Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats
Introduction: FOLFOX chemotherapy (CTx) is used for the treatment of colorectal liver metastasis (CRLM). Side effects include rare cardiotoxicity, which may limit the application of FOLFOX. Currently, there is no effective strategy to prevent FOLFOX-induced cardiotoxicity. Glycine has been shown to...
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MDPI AG
2020-08-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/9/2634 |
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| author | Juste Maneikyte Augustinas Bausys Bettina Leber Nicole Feldbacher Gerald Hoefler Dagmar Kolb-Lenz Kestutis Strupas Philipp Stiegler Peter Schemmer |
| author_facet | Juste Maneikyte Augustinas Bausys Bettina Leber Nicole Feldbacher Gerald Hoefler Dagmar Kolb-Lenz Kestutis Strupas Philipp Stiegler Peter Schemmer |
| author_sort | Juste Maneikyte |
| collection | DOAJ |
| description | Introduction: FOLFOX chemotherapy (CTx) is used for the treatment of colorectal liver metastasis (CRLM). Side effects include rare cardiotoxicity, which may limit the application of FOLFOX. Currently, there is no effective strategy to prevent FOLFOX-induced cardiotoxicity. Glycine has been shown to protect livers from CTx-induced injury and oxidative stress, and it reduces platelet aggregation and improves microperfusion. This study tested the hypothesis of glycine being cardioprotective in a rat model of FOLFOX in combination with CRLM. Materials and Methods: The effect of glycine was tested in vitro on human cardiac myocytes (HCMs). To test glycine in vivo Wag/Rij rats with induced CRLM were treated with FOLFOX ±5% dietary glycine. Left ventricle ejection fraction (LVEF), myocardial fibrosis, and apoptosis, also heart fatty acid binding protein (h-FABP) and brain natriuretic peptide levels were monitored. PCR analysis for Collagen type I, II, and brain natriuretic peptide (BNP) in the heart muscle was performed. Results: In vitro glycine had no effect on HCM cell viability. Treatment with FOLFOX resulted in a significant increase of h-FABP levels, increased myocardial fibrosis, and apoptosis as well as increased expression of type I Collagen. Furthermore, FOLFOX caused a decrease of LVEF by 10% (<i>p</i> = 0.028). Dietary glycine prevented FOLFOX-induced myocardial injury by preserving the LVEF and reducing the levels of fibrosis (<i>p</i> = 0.012) and apoptosis (<i>p</i> = 0.015) in vivo. Conclusions: Data presented here demonstrate for the first time that dietary glycine protects the heart against FOLFOX-induced injury during treatment for CRLM. |
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| language | English |
| last_indexed | 2024-03-10T16:44:06Z |
| publishDate | 2020-08-01 |
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| series | Nutrients |
| spelling | doaj.art-a8fcf390ea7d48f7b3cdb1b8653ab7e62023-11-20T11:47:27ZengMDPI AGNutrients2072-66432020-08-01129263410.3390/nu12092634Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in RatsJuste Maneikyte0Augustinas Bausys1Bettina Leber2Nicole Feldbacher3Gerald Hoefler4Dagmar Kolb-Lenz5Kestutis Strupas6Philipp Stiegler7Peter Schemmer8General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaGeneral, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaGeneral, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaGeneral, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, AustriaInstitute of Cell Biology, Histology and Embryology, Medical University Graz, 8010 Graz, AustriaFaculty of Medicine, Vilnius University, 03101 Vilnius, LithuaniaGeneral, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaGeneral, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, AustriaIntroduction: FOLFOX chemotherapy (CTx) is used for the treatment of colorectal liver metastasis (CRLM). Side effects include rare cardiotoxicity, which may limit the application of FOLFOX. Currently, there is no effective strategy to prevent FOLFOX-induced cardiotoxicity. Glycine has been shown to protect livers from CTx-induced injury and oxidative stress, and it reduces platelet aggregation and improves microperfusion. This study tested the hypothesis of glycine being cardioprotective in a rat model of FOLFOX in combination with CRLM. Materials and Methods: The effect of glycine was tested in vitro on human cardiac myocytes (HCMs). To test glycine in vivo Wag/Rij rats with induced CRLM were treated with FOLFOX ±5% dietary glycine. Left ventricle ejection fraction (LVEF), myocardial fibrosis, and apoptosis, also heart fatty acid binding protein (h-FABP) and brain natriuretic peptide levels were monitored. PCR analysis for Collagen type I, II, and brain natriuretic peptide (BNP) in the heart muscle was performed. Results: In vitro glycine had no effect on HCM cell viability. Treatment with FOLFOX resulted in a significant increase of h-FABP levels, increased myocardial fibrosis, and apoptosis as well as increased expression of type I Collagen. Furthermore, FOLFOX caused a decrease of LVEF by 10% (<i>p</i> = 0.028). Dietary glycine prevented FOLFOX-induced myocardial injury by preserving the LVEF and reducing the levels of fibrosis (<i>p</i> = 0.012) and apoptosis (<i>p</i> = 0.015) in vivo. Conclusions: Data presented here demonstrate for the first time that dietary glycine protects the heart against FOLFOX-induced injury during treatment for CRLM.https://www.mdpi.com/2072-6643/12/9/2634glycineFOLFOXcardiotoxicitycolorectal cancer |
| spellingShingle | Juste Maneikyte Augustinas Bausys Bettina Leber Nicole Feldbacher Gerald Hoefler Dagmar Kolb-Lenz Kestutis Strupas Philipp Stiegler Peter Schemmer Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats Nutrients glycine FOLFOX cardiotoxicity colorectal cancer |
| title | Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats |
| title_full | Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats |
| title_fullStr | Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats |
| title_full_unstemmed | Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats |
| title_short | Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats |
| title_sort | dietary glycine prevents folfox chemotherapy induced heart injury a colorectal cancer liver metastasis treatment model in rats |
| topic | glycine FOLFOX cardiotoxicity colorectal cancer |
| url | https://www.mdpi.com/2072-6643/12/9/2634 |
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