The Therapeutic Potential of Phloretin
Implications for Diabetic Nephropathy and Oxidative Stress Management
DOI:
https://doi.org/10.58445/rars.289Keywords:
Diabetic Nephropathy, Diabetes, Oxidative Stress, GLUT2Abstract
Diabetes mellitus affects a significant portion of the global population, with approximately 463 million individuals living with the condition worldwide. Among the various complications associated with diabetes, diabetic nephropathy, a progressive kidney disease, poses a considerable burden on affected individuals, as approximately 40% of people with diabetes develop this condition.
Diabetic nephropathy, or diabetic kidney disease, impairs the kidneys' ability to filter blood, leading to symptoms like proteinuria and hypertension in its early stages. However, as the disease progresses, more severe complications such as chronic kidney disease (CKD) and end-stage renal disease (ESRD) may arise, necessitating dialysis or kidney transplantation. These complications can significantly impact a person's quality of life, causing fatigue, fluid retention, electrolyte imbalances, anemia, and an increased risk of cardiovascular problems.
Oxidative stress plays a crucial role in the development of diabetic kidney disease, with hyperglycemia triggering an imbalance between reactive oxygen species (ROS) production and neutralization in the kidney. This results in cellular damage and inflammation within the renal tissue.
Phloretin, a dihydrochalcone, has been studied for its potential to inhibit glucose transporter 2 (GLUT2) in cancerous tissues, preventing glucose absorption and metabolism. Beyond cancer cells, phloretin may also have physiological roles in the kidneys, such as mitigating glucose-induced ROS production and acting as an antioxidant by promoting the expression of antioxidant enzymes. Additionally, phloretin's chelation properties may help prevent complications related to heavy metal toxicity-induced diabetes mellitus, which contributes to diabetic nephropathy through oxidative stress.
This paper explores the positive potential of phloretin therapy for kidney function while acknowledging potential short-term damage to the liver and pancreas. To address these concerns, the paper suggests two concepts: 1) a metformin-based phloretin treatment plan and 2) maximizing the localization of phloretin to the kidneys to minimize off-target effects.
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