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Effect of Riociguat on Adenine-Induced Chronic Kidney Disease in Rats
Aly M Abdelrahman1, Raya Al Maskari1, Haytham Ali2
1Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Oman.
Biology
|February 26, 2025
Summary
Riociguat, a soluble guanylate cyclase activator, demonstrated protective effects in a rat model of chronic kidney disease (CKD). It reduced kidney damage, inflammation, and oxidative stress, suggesting potential for slowing CKD progression.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Cyclic guanosine monophosphate (cGMP) plays a crucial role in regulating kidney function.
- Chronic kidney disease (CKD) is characterized by progressive kidney damage and impaired function.
- Soluble guanylate cyclase (sGC) activators, like riociguat, increase cGMP levels.
Purpose of the Study:
- To investigate the potential renoprotective effects of riociguat in a rat model of chronic kidney disease (CKD).
- To evaluate the impact of riociguat on kidney function markers, inflammation, and oxidative stress in adenine-induced CKD.
Main Methods:
- Chronic kidney disease (CKD) was induced in male Wistar rats using adenine administration.
- Rats were divided into four groups: control, adenine-only, and adenine plus two doses of riociguat (3 mg/kg/day and 10 mg/kg/day).
- Treatments were administered over 35 days, with assessments of blood pressure, kidney function markers, inflammatory cytokines, oxidative stress markers, and histopathological changes.
Main Results:
- Adenine-induced CKD significantly increased systolic blood pressure, plasma creatinine, urea, NGAL, urinary albumin-to-creatinine ratio, and NAG, while reducing creatinine clearance.
- Histopathology revealed renal tubular necrosis and fibrosis in adenine-treated rats, alongside elevated IL-1β, IL-6, TNF-α, and MDA, and reduced antioxidant capacity (GR, SOD, CAT, TAC).
- Riociguat treatment attenuated hypertension, improved kidney function, reduced kidney injury markers, decreased inflammation and oxidative stress, and ameliorated histopathological damage.
Conclusions:
- Riociguat demonstrated significant renoprotective effects in adenine-induced chronic kidney disease (CKD) in rats.
- The protective mechanisms likely involve anti-inflammatory and antioxidant actions, mitigating renal damage.
- Riociguat holds potential as a therapeutic agent to slow the progression of kidney damage in chronic kidney disease (CKD).
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