Key result
5-Fluorouracil induced ultra-structural mitochondrial damage in rat hearts, decreased mitochondrial membrane potential, increased fission proteins, and decreased fusion proteins.
Why the study?
Does 5-fluorouracil induce mitochondrial damage and alter mitochondrial fusion/fission proteins in rat hearts?
Does 5-fluorouracil induce mitochondrial damage and alter mitochondrial fusion/fission proteins in rat hearts?
5-fluorouracil induces mitochondrial damage in rat hearts by disrupting the balance of mitochondrial fusion and fission proteins, providing a potential mechanism for its cardiotoxic effects.
Hypothesis-generating for mitochondrial dysfunction as a mechanism of 5-FU cardiotoxicity;.
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.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2018) studied 5-FU-induced cardiotoxicity (n=30). 5-fluorouracil vs. Control (physiological saline) was evaluated on Mitochondrial morphology, ATP content, membrane potential, and fusion/fission protein expression. 5-Fluorouracil induced ultra-structural mitochondrial damage in rat hearts, decreased mitochondrial membrane potential, increased fission proteins, and decreased fusion proteins.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: