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N-Acetyl Cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition.

Liu C, Lu XZ, Shen MZ, Xing CY, Ma J, Duan YY, Yuan LJ - BMC Cardiovasc Disord (2015)

Bottom Line: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction.NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function.Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, #569 Xinsi Road, Baqiao District, Xi'an, 710038, China. 1821216564@qq.com.

ABSTRACT

Background: Diabetic cardiomyopathy is one of the leading causes of death in diabetes mellitus (DM) patients. This study aimed to explore the therapeutic implication of N-acetyl-L-cysteine (NAC, an antioxidant and glutathione precursor) and the possible underlying mechanism.

Methods: Thirty five 12-week-old male C57BL/6 mice were included. Twenty-five diabetic mice were induced by intraperitoneal injection of streptozocin (STZ, 150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer after overnight fast. Mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a non-DM (diabetic) control, mice were injected with equal volume of citrate buffer. The 25 diabetic mice were divided into 5 groups with 5 animals in each group: including DM (diabetes without NAC treatment), and 4 different NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, with the number defining the start time point of NAC treatment. In the 10 non-DM mice, mice were either untreated (Ctrl) or treated with NAC for 5 weeks (NAC only). Echocardiography was performed 12 weeks after STZ injection. Heart tissue were collected after echocardiography for Hematoxylin Eosin (HE) and Trichrome staining and ROS staining. Cardiac fibroblast cells were isolated, cultured and treated with high glucose plus NAC or the vehicle. qPCR analysis and CCK-8 assay were performed to observe fibrotic gene expression and cell proliferation.

Results: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction. NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function. Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis. In the cardiac fibroblasts, NAC blocked cardiac fibroblast proliferation and collagen synthesis induced by hyperglycemia.

Conclusions: Our study indicates that NAC treatment in diabetes effectively protects from diabetic cardiomyopathy, possibly through inhibiting the ROS production and fibrosis, which warrants further clarification.

No MeSH data available.


Related in: MedlinePlus

Effects of NAC on high glucose induced fibroblast proliferation and collagen expression. (a) Cardiac fibroblast cells were cultured in 5.5 mM glucose (NG) and 25 mM glucose (HG) w/o 5 mM NAC. Viable cell numbers were calculated by CCK-8 kit. *p<0.05, n=3. (b) Col1a1 gene expression in cardiac fibroblasts cultured in serum free medium with 10 ng/ml TGFβ1 containing 5.5 mM glucose, 25 mM glucose with/o 5 mM NAC. *p<0.05, n=3. (c) CTGF gene expression in cardiac fibroblasts treated same as above. *p<0.05, n=3
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Fig5: Effects of NAC on high glucose induced fibroblast proliferation and collagen expression. (a) Cardiac fibroblast cells were cultured in 5.5 mM glucose (NG) and 25 mM glucose (HG) w/o 5 mM NAC. Viable cell numbers were calculated by CCK-8 kit. *p<0.05, n=3. (b) Col1a1 gene expression in cardiac fibroblasts cultured in serum free medium with 10 ng/ml TGFβ1 containing 5.5 mM glucose, 25 mM glucose with/o 5 mM NAC. *p<0.05, n=3. (c) CTGF gene expression in cardiac fibroblasts treated same as above. *p<0.05, n=3

Mentions: Per the overt effects of NAC on cardiac fibrosis, we next tested the role of NAC on cardiac fibroblast proliferation and collagen synthesis. Isolated cardiac fibroblast cells were cultured in normal and high glucose medium. Compared with the normal glucose medium, high glucose slightly stimulated the fibroblast proliferation, which was totally blocked by NAC treatment (Fig. 5a). Besides the pro-proliferative role of high glucose on cardiac fibroblasts, high glucose also increased TGFβ1 induced expression of Col1a1 and CTGF (Fig. 5b-c). Again, NAC attenuated the Col1a1 and CTGF expression induced by TGFβ1.Fig. 5


N-Acetyl Cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition.

Liu C, Lu XZ, Shen MZ, Xing CY, Ma J, Duan YY, Yuan LJ - BMC Cardiovasc Disord (2015)

Effects of NAC on high glucose induced fibroblast proliferation and collagen expression. (a) Cardiac fibroblast cells were cultured in 5.5 mM glucose (NG) and 25 mM glucose (HG) w/o 5 mM NAC. Viable cell numbers were calculated by CCK-8 kit. *p<0.05, n=3. (b) Col1a1 gene expression in cardiac fibroblasts cultured in serum free medium with 10 ng/ml TGFβ1 containing 5.5 mM glucose, 25 mM glucose with/o 5 mM NAC. *p<0.05, n=3. (c) CTGF gene expression in cardiac fibroblasts treated same as above. *p<0.05, n=3
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4525750&req=5

Fig5: Effects of NAC on high glucose induced fibroblast proliferation and collagen expression. (a) Cardiac fibroblast cells were cultured in 5.5 mM glucose (NG) and 25 mM glucose (HG) w/o 5 mM NAC. Viable cell numbers were calculated by CCK-8 kit. *p<0.05, n=3. (b) Col1a1 gene expression in cardiac fibroblasts cultured in serum free medium with 10 ng/ml TGFβ1 containing 5.5 mM glucose, 25 mM glucose with/o 5 mM NAC. *p<0.05, n=3. (c) CTGF gene expression in cardiac fibroblasts treated same as above. *p<0.05, n=3
Mentions: Per the overt effects of NAC on cardiac fibrosis, we next tested the role of NAC on cardiac fibroblast proliferation and collagen synthesis. Isolated cardiac fibroblast cells were cultured in normal and high glucose medium. Compared with the normal glucose medium, high glucose slightly stimulated the fibroblast proliferation, which was totally blocked by NAC treatment (Fig. 5a). Besides the pro-proliferative role of high glucose on cardiac fibroblasts, high glucose also increased TGFβ1 induced expression of Col1a1 and CTGF (Fig. 5b-c). Again, NAC attenuated the Col1a1 and CTGF expression induced by TGFβ1.Fig. 5

Bottom Line: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction.NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function.Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, #569 Xinsi Road, Baqiao District, Xi'an, 710038, China. 1821216564@qq.com.

ABSTRACT

Background: Diabetic cardiomyopathy is one of the leading causes of death in diabetes mellitus (DM) patients. This study aimed to explore the therapeutic implication of N-acetyl-L-cysteine (NAC, an antioxidant and glutathione precursor) and the possible underlying mechanism.

Methods: Thirty five 12-week-old male C57BL/6 mice were included. Twenty-five diabetic mice were induced by intraperitoneal injection of streptozocin (STZ, 150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer after overnight fast. Mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a non-DM (diabetic) control, mice were injected with equal volume of citrate buffer. The 25 diabetic mice were divided into 5 groups with 5 animals in each group: including DM (diabetes without NAC treatment), and 4 different NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, with the number defining the start time point of NAC treatment. In the 10 non-DM mice, mice were either untreated (Ctrl) or treated with NAC for 5 weeks (NAC only). Echocardiography was performed 12 weeks after STZ injection. Heart tissue were collected after echocardiography for Hematoxylin Eosin (HE) and Trichrome staining and ROS staining. Cardiac fibroblast cells were isolated, cultured and treated with high glucose plus NAC or the vehicle. qPCR analysis and CCK-8 assay were performed to observe fibrotic gene expression and cell proliferation.

Results: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction. NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function. Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis. In the cardiac fibroblasts, NAC blocked cardiac fibroblast proliferation and collagen synthesis induced by hyperglycemia.

Conclusions: Our study indicates that NAC treatment in diabetes effectively protects from diabetic cardiomyopathy, possibly through inhibiting the ROS production and fibrosis, which warrants further clarification.

No MeSH data available.


Related in: MedlinePlus