Pyridoxamine combats heart damage in prediabetes

Cardiology Updates: Researchers from various prestigious institutions have discovered promising effects of pyridoxamine, a vitamin B6 analog, in alleviating heart damage caused by a Western diet in prediabetic rats. This Cardiology Updates news report delves into the study and its significant findings, making it comprehensible for everyone.


Pyridoxamine combats heart damage in prediabetes

The Challenge of Heart Disease in Diabetes
More than 536 million people worldwide suffer from diabetes mellitus, with numbers rising rapidly. Individuals with type 2 diabetes mellitus (T2DM) are particularly susceptible to cardiovascular diseases (CVD). Diabetic cardiomyopathy (DCM), a condition that includes structural and functional changes in the heart, is a serious complication of diabetes. This condition can lead to heart failure, significantly impacting the quality of life and survival of affected individuals.
 
Study Overview
In this study, researchers sought to explore whether pyridoxamine could mitigate adverse cardiac remodeling and dysfunction in a rat model of prediabetes induced by a Western diet. The research was conducted by scientists from UHasselt-Belgium, Maastricht University Medical Centre-Netherlands and Stellenbosch University-South Africa.
 
Methodology
Rat Model and Diets
The researchers used male rats, which were divided into three groups. The first group received a standard chow diet, the second group was fed a high-sugar Western diet (WD) to induce prediabetes, and the third group received the WD supplemented with pyridoxamine in their drinking water. The study lasted for 18 weeks.
 
Assessments and Measurements
To evaluate the impact of the diets and pyridoxamine supplementation, the researchers performed various tests and measurements. These included oral glucose tolerance tests (OGTT) to assess glucose metabolism, echocardiography to examine heart structure and function, and histological analyses to evaluate heart tissue.
 
Key Findings
-Impact on Blood Sugar Levels
One of the significant findings of this study was that pyridoxamine supplementation helped maintain normal fasting blood glucose levels in WD-fed rats. Elevated blood glucose levels are a major risk factor for developing diabetes and its associated complications, making this finding particularly relevant.
 
-Cardiac Function and Structure
The researchers observed that the WD-fed rats without pyridoxamine supplementation exhibited significant heart enlargement, particularly in the left ventricle (LV). This enlargement, or dilation, is a common issue in people with diabetes and can lead to heart failure. Echocardiographic assessments revealed that pyridoxamine significantly reduced LV dilation and end-systolic volume, indicating better heart health.
 
-Reduction in Heart Fibrosis
Fibrosis, or the thickening and scarring of connective tissue, is another severe concern for individuals with diabetes. It can lead to a stiffer heart muscle, impairing its ability to function effectively. The study found that pyridoxamine significantly reduced the amount of collagen deposition in the heart, a marker of fibrosis. This suggests that pyridoxamine can help maintain the heart muscle's flexibility and functionality.
 
Detailed Mechanisms
-Antioxidant Effects
Pyridoxamine’s ability to reduce oxidative stress in the heart was another crucial discovery. Oxidative stress occurs when there is an imbalance between free radicals and antioxidants, leading to cell damage. The study demonstrated that pyridoxamine decreased levels of harmful compounds like 3-nitrotyrosine and 4-hydroxynonenal (4-HNE) in the heart. These compounds are indicators of oxidative stress, and their reduction points to the protective antioxidant effects of pyridoxamine.
 
-Gene Expression Modulation
The study also examined how pyridoxamine affected the expression of genes related to heart health. Researchers found that pyridoxamine reduced the expression of the gene for nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), an enzyme involved in producing harmful superoxide radicals. This reduction suggests that pyridoxamine helps lower oxidative stress and potential damage to the heart.
 
Comprehensive Insights
-Body Weight and Organ Weights
The WD led to significant body weight gain compared to the standard chow diet. However, pyridoxamine did not affect body weight gain in the WD-fed rats. The study also observed elevated heart and liver weights in WD-fed rats, with or without pyridoxamine supplementation. Interestingly, pyridoxamine did not prevent the WD-induced increase in body, heart, and liver weight.
 
-Glucose Tolerance and Insulin Levels
WD-fed rats showed significantly lower glucose tolerance compared to those on the chow diet. Pyridoxamine administration seemed to improve glucose tolerance after 12 and 18 weeks, although the improvement was not statistically significant. Additionally, pyridoxamine prevented the increase in fasting plasma glucose levels seen in WD-fed rats. However, there were no significant changes in fasting plasma insulin levels among the groups.
 
In-Depth Cardiac Evaluations
-Echocardiography Results
Echocardiography was performed after 18 weeks to assess in vivo LV cardiac function. The WD group showed increased systolic area and end-systolic volume, which were attenuated with pyridoxamine administration. Although the WD group tended to have a reduced ejection fraction (EF), this was not significantly improved with pyridoxamine treatment. Other echocardiographic parameters for LV hypertrophy, such as wall thickness and internal diameters, remained similar among all groups.
 
-Histological and Gene Expression Analyses
LV tissue sections stained with Sirius Red/Fast Green showed that pyridoxamine significantly prevented an increase in interstitial collagen deposition seen in WD-fed rats. Additionally, pyridoxamine downregulated the expression of collagen type I gene in the LV tissue of WD-fed rats. Hematoxylin and eosin staining revealed an increased cross-sectional cardiomyocyte area (CSA) in the WD + PM group compared to the chow diet group.
 
-Oxidative Stress Markers
Staining for oxidative stress markers, 3-nitrotyrosine, and 4-HNE showed that pyridoxamine reduced their deposition in the LV tissue. This reduction suggests that pyridoxamine helps mitigate oxidative stress in the heart. Furthermore, pyridoxamine significantly decreased the gene expression of NOX4 in the LV tissue, aligning with its role in reducing oxidative stress.
 
Conclusions and Future Directions
This study provides compelling evidence that pyridoxamine can significantly reduce heart damage in prediabetic rats fed a Western diet. By lowering blood sugar levels, reducing heart enlargement and fibrosis, and combating oxidative stress, pyridoxamine shows potential as a protective agent against heart disease in diabetes.
 
These findings are groundbreaking, offering a new approach to preventing and treating heart complications in diabetes.
 
The results were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/15/8508
 
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