21 September 2018 : Animal Research
Med Sci Monit 2018; 24: ANS6666-6672
BACKGROUND: Patients treated with 5-FU can develop rare but potentially severe cardiac effects, including cardiomyopathy, angina pectoris, ventricular tachycardia, heart failure, acute myocardial infarction, and cardiogenic shock. The specific pathologies and mechanisms are not fully understood. Research found that mitochondrial dynamics are widely detected in many angiocardiopathies. Therefore, in the present study we studied the mitochondrial damage and explored the role of mitochondrial fusion/fission proteins on myocardium of rats treated with 5-fluorouracil (5-FU).
MATERIAL AND METHODS: Thirty male SD rats were randomly divided into 3 groups with 10 rats in each group: (1) control group, (2) low 5-FU group (25 mg/kg), (3) high 5-FU group (50 mg/kg). The animals received intraperitoneal injection for 5 consecutive days. We assessed alterations in mitochondrial morphology, ATP content, mitochondrial membrane potential, and mitochondria fusion/fission proteins expression in hearts of rats receiving intraperitoneal injection with different doses of 5-FU.
RESULTS: 5-FU intraperitoneal injection induced ultra-structural damage in hearts, such as mitochondrial swelling, cristae disorder, and vacuolization. These changes were accompanied by decreases of mitochondrial membrane potential. The low dose of 5-FU led to a slight increase in ATP content. However, the high 5-FU dose caused a more significant reduction compared with the control group. Furthermore, 5-FU intraperitoneal injection significantly increased specific mitochondrial fission proteins (Drp1 and Fis1) and decreased mitochondrial fusion proteins (Opa1, Mfn1, and Mfn2) in rat hearts. However, no changes in cardiac structure and function were detected by echocardiogram. The high dose caused more damage to mitochondrial function than the low dose.
CONCLUSIONS: Mitochondrial damage is a potentially important mechanism and early indicator for 5-FU-induced cardiovascular disease.
Keywords: Fluorouracil, Mitochondrial Dynamics, Membrane Potential, Mitochondrial
01 February 2023 : EditorialEditorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread
Med Sci Monit 2023; 29:e939580
19 January 2023 : Clinical ResearchEvaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...
Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical ResearchDetermining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...
Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical ResearchEffect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...
Med Sci Monit 2022; 28:e938926
03 Feb 2023 : Clinical ResearchTreatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and L...
Med Sci Monit In Press; DOI: 10.12659/MSM.938865
02 Feb 2023 : Clinical ResearchOnline Questionnaire-Based Study to Evaluate the Attitudes and Use of Rubber Dental Dams by Saudi Dental Pr...
Med Sci Monit In Press; DOI: 10.12659/MSM.938672
02 Feb 2023 : Database AnalysisPrognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based...
Med Sci Monit In Press; DOI: 10.12659/MSM.938785
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292