Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells

Area of Science:

• Nephrology
• Pharmacology
• Cell Biology

Background:

• Diabetic nephropathy (DN) is a major complication of diabetes.
• Antidepressants like maprotiline can cause hypoglycemia.
• The impact of maprotiline on DN is not well understood.

Purpose of the Study:

• To investigate the protective effects of maprotiline on human renal glomerular endothelial cells (HRGECs) under high glucose conditions.
• To elucidate the underlying mechanisms of maprotiline's action in response to hyperglycemia.

Main Methods:

• Utilized human renal glomerular endothelial cells (HRGECs) exposed to high glucose (HG).
• Assessed oxidative stress markers, including reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.
• Measured the expression of cyclooxygenase-2 (COX-2), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), zonula occludens-1 (ZO-1), and protein kinase C-α (PKC-α).
• Evaluated cell permeability and the effect of PKC-α overexpression.

Main Results:

• Maprotiline reduced HG-induced oxidative stress by decreasing ROS production and increasing SOD activity.
• Maprotiline inhibited HG-induced COX-2 expression and normalized TXB2 and 6-keto-PGF1α levels.
• Maprotiline prevented HG-induced increases in HRGEC permeability and decreases in ZO-1 expression.
• Maprotiline downregulated HG-induced PKC-α expression, and its protective effects were abolished by PKC-α overexpression.

Conclusions:

• Maprotiline exerts protective effects against high glucose-induced damage in HRGECs.
• These protective effects are mediated through the regulation of PKC-α signaling pathways.
• Maprotiline shows potential as a therapeutic agent for diabetic nephropathy.