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

Fu,Zailin; Wang,Dingsheng; Zheng,Caiyun; Xie,Minghua; Chen,Yifang; Zhou,Yi; Huang,Yan; Song,Ying; Hong,Weiyong

doi:10.3892/ijmm.2024.5358

Elimination of intracellular Ca²⁺ overload by BAPTA‑AM liposome nanoparticles: A promising treatment for acute pancreatitis

Authors:
- Zailin Fu
- Dingsheng Wang
- Caiyun Zheng
- Minghua Xie
- Yifang Chen
- Yi Zhou
- Yan Huang
- Ying Song
- Weiyong Hong
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Affiliations: Department of Pharmacy, Linping Branch, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China, Department of Pharmacy, Linping Branch, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China, Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310000, P.R. China, Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310000, P.R. China, Department of Pharmacy, Municipal Hospital Affiliated to Taizhou University, Taizhou, Zhejiang 318000, P.R. China
Published online on: February 16, 2024 https://doi.org/10.3892/ijmm.2024.5358
Article Number: 34
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Calcium 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%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF‑α, IL‑6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca²⁺ overload in patients with AP.

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