Calcium-directed therapy in acute pancreatitis

Background. Acute pancreatitis (AP) is a common and potentially life-threatening disease with high rates of complications and mortality. One of its key pathogenic mechanisms is disruption of calcium homeostasis in pancreatic acinar cells. Excessive accumulation of cytosolic calcium triggers premature enzyme activation, mitochondrial dysfunction, oxidative stress, and systemic inflammation. Therefore, development of therapeutic strategies aimed at restoring intracellular calcium balance have emerged as a promising pathogenetic direction. Objective: 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 approaches to its pharmacological correction. Materials and methods. A literature review was conducted using PubMed, Scopus, and Google Scholar databases up to March 2025. The analysis included experimental (in vitro, in vivo) and clinical studies addressing the mechanisms of calcium imbalance in AP and the effects of different pharmacological agents on its correction. 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, 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 is a promising pathogenetic approach to the treatment of acute pancreatitis. Existing experimental and clinical data support the need for further multicenter studies to confirm the efficacy and safety of these methods in routine clinical practice.