Phosphocreatine disodium salt is a crucial energy store in tissues with high, fluctuating energy demands like muscle and brain [1]. Phosphocreatine disodium salt interacts with phospholipids to influence membrane properties and exert membrane protection [2]. Phosphocreatine disodium salt is an effective and safe cardioprotective agent, which has been widely used in different animal models to protect the heart from intraoperative injury and improve cardiac function[3].
In vitro, Phosphocreatine disodium salt pretreatment at 20mM for 2 hours significantly attenuated methylglyoxal (MGO)-induced PC12 cell damage and inhibited MGO-induced apoptosis[4]. Pretreatment of NRK-52E cells with 40mM Phosphocreatine disodium salt for 4 hours significantly restored the viability of MGO-injured NRK-52E cells, resulting in a significant decrease in MDA levels, a significant increase in GSH and SOD levels, and inhibition of intracellular ROS production[5]. Pretreatment of H9C2 cells with 20mM Phosphocreatine disodium salt for 2h attenuated the cytotoxicity of recovered MGO, significantly increased Bcl-2 expression, decreased Bax expression, and improved mitochondrial respiration[6].
In vivo, a single dose of Phosphocreatine disodium salt (400mg/kg) administered intravenously 30min before cerebral ischemia-reperfusion (IR) can protect neurological function, reduce infarct volume, and brain cell apoptosis in rats 72 hours after focal cerebral IR[7]. Daily oral administration of Phosphocreatine disodium salt in drinking water (78mM) for one week reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice[8].
References:
[1] Guimarães-Ferreira L. Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles[J]. Einstein (Sao Paulo), 2014, 12: 126-131.
[2] Tokarska-Schlattner M, Epand R F, Meiler F, et al. Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects[J]. 2012.
[3] Xi H, Zhang A, Han G, et al. Pharmacokinetics and hemorheology of phosphocreatine and creatine in rabbits: A directly comparative study between parent drug and active metabolite[J]. European Journal of Pharmaceutical Sciences, 2019, 138: 105033.
[4] Li H, Tang Z, Chu P, et al. Neuroprotective effect of phosphocreatine on oxidative stress and mitochondrial dysfunction induced apoptosis in vitro and in vivo: Involvement of dual PI3K/Akt and Nrf2/HO-1 pathways[J]. Free Radical Biology and Medicine, 2018, 120: 228-238.
[5] Shopit A, Niu M, Wang H, et al. Protection of diabetes-induced kidney injury by phosphocreatine via the regulation of ERK/Nrf2/HO-1 signaling pathway[J]. Life Sciences, 2020, 242: 117248.
[6] Qaed E, Wang J, Almoiliqy M, et al. Phosphocreatine improves cardiac dysfunction by normalizing mitochondrial respiratory function through JAK2/STAT3 signaling pathway in vivo and in vitro[J]. Oxidative medicine and cellular longevity, 2019, 2019(1): 6521218.
[7] Li T, Wang N, Zhao M. Neuroprotective effect of phosphocreatine on focal cerebral ischemia‐reperfusion injury[J]. BioMed Research International, 2012, 2012(1): 168756.
[8] Bhagavatula G, Worledge C S, Schaepe C, et al. Phosphocreatine rescues intestinal epithelial metabolic dysfunction related to creatine kinase loss and is protective in murine colitis[J]. Cellular and Molecular Gastroenterology and Hepatology, 2025: 101557.