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Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats
Doxorubicin (DOX) is a highly effective chemotherapy agent prescribed for cancer treatment. However, the clinical use of DOX is limited due to off-target toxicity in healthy tissues. In this regard, hepatic and renal metabolic clearance results in DOX accumulation within these organ systems. Within...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298992/ https://www.ncbi.nlm.nih.gov/pubmed/37373368 http://dx.doi.org/10.3390/ijms241210222 |
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author | Boeno, Franccesco P. Patel, Jay Montalvo, Ryan N. Lapierre-Nguyen, Stephanie S. Schreiber, Claire M. Smuder, Ashley J. |
author_facet | Boeno, Franccesco P. Patel, Jay Montalvo, Ryan N. Lapierre-Nguyen, Stephanie S. Schreiber, Claire M. Smuder, Ashley J. |
author_sort | Boeno, Franccesco P. |
collection | PubMed |
description | Doxorubicin (DOX) is a highly effective chemotherapy agent prescribed for cancer treatment. However, the clinical use of DOX is limited due to off-target toxicity in healthy tissues. In this regard, hepatic and renal metabolic clearance results in DOX accumulation within these organ systems. Within the liver and kidneys, DOX causes inflammation and oxidative stress, which promotes cytotoxic cellular signaling. While there is currently no standard of care to treat DOX hepatic- and nephrotoxicity, endurance exercise preconditioning may be an effective intervention to prevent elevations in liver alanine transaminase (ALT) and aspartate aminotransferase (AST) and to improve kidney creatinine clearance. To determine whether exercise preconditioning is sufficient to reduce liver and kidney toxicity resulting from acute exposure to DOX chemotherapy treatment, male and female Sprague–Dawley rats remained sedentary or were exercise trained prior to saline or DOX exposure. Our findings demonstrate that DOX treatment elevated AST and AST/ALT in male rats, with no effects of exercise preconditioning to prevent these increases. We also showed increased plasma markers of renin–angiotensin–aldosterone system (RAAS) activation and urine markers of proteinuria and proximal tubule damage, with male rats revealing greater differences compared to females. Exercise preconditioning showed improved urine creatinine clearance and reduced cystatin c in males, while females had reduced plasma angiotensin II (AngII) levels. Our results demonstrate both tissue- and sex-specific responses related to the effects of exercise preconditioning and DOX treatment on markers of liver and kidney toxicity. |
format | Online Article Text |
id | pubmed-10298992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102989922023-06-28 Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats Boeno, Franccesco P. Patel, Jay Montalvo, Ryan N. Lapierre-Nguyen, Stephanie S. Schreiber, Claire M. Smuder, Ashley J. Int J Mol Sci Article Doxorubicin (DOX) is a highly effective chemotherapy agent prescribed for cancer treatment. However, the clinical use of DOX is limited due to off-target toxicity in healthy tissues. In this regard, hepatic and renal metabolic clearance results in DOX accumulation within these organ systems. Within the liver and kidneys, DOX causes inflammation and oxidative stress, which promotes cytotoxic cellular signaling. While there is currently no standard of care to treat DOX hepatic- and nephrotoxicity, endurance exercise preconditioning may be an effective intervention to prevent elevations in liver alanine transaminase (ALT) and aspartate aminotransferase (AST) and to improve kidney creatinine clearance. To determine whether exercise preconditioning is sufficient to reduce liver and kidney toxicity resulting from acute exposure to DOX chemotherapy treatment, male and female Sprague–Dawley rats remained sedentary or were exercise trained prior to saline or DOX exposure. Our findings demonstrate that DOX treatment elevated AST and AST/ALT in male rats, with no effects of exercise preconditioning to prevent these increases. We also showed increased plasma markers of renin–angiotensin–aldosterone system (RAAS) activation and urine markers of proteinuria and proximal tubule damage, with male rats revealing greater differences compared to females. Exercise preconditioning showed improved urine creatinine clearance and reduced cystatin c in males, while females had reduced plasma angiotensin II (AngII) levels. Our results demonstrate both tissue- and sex-specific responses related to the effects of exercise preconditioning and DOX treatment on markers of liver and kidney toxicity. MDPI 2023-06-16 /pmc/articles/PMC10298992/ /pubmed/37373368 http://dx.doi.org/10.3390/ijms241210222 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Boeno, Franccesco P. Patel, Jay Montalvo, Ryan N. Lapierre-Nguyen, Stephanie S. Schreiber, Claire M. Smuder, Ashley J. Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title | Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title_full | Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title_fullStr | Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title_full_unstemmed | Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title_short | Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats |
title_sort | effects of exercise preconditioning on doxorubicin-induced liver and kidney toxicity in male and female rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298992/ https://www.ncbi.nlm.nih.gov/pubmed/37373368 http://dx.doi.org/10.3390/ijms241210222 |
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