Elimination of intracellular Ca < sup > 2+ < /sup > overload by BAPTA ‑AM liposome nanoparticles: A promising treatment for acute pancreatitis

Int J Mol Med. 2024 Apr;53(4):34. doi: 10.3892/ijmm.2024.5358. Epub 2024 Feb 23.ABSTRACTCalcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‑AM), a cell‑permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra‑ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA‑AM‑loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. ...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Source Type: research