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Fig 1.

Molecular structure of trillin.

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Fig 2.

Trillin improved DOX-induced cardiac dysfunction in C57 mice.

(A) Schematic protocol for DOX and trillin treatment. (B-G) Echocardiography parameters of HR, LVEF, LVFS, SV, LVIDs, and LVIDd in mice (n = 8). #P < 0.05, ##P < 0.01 vs control; * P < 0.05, vs DOX.

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Fig 3.

Trillin alleviated DOX-induced cardiac injury in mice.

(A-C) Serum levels of CK-MB, LDH, and AST in mice (n = 8). (D-E) Body weight and heart weight of the mice. (F) Cell edema index of myocardial cells in mice. (G) Representative images of H&E staining, (Scale bar = 50 μm). ##P < 0.01 vs control; * P < 0.05, **P < 0.01 vs DOX.

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Fig 4.

Effects of trillin on H9c2 cells viability and antitumor ability of DOX.

(A) Cytotoxicity of trillin on H9c2 cells. (B) H9c2 cells were co-treated with DOX (4 μM) and trillin (0.25, 0.5, 1, 2, 4, 8, 16 and 20 μM) for 24 hours. (C-D) Levels of LDH and cTnT in H9c2 cells. (E-G) H460, HepG2, and 4T1 cells were co-treated with DOX (4 μM) and trillin (0.5, 1 and 2 μM) for 24 hours. (n = 6). ##P < 0.01 vs control; * P < 0.05, **P < 0.01 vs DOX.

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Fig 4 Expand

Fig 5.

Trillin attenuated DOX-induced oxidative stress.

(A-D) CAT, GSH, SOD, and MDA lvels in cardiac tissue of mice. (E-H) CAT, GSH, SOD, and MDA levels in H9c2 cells (n = 6). ##P < 0.01 vs control; * P < 0.05, **P < 0.01 vs DOX.

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Fig 5 Expand

Fig 6.

Trillin increased Nrf2 expression.

(A-B) The mRNA levels of Nrf2 and HO-1 in mice. (C-D) The protein level of Nrf2 in mice (n = 3). (E-F) The mRNA levels of Nrf2 and HO-1 in H9c2 cells. (G-H) The protein level of Nrf2 in H9c2 cells (n = 3). (I-K) After inhibiting of Nrf2 gene expression in cardiomyocytes, the protein level of Nrf2 in H9c2 cells (n = 3). ##P < 0.01 vs control; * P < 0.05, **P < 0.01 vs DOX; $$P < 0.01 vs DOX+ML385.

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Fig 6 Expand