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SOTA alleviates DOX-induced cardiotoxicity and cardiomyocyte apoptosis in vitro . (A) Cell viability of H9c2 cells treated with DOX (0, 5, 10, 20 and 30 µM) at 12 h. (B) Cell viability of H9c2 cells treated with DOX (10 µM) combined with SOTA (0, 5, 10, 20 and 40 µM) at 12 h. (C) LDH levels in H9c2 cells were detected by a commercial ELISA kit. (D) Representative TUNEL staining images and (E) the quantitative results of H9c2 cells. Scale bar, 20 µm. (F) Statistical results of C cas-3, Bax and Bcl-2 proteins of H9c2 cells and (G) representative images of western blotting. All data are expressed as the mean ± SD (n=3). * P<0.05, ** P<0.01 compared with Control untreated groups, # P<0.05 and ## P<0.01 compared with DOX alone group. ns, not significant; SOTA, sotagliflozin; DOX, doxorubicin; C cas-3, cleaved capsase-3; LDH, lactate dehydrogenase.

Journal: Experimental and Therapeutic Medicine

Article Title: Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway

doi: 10.3892/etm.2026.13201

Figure Lengend Snippet: SOTA alleviates DOX-induced cardiotoxicity and cardiomyocyte apoptosis in vitro . (A) Cell viability of H9c2 cells treated with DOX (0, 5, 10, 20 and 30 µM) at 12 h. (B) Cell viability of H9c2 cells treated with DOX (10 µM) combined with SOTA (0, 5, 10, 20 and 40 µM) at 12 h. (C) LDH levels in H9c2 cells were detected by a commercial ELISA kit. (D) Representative TUNEL staining images and (E) the quantitative results of H9c2 cells. Scale bar, 20 µm. (F) Statistical results of C cas-3, Bax and Bcl-2 proteins of H9c2 cells and (G) representative images of western blotting. All data are expressed as the mean ± SD (n=3). * P<0.05, ** P<0.01 compared with Control untreated groups, # P<0.05 and ## P<0.01 compared with DOX alone group. ns, not significant; SOTA, sotagliflozin; DOX, doxorubicin; C cas-3, cleaved capsase-3; LDH, lactate dehydrogenase.

Article Snippet: H9c2 cells were obtained from Procell Life Science & Technology Co., Ltd.

Techniques: In Vitro, Enzyme-linked Immunosorbent Assay, TUNEL Assay, Staining, Western Blot, Control

SOTA attenuates DOX-induced cardiac inflammation and ROS in vitro . (A) IL-6, IL-1β and TNF-α levels in H9c2 cells as determined by commercial ELISA kits. (B) Representative images of DCFH-DA staining and (C) the quantitative results of ROS levels in H9c2 cells. All data are expressed as the mean ± SD (n=3). Scale bar, 25 µm. ** P<0.01 compared with Control untreated group; ## P<0.01 compared with DOX alone group. SOTA, sotagliflozin; DOX, doxorubicin; DCFH-DA, 2',7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; DAPI, 4',6-diamidino-2-phenylindole.

Journal: Experimental and Therapeutic Medicine

Article Title: Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway

doi: 10.3892/etm.2026.13201

Figure Lengend Snippet: SOTA attenuates DOX-induced cardiac inflammation and ROS in vitro . (A) IL-6, IL-1β and TNF-α levels in H9c2 cells as determined by commercial ELISA kits. (B) Representative images of DCFH-DA staining and (C) the quantitative results of ROS levels in H9c2 cells. All data are expressed as the mean ± SD (n=3). Scale bar, 25 µm. ** P<0.01 compared with Control untreated group; ## P<0.01 compared with DOX alone group. SOTA, sotagliflozin; DOX, doxorubicin; DCFH-DA, 2',7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; DAPI, 4',6-diamidino-2-phenylindole.

Article Snippet: H9c2 cells were obtained from Procell Life Science & Technology Co., Ltd.

Techniques: In Vitro, Enzyme-linked Immunosorbent Assay, Staining, Control

SOTA attenuates DOX-induced cardiac mitochondrial dysfunction in vitro. (A) Representative images of Rhod2-AM staining and (B) mitochondrial Ca 2+ quantitative results in H9c2 cells. Scale bar, 25 µm . (C) H 2 O 2 levels in H9c2 cells as determined by commercial ELISA kits. (D) Representative images of JC-1 staining and (E) statistical results of JC-1 aggregates to monomers in H9c2 cells. Scale bar, 25 µm . (F) ATP levels in H9c2 cells as determined by ELISA kits. All data are expressed as the mean ± SD (n=3). ** P<0.01 compared with Control untreated group, # P<0.05 and ## P<0.01 compared with DOX alone group. SOTA, sotagliflozin; DOX, doxorubicin; H2O2, hydrogen peroxide; JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; DAPI, 4',6-diamidino-2-phenylindole; ATP, adenosine triphosphate.

Journal: Experimental and Therapeutic Medicine

Article Title: Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway

doi: 10.3892/etm.2026.13201

Figure Lengend Snippet: SOTA attenuates DOX-induced cardiac mitochondrial dysfunction in vitro. (A) Representative images of Rhod2-AM staining and (B) mitochondrial Ca 2+ quantitative results in H9c2 cells. Scale bar, 25 µm . (C) H 2 O 2 levels in H9c2 cells as determined by commercial ELISA kits. (D) Representative images of JC-1 staining and (E) statistical results of JC-1 aggregates to monomers in H9c2 cells. Scale bar, 25 µm . (F) ATP levels in H9c2 cells as determined by ELISA kits. All data are expressed as the mean ± SD (n=3). ** P<0.01 compared with Control untreated group, # P<0.05 and ## P<0.01 compared with DOX alone group. SOTA, sotagliflozin; DOX, doxorubicin; H2O2, hydrogen peroxide; JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; DAPI, 4',6-diamidino-2-phenylindole; ATP, adenosine triphosphate.

Article Snippet: H9c2 cells were obtained from Procell Life Science & Technology Co., Ltd.

Techniques: In Vitro, Staining, Enzyme-linked Immunosorbent Assay, Control

SOTA attenuates DOX-induced cardiomyocyte apoptosis by activating the AMPK/mTOR pathway in vitro . H9c2 cells were treated concomitantly with DOX and SOTA and with 10 µM of the AMPK/mTOR pathway inhibitor compound C. (A) Representative images of western blotting and (B) statistical results of p-AMPK/AMPK and p-mTOR/mTOR proteins in H9c2 cells treated with different concentrations of DOX. (C) Representative images of western blotting and (D) statistical results of p-AMPK/AMPK and p-mTOR/mTOR proteins in the presence of compound C. (E) Statistical results of C cas-3 and (F) Bcl-2/Bax proteins. (G) Quantitative results of H9c2 cells and (H) representative images of TUNEL staining. Scale bar, 20 µm . All data are expressed as the mean ± SD (n=3). * P<0.05, ** P<0.01 compared with DOX group, # P<0.05 and ## P<0.01 compared with SOTA + DOX group. SOTA, sotagliflozin; DOX, doxorubicin; p-, phosphorylated; AMPK, 5' AMP-activated protein kinase; C cas-3, cleaved caspase 3; mTOR, mechanistic target of rapamycin; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4',6-diamidino-2-phenylindole; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

Journal: Experimental and Therapeutic Medicine

Article Title: Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway

doi: 10.3892/etm.2026.13201

Figure Lengend Snippet: SOTA attenuates DOX-induced cardiomyocyte apoptosis by activating the AMPK/mTOR pathway in vitro . H9c2 cells were treated concomitantly with DOX and SOTA and with 10 µM of the AMPK/mTOR pathway inhibitor compound C. (A) Representative images of western blotting and (B) statistical results of p-AMPK/AMPK and p-mTOR/mTOR proteins in H9c2 cells treated with different concentrations of DOX. (C) Representative images of western blotting and (D) statistical results of p-AMPK/AMPK and p-mTOR/mTOR proteins in the presence of compound C. (E) Statistical results of C cas-3 and (F) Bcl-2/Bax proteins. (G) Quantitative results of H9c2 cells and (H) representative images of TUNEL staining. Scale bar, 20 µm . All data are expressed as the mean ± SD (n=3). * P<0.05, ** P<0.01 compared with DOX group, # P<0.05 and ## P<0.01 compared with SOTA + DOX group. SOTA, sotagliflozin; DOX, doxorubicin; p-, phosphorylated; AMPK, 5' AMP-activated protein kinase; C cas-3, cleaved caspase 3; mTOR, mechanistic target of rapamycin; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4',6-diamidino-2-phenylindole; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

Article Snippet: H9c2 cells were obtained from Procell Life Science & Technology Co., Ltd.

Techniques: In Vitro, Western Blot, TUNEL Assay, Staining

SOTA attenuates DOX-induced cardiac mitochondrial dysfunction by activating the AMPK/mTOR pathway in vitro . (A) Representative images of DCFH-DA staining and (B) representative images of JC-1 staining in H9c2 cells. (C) Quantitative results of ROS levels. (D) Quantitative mitochondrial Ca 2+ levels in H9c2 cells. (E) Statistical results of the ratio of JC-1 aggregates to monomers. All data are expressed as the mean ± SD (n=3). ** P<0.01 compared with DOX group, # P<0.05 and ## P<0.01 compared with SOTA + DOX group. SOTA, sotagliflozin; mTOR, mechanistic target of rapamycin; DOX, doxorubicin; DCFH-DA, 2',7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; DAPI, 4',6-diamidino-2-phenylindole.

Journal: Experimental and Therapeutic Medicine

Article Title: Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway

doi: 10.3892/etm.2026.13201

Figure Lengend Snippet: SOTA attenuates DOX-induced cardiac mitochondrial dysfunction by activating the AMPK/mTOR pathway in vitro . (A) Representative images of DCFH-DA staining and (B) representative images of JC-1 staining in H9c2 cells. (C) Quantitative results of ROS levels. (D) Quantitative mitochondrial Ca 2+ levels in H9c2 cells. (E) Statistical results of the ratio of JC-1 aggregates to monomers. All data are expressed as the mean ± SD (n=3). ** P<0.01 compared with DOX group, # P<0.05 and ## P<0.01 compared with SOTA + DOX group. SOTA, sotagliflozin; mTOR, mechanistic target of rapamycin; DOX, doxorubicin; DCFH-DA, 2',7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; DAPI, 4',6-diamidino-2-phenylindole.

Article Snippet: H9c2 cells were obtained from Procell Life Science & Technology Co., Ltd.

Techniques: In Vitro, Staining