Journal: Redox Biology

Article Title: Activation of CISD2 as a protective strategy against doxorubicin-induced cardiotoxicity

doi: 10.1016/j.redox.2025.103840

Figure Lengend Snippet: Doxorubicin (DOX) downregulates the expression of CISD2, while transgenic overexpression of CISD2 protects mice from DOX-induced cardiotoxicity. (A) DOX decreased the luciferase activity in the HEK293-CISD2 reporter cell line. However, Cisplatin, Taxol and Imatinib have no overt effects on the CISD2 reporter (n = 3). (B–C) The mRNA (B) and the protein (C) levels of Cisd2 were decreased in a dose-dependent manner in HL-1 mouse cardiomyocytes after DOX treatment for 24 h (n = 3). (D) The mRNA level of Cisd2 was decreased at 16 h in the cardiac muscle of DOX-treated mice after injection with a single dose of DOX (25 mg/kg) (n = 4 for control group, and n = 5 for DOX-treated group). (E) The level of Cisd2 in the Cisd2 overexpression (Cisd2-OE) stable line of HL-1 mouse cardiomyocytes was analyzed by Western blot. (F) Cisd2-OE improved DOX-induced mitochondrial dysfunction as monitored by JC-1 staining of mitochondrial membrane potential (n = 3). (G) Animal protocol for acute DOX-injury model (H–N). WT and Cisd2 transgenic (Cisd2TG) mice were injected with a single dose of DOX (25 mg/kg, i.p. injection). Cardiac function was monitored at day 4 (Echo) and day 5 (ECG) after DOX treatment. (H–I) Echocardiography (Echo) is used to measure the left ventricular ejection fraction and end-diastolic diameter. Representative echocardiographic (ECG) results (H) and the quantification data (I) from the WT and Cisd2TG mice are shown (n = 7 or 8 for each group). (J) Representative waterfall plots of ECG results of WT and Cisd2TG mice that received a single dose of DOX. (K–N) Cardiac electrical dysfunction was detected by ST elevation (K), heart rate (L), QTc (M) and T-peak-T-end (N) (n = 7 or 8 for each group). Data represent mean ± SD from at least three independent biological replicates per group, and the numbers are indicated as n. All data are analyzed by the Kruskal-Wallis test with the Dunn's test. ∗ p < 0.05, ∗∗ p < 0.005.

Article Snippet: ECG analysis was carried out impartially using LabChart 7 Pro version 7.3.1 (ADInstruments, Inc).

Techniques: Expressing, Transgenic Assay, Over Expression, Luciferase, Activity Assay, Injection, Control, Western Blot, Staining, Membrane

Journal: Redox Biology

Article Title: Activation of CISD2 as a protective strategy against doxorubicin-induced cardiotoxicity

doi: 10.1016/j.redox.2025.103840

Figure Lengend Snippet: The CISD2 activator hesperetin ameliorates DOX-induced cardiac dysfunctions without affecting the anti-cancer efficacy of DOX and hesperetin functions in a Cisd2-dependent manner. (A) Animal protocol for pharmaceutical approach using an acute DOX-injury model (B–I). Cisd2 f/f and Cisd2cKO mice were injected with a single dose of DOX (25 mg/kg, i.p. injection) with or without hesperetin treatment (10 mg/kg/day, i.p. injection). (B–C) The protein level of Cisd2 was detected by Western blot (n = 3–4). The mice used in this experiment are WT C57BL/6 males. (D) Echocardiography was used to measure the left ventricular ejection fraction and end-diastolic diameter. Representative echocardiographic images are shown. (E) Quantification results of the ejection fraction (n = 7 or 8). (F) Representative waterfall plots of the electrocardiographic results. (G) The cardiac electrical dysfunction was monitored by ST elevation (n = 7 or 8). (H) Serum levels of CKMB (n = 5–7). (I) Serum levels of Troponin I (n = 6). (J) Animal protocol for tumor-bearing mice (K–N). WT mice were implanted with LLC1 cells by subcutaneous (s.c.) injection and received six doses of DOX injection (5 mg/kg, i.p. injection) with or without hesperetin treatment. (K – L) Tumor volume (K) and tumor weight (L) were measured (n = 8 for each group). (M – N) Serum levels of CKMB (M) and serum troponin I (N) in different groups of tumor-bearing mice were examined (n = 8). V or Veh: vehicle control; Hes: hesperetin treatment. Data are presented as mean ± SD and are analyzed by the Kruskal-Wallis test with the Dunn's test. ∗ p < 0.05; ∗∗ p < 0.005.

Article Snippet: ECG analysis was carried out impartially using LabChart 7 Pro version 7.3.1 (ADInstruments, Inc).

Techniques: Injection, Western Blot, Control