levels in saline-pretreated rats were significantly higher than those in untreated control rats. In contrast, SnCl(₂)-pretreated rats showed no significant increase in the indices. However, additional treatment of SnMP abolished the beneficial effect of SnCl(₂). Renal ALAS1 mRNA levels and renal nuclear Bach1 protein levels in the saline pretreated rats were significantly lower than those in control rats 3 h after Gly injection. In contrast, the levels in SnCl₂-pretreated rats were not altered. The findings indicate that SnCl(2) pretreatment confers protection against RM-AKI by virtue of HO-1 induction in the renal system, at least in part through excess free heme degradation. |
format | Online Article Text |
id | pubmed-8926186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89261862022-03-17 Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats Ohtani, Shinkichi Shimizu, Hiroko Yamaoka, Masakazu Takahashi, Toru Omori, Emiko Morimatsu, Hiroshi PLoS One Research Article The heme component of myoglobin plays a crucial role in the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI). Heme oxiganenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism, and its metabolites, iron, biliverdin, and carbon monoxide, have antioxidant properties. Tin chloride (SnCl(2)) is a kidney specific HO-1 inducer. In this study, we examined whether the induction of HO-1 in the kidney by SnCl(₂) pretreatment ameliorates RM-AKI in rats and if the effect is due to the degradation of excess renal free heme. We developed an RM-AKI rat (male Sprague-Dawley rats) model by injecting glycerol (Gly) in the hind limbs. RM-AKI rats were pretreated with saline or SnCl(₂) or additional SnMP (tin mesoporphyrin, a specific HO inhibitor) followed by Gly treatment. Serum blood urea nitrogen (BUN) and creatinine (Crea) were measured as indicators of renal function. Renal free heme level was assessed based on the levels of δ-aminolevulinate synthase (ALAS1), a heme biosynthetic enzyme, and nuclear BTB and CNC homology 1 (Bach1), an inhibitory transcription factor of HO-1. Elevated free heme levels lead to decreases in ALAS1 and nuclear Bach1. After 24 h of Gly injection, serum BUN and Crea levels in saline-pretreated rats were significantly higher than those in untreated control rats. In contrast, SnCl(₂)-pretreated rats showed no significant increase in the indices. However, additional treatment of SnMP abolished the beneficial effect of SnCl(₂). Renal ALAS1 mRNA levels and renal nuclear Bach1 protein levels in the saline pretreated rats were significantly lower than those in control rats 3 h after Gly injection. In contrast, the levels in SnCl₂-pretreated rats were not altered. The findings indicate that SnCl(2) pretreatment confers protection against RM-AKI by virtue of HO-1 induction in the renal system, at least in part through excess free heme degradation. Public Library of Science 2022-03-16 /pmc/articles/PMC8926186/ /pubmed/35294485 http://dx.doi.org/10.1371/journal.pone.0265512 Text en © 2022 Ohtani et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ohtani, Shinkichi Shimizu, Hiroko Yamaoka, Masakazu Takahashi, Toru Omori, Emiko Morimatsu, Hiroshi Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title | Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title_full | Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title_fullStr | Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title_full_unstemmed | Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title_short | Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
title_sort | protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926186/ https://www.ncbi.nlm.nih.gov/pubmed/35294485 http://dx.doi.org/10.1371/journal.pone.0265512 |
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