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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

Schematic representation of the experimental procedure. Diabetic mouse model was induced by streptozotocin (STZ) injection. NAC treatment was done via drinking water starting from week 1, week 3, week 5 and week 7 STZ injection till the end of the week 12, respectively. Cardiac function and structure were analyzed by both echocardiography and histology
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Fig1: Schematic representation of the experimental procedure. Diabetic mouse model was induced by streptozotocin (STZ) injection. NAC treatment was done via drinking water starting from week 1, week 3, week 5 and week 7 STZ injection till the end of the week 12, respectively. Cardiac function and structure were analyzed by both echocardiography and histology

Mentions: Twelve-week-old male C57BL/6 mice from the Experimental Animal Center of the Fourth Military Medical University were housed five/cage under a temperature of 25 ± 1 °C, 50 ± 5 % humidity, with an alternating 12 hrs light–dark cycle and free access to food and water ad libitum. The type of housing facility was specific pathogen free (SPF), and the cage is 30 cm (width) × 40 cm (depth) × 20 cm (height). For STZ induced diabetes model, mice were injected intraperitoneally with streptozocin (150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer (citric acid and sodium citrate, pH 4.8) or vehicle (citrate buffer) after overnight fast similar as described before [9]. Blood glucose was checked 5 days later via tail vein; mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a control, mice were injected with equal volume of citrate buffer. In total, 35 mice were include in this study, which were divided into 7 groups with 5 animals in each group: including control, NAC only, DM (diabetes without NAC treatment), and 4 different NAC treatment groups. The 4 NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, define the start time point when NAC treatments start. For example, in the NAC1 groups, diabetic mice were treated with NAC (A9165, Sigma-Aldrich) from 1 week after STZ induction at the dose of 1.0 g/kg body weight per day in drinking water. In the NAC only group, control mice were further treated with NAC for five weeks. No obvious adverse events were seen in each experimental group. The detailed procedure described in Fig. 1.Fig. 1


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)

Schematic representation of the experimental procedure. Diabetic mouse model was induced by streptozotocin (STZ) injection. NAC treatment was done via drinking water starting from week 1, week 3, week 5 and week 7 STZ injection till the end of the week 12, respectively. Cardiac function and structure were analyzed by both echocardiography and histology
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4525750&req=5

Fig1: Schematic representation of the experimental procedure. Diabetic mouse model was induced by streptozotocin (STZ) injection. NAC treatment was done via drinking water starting from week 1, week 3, week 5 and week 7 STZ injection till the end of the week 12, respectively. Cardiac function and structure were analyzed by both echocardiography and histology
Mentions: Twelve-week-old male C57BL/6 mice from the Experimental Animal Center of the Fourth Military Medical University were housed five/cage under a temperature of 25 ± 1 °C, 50 ± 5 % humidity, with an alternating 12 hrs light–dark cycle and free access to food and water ad libitum. The type of housing facility was specific pathogen free (SPF), and the cage is 30 cm (width) × 40 cm (depth) × 20 cm (height). For STZ induced diabetes model, mice were injected intraperitoneally with streptozocin (150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer (citric acid and sodium citrate, pH 4.8) or vehicle (citrate buffer) after overnight fast similar as described before [9]. Blood glucose was checked 5 days later via tail vein; mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a control, mice were injected with equal volume of citrate buffer. In total, 35 mice were include in this study, which were divided into 7 groups with 5 animals in each group: including control, NAC only, DM (diabetes without NAC treatment), and 4 different NAC treatment groups. The 4 NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, define the start time point when NAC treatments start. For example, in the NAC1 groups, diabetic mice were treated with NAC (A9165, Sigma-Aldrich) from 1 week after STZ induction at the dose of 1.0 g/kg body weight per day in drinking water. In the NAC only group, control mice were further treated with NAC for five weeks. No obvious adverse events were seen in each experimental group. The detailed procedure described in Fig. 1.Fig. 1

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