Anti-Hyperglycemic Effect of Magnesium-Enhanced Alkaline-Reduced Water on High Glucose-Induced Oxidative Stress in Renal Tubular Epithelial Cells

Abstract

Diabetes is coupled with hyperglycemia, a state in which elevated glucose levels trigger oxidative stress (OS) in various body functions. One of the organs most afflicted by diabetes is the kidney. Despite this, specific treatments to mitigate the harmful effects of hyperglycemia-induced OS in the kidney have not been extensively explored. This study evaluates the anti-hyperglycemic efficacy of magnesium-enhanced alkaline-reduced water (MARW) in human kidney-2 (HK-2) cells. OS, mitogen-activated protein kinase (MAPK) signaling and fibrosis markers were assessed in high glucose (HG)-induced HK-2 cells, followed by treatment with experimental water for 24 h. Surprisingly, MARW rescued the vitality of HG-induced HK-2 cells, in contrast to that seen with other experimental waters. Additionally, MARW maintained reactive oxygen species, nitric oxide, catalase, glutathione peroxidase, hepatocyte growth factor and glucose uptake in HG-induced HK-2 cells but not in tap water and mineral water. Similarly, MARW downregulated the expression of MAPK and fibrosis-linked signaling proteins such as p-p38, phospho-c-Jun N-terminal kinase, α-smooth muscle actin, matrix metalloproteinase-3 and cleaved caspase 3 in HG-induced HK-2 cells. In conclusion, MARW protects HK-2 cells from the deleterious effects of HG by stabilizing antioxidant defenses and by signaling cascades related to metabolism, apoptosis and fibrosis.

Study details

Article type

Original Research

Disease / injury model

High glucose-induced oxidative stress in renal tubular epithelial cells (in vitro model of diabetic nephropathy)

Dose comparison

The study used a fixed high glucose concentration (71.68 mM) to induce oxidative stress and compared the effects of different water treatments (10% TW, MW, MARW) on cell viability and biochemical markers.

Dose-dependent effect

No

Outcome

Positive

Findings

Magnesium-enhanced alkaline-reduced water (MARW) protected human kidney-2 (HK-2) cells from high glucose-induced oxidative stress by stabilizing antioxidant defenses, reducing apoptosis, and downregulating MAPK and fibrosis-related signaling proteins. MARW was more effective than tap water or mineral water in maintaining cell viability, reducing ROS and NO, enhancing GPx and CAT activities, restoring HGF levels, and reducing pro-inflammatory cytokines.