Prolonged Diuretic, Natriuretic, and Potassium- and Calcium-Sparing Effect of Hesperidin in Hypertensive Rats

Area of Science:

• Pharmacology
• Nephrology
• Natural Products Chemistry

Background:

• Systemic hypertension is a significant global health issue linked to cardiovascular, cerebrovascular, and renal diseases.
• Diuretics are essential first-line antihypertensive treatments, but novel compounds with enhanced renal protection and unique mechanisms are needed.
• Hesperidin, a citrus flavonoid, is explored for its potential therapeutic benefits.

Purpose of the Study:

• To investigate the diuretic and renal protective effects of hesperidin in a rat model.
• To evaluate hesperidin's impact on electrolyte balance and kidney stone formation.
• To explore the potential mechanism of action involving the calcium-sensing receptor (CaSR).

Main Methods:

• Male spontaneously hypertensive and normotensive rats were administered hesperidin (3.0 mg/kg/day) for seven days.
• Urine analysis included electrolytes (Na+, K+, Cl-, Ca2+), biochemical parameters, and crystal precipitation assessment.
• Renal tissues were examined histologically, and molecular docking studies were performed for hesperetin (hesperidin's metabolite) with CaSR.

Main Results:

• Hesperidin induced significant diuretic and natriuretic effects.
• The treatment demonstrated potassium- and calcium-sparing properties.
• A notable decrease in calcium oxalate crystal formation and histological evidence of renal protection were observed in hypertensive rats.
• Docking studies suggested high binding affinity between hesperetin and CaSR.

Conclusions:

• Hesperidin exhibits promising diuretic and natriuretic properties with a favorable electrolyte-sparing profile.
• Hesperidin demonstrates potential in preventing urinary crystalluria and protecting renal tissue, particularly in hypertensive conditions.
• The interaction of hesperetin with CaSR may underlie its observed renal protective and anti-crystalluria effects, warranting further investigation.