Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation
Abstract
1. Introduction
2. Methods
3. Uric Acid: Metabolism and Physiological Implications
4. Uric Acid in Pregnancy
5. Hyperuricemia and Preeclampsia
6. Diagnostic and Predictive Value of Uric Acid in Preeclampsia
7. The NLRP3 Inflammasome as a Potential Contributor to the Pathophysiology of Preeclampsia
7.1. NLRP3 Inflammasome and Pregnancy
7.2. Evidence of NLRP3 Activation in Preeclampsia
7.3. Renal NLRP3 Inflammasome Activation in Hypertension: Implications for Preeclampsia Pathophysiology
7.4. NLRP3 Inflammasome as a Mediator of Endothelial Dysfunction: Implications for Preeclampsia Pathophysiology
8. Uric Acid and NLRP3 Inflammasome Activation
9. Uric Acid and NLRP3 Inflammasome as Targets of Preeclampsia
AGENT | MECHANISM OF ACTION | LEVEL OF EVIDENCE | USE IN PREGNANCY | REGULATORY STATUS |
---|---|---|---|---|
ALLOPURINOL | Inhibits xanthine oxidase, blocking uric acid and reactive oxygen species production [125,126]. | Preclinical and some clinical studies in women with preeclampsia (PE) or cardiovascular risk [143,144]. | Documented off-label use in pregnant women; no major teratogenic effects reported [144]. | Approved for hyperuricemia and gout; off-label use in PE. FDA Category C: Risk cannot be ruled out. |
METFORMIN | Activates AMPK; improves insulin sensitivity and exerts anti-inflammatory effects. Indirectly inhibits NLRP3 [100,141]. | Strong clinical evidence in gestational diabetes; beneficial effects in PE animal models [100,141]. | Widely used during pregnancy; considered safe by international guidelines (ACOG, NICE). | Approved by FDA and EMA; widely used in pregnancy. FDA Category B: No evidence of harm in humans. |
MCC950 | Specific NLRP3 inhibitor; blocks inflammasome oligomerization and IL-1β/IL-18 release [134,135,136]. | Efficacy shown in animal models of salt-sensitive hypertension and PE. No clinical trials in humans [134,135,136]. | Not evaluated in pregnant women; promising preclinical results. | Not approved; in preclinical phase. Clinical development halted due to hepatotoxicity. |
ANAKINRA | Recombinant IL-1 receptor antagonist; blocks IL-1α and IL-1β signaling, reducing inflammatory cytokine activation and NLRP3 inflammasome downstream effects [139]. | Antihypertensive effect in animal models. Modest reduction in diastolic blood pressure and confirmed anti-inflammatory effects in humans following acute coronary syndrome [138,139]. | No large studies in hypertensive pregnant women. | Approved for inflammatory diseases such as rheumatoid arthritis. FDA Category B: No evidence of risk in humans, but caution is advised. Off-label use in cardiovascular disease. |
10. Conclusion and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Arias-Sánchez, C.; Pérez-Olmos, A.; Reverte, V.; Hernández, I.; Cuevas, S.; Llinás, M.T. Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation. Antioxidants 2025, 14, 928. https://doi.org/10.3390/antiox14080928
Arias-Sánchez C, Pérez-Olmos A, Reverte V, Hernández I, Cuevas S, Llinás MT. Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation. Antioxidants. 2025; 14(8):928. https://doi.org/10.3390/antiox14080928
Chicago/Turabian StyleArias-Sánchez, Celia, Antonio Pérez-Olmos, Virginia Reverte, Isabel Hernández, Santiago Cuevas, and María Teresa Llinás. 2025. "Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation" Antioxidants 14, no. 8: 928. https://doi.org/10.3390/antiox14080928
APA StyleArias-Sánchez, C., Pérez-Olmos, A., Reverte, V., Hernández, I., Cuevas, S., & Llinás, M. T. (2025). Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation. Antioxidants, 14(8), 928. https://doi.org/10.3390/antiox14080928