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Breaking the Calcium Overload Cycle in Acute Pancreatitis: Emerging Pharmacological Strategies
Serge Chooklin1, Serhii Chuklin2
1Surgical Center, Saint Paraskeva Medical Center, Lviv, Ukraine. chooklin_serge@hotmail.com.
Purpose:
To analyze current experimental and clinical studies regarding the role of calcium dysregulation in the pathogenesis of AP and to evaluate the efficacy of various pharmacological approaches to its correction.
Methods:
A literature review was conducted using PubMed, Scopus, and Google Scholar databases up to October 2025. Included were in vitro, in vivo, and clinical studies addressing the mechanisms of calcium imbalance in AP and the effects of different pharmacological agents targeting calcium regulation.
Results:
Key molecular targets for calcium-targeted therapy were identified, including IP3 and ryanodine receptors, SOC/CRAC channels, TMEM16A, the PI3K/Akt pathway, and the calcineurin/NFAT signaling cascade. Therapeutic compounds such as caffeine, dantrolene, docosahexaenoic acid (DHA), Orai1 channel inhibitors (CM4620/Auxora, GSK-7975A), TMEM16A inhibitors, insulin, calcium chelators (BAPTA-AM), calcineurin inhibitors (cyclosporin A, tacrolimus), and microRNAs (e.g., miR-26a) demonstrated the ability to reduce cytosolic calcium overload, suppress zymogen activation, stabilize mitochondrial function, and attenuate inflammation. Some of these agents are already used in other medical fields or are undergoing clinical trials as candidate treatments for AP.
Conclusions:
Pharmacological modulation of calcium homeostasis represents a promising pathogenetic approach to the treatment of acute pancreatitis. Existing evidence supports the need for further multicenter clinical studies to confirm the safety and efficacy of calcium-targeted strategies in routine clinical practice.
Insights
Calcium dysregulation is key in acute pancreatitis (AP). Targeting calcium pathways with drugs like dantrolene and Orai1 inhibitors shows promise for AP treatment, warranting further clinical studies.
Area of Science:
- Gastroenterology and Molecular Medicine
- Cellular Biology and Pharmacology
Background:
- Calcium dysregulation is a critical factor in the development of acute pancreatitis (AP).
- Understanding the molecular mechanisms of calcium imbalance is essential for developing effective treatments for AP.
Purpose of the Study:
- To review current research on calcium's role in AP pathogenesis.
- To assess the effectiveness of pharmacological interventions targeting calcium regulation in AP.
Main Methods:
- A comprehensive literature review of experimental and clinical studies was performed.
- Databases searched included PubMed, Scopus, and Google Scholar up to October 2025.
- Studies focused on calcium imbalance mechanisms and therapeutic agents in AP.
Main Results:
- Identified key targets: IP3 receptors, ryanodine receptors, SOC/CRAC channels, TMEM16A, PI3K/Akt, and calcineurin/NFAT pathways.
- Evaluated drugs like caffeine, dantrolene, DHA, Orai1 inhibitors, TMEM16A inhibitors, insulin, BAPTA-AM, cyclosporin A, tacrolimus, and miR-26a.
- These agents reduce calcium overload, suppress zymogen activation, stabilize mitochondria, and decrease inflammation.
Conclusions:
- Pharmacological correction of calcium homeostasis is a promising therapeutic strategy for AP.
- Further multicenter clinical trials are necessary to validate the safety and efficacy of these calcium-targeted treatments.
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