Effects of Hydrogen-rich Water on the PI3K/AKT Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury

Abstract

Background: The effects of hydrogen-rich water on PI3K/AKT-mediated apoptosis were studied in rats subjected to myocardial ischemia-reperfusion injury (MIRI). Methdos: Sixty rats were divided randomly into a hydrogen-rich water group and a control group. The hearts were removed and fixed in a Langendorff device. Hearts from the control group were perfused with K-R solution, and hearts from the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The two treatment groups were then divided randomly into pre-ischemic period, ischemic period and reperfusion period groups(10 rats per group), which were subjected to reverse perfusion for 10 min, normal treatment for 20 min, and reperfusion for 20 min, respectively. The mRNA and protein expression levels of PI3K, AKT, p-AKT, FoxO1, Bim and Caspase-3 in each group were detected by RT-qPCR, immunohistochemistry (IHC) and Western blotting. Caspase-3 activity was detected by spectrophotometry. Results: Among the hydrogen-rich water group, the PI3K/AKT signaling pathway was significantly activated, and FoxO1, Bim, and Caspase-3 mRNA and protein levels were significantly decreased in ischemia-reperfusion subgroup compared with the preischemic and ischemic subgroups. In the ischemia-reperfusion hydrogen-rich water group, PI3K, AKT and p-AKT mRNA and protein expression levels were increased while the FoxO1, Bim and Caspase-3 expression levels were significantly decreased compared with those in the corresponding control group (p<0.05). Conclusion: Hydrogen-rich water can activate the PI3K/AKT signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts, and inhibit cardiomyocyte apoptosis.

Hydrogen: A Novel Option in Human Disease Treatment

“…Additionally, Terasaki and colleagues reported that H 2 can downregulate the gene expression of proapoptotic Bax and inhibit its translocation to mitochondria by an unknown mechanism [ 39 ]. H 2 can also inhibit apoptosis by activating the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathways in rats with myocardial ischemia-reperfusion injury (MIRI) [ 40 , 41 ], as well as downregulating the p38 MAPK signaling pathway in rat models with lipopolysaccharide- (LPS-) induced acute lung dysfunction [ 42 ] and cerebral ischemia-reperfusion injury (CIRI) [ 43 ]. Interestingly, Wang et al recently discovered that H 2 inhibited the growth, migration, and invasion of the A549 and H1975 lung cancer cell lines and promoted cell apoptosis, suggesting that H 2 might play crucial roles in the treatment of lung cancer [ 44 ].…”

“…In addition to treating atherosclerosis, H 2 reduces MIRI, which refers to a heart lesion that develops upon the resumption of the flow of oxygen-rich blood after a period of ischemia and which usually occurs during acute myocardial infarction or open-heart surgery [ 40 , 90 ]. A recent series of studies by Li et al found that HW inhibited cardiomyocyte apoptosis by activating the PI3K/AKT and JAK2-STAT3 signaling pathways and can also reduce the level of oxidative stress in myocardial tissue by upregulating the expression of the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway, which alleviated I/R injury in isolated rat hearts [ 39 , 40 , 91 ]. Other studies demonstrated that intraperitoneal injection of HW before reperfusion significantly decreased the concentration of malondialdehyde (MDA) and infarct size, as well as reducing myocardial 8-OHdG and the levels of TNF- α and IL-1 β in an area at risk zones [ 92 , 93 ].…”

PEDF and 34‐mer peptide inhibit cardiac microvascular endothelial cell ferroptosis via Nrf2/HO‐1 signalling in myocardial ischemia‐reperfusion injury

“…Reperfusion therapy, while crucial in ischemic heart disease (IHD) treatment, paradoxically contributes to MIRI in clinical therapy. 20,21 More recently, several studies indicated that limiting reperfusion injury prevents microvascular obstruction and reduces final infarct size, thereby lowering the probability of heart failure events and improving quality of life in AMI patients. 22 Our study delves into the relationship between PEDF, Nrf2 and ferroptosis, investigating their potential therapeutic roles in MIRI.…”

Systems pharmacology dissection of the anti-myocardial ischemia-reperfusion injury mechanism for Ganjiang Fuzi decoction

“…First, it phosphorylated the PIP2 for the production of PIP3, subsequently, it activated the Akt, activating the downstream targets and promoting apoptosis [35,36]. Li et al discovered that the hydrogen-rich water activated the PI3K-Akt signaling pathway, reduced the ischemia/reperfusion injury of the isolated rat hearts, and inhibited the apoptosis of the myocardial cells [37]. The TNF was found to bind to two types of receptors, TNFR1 and the TNFR2.…”