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Gene & Protein in Disease                               Dunaliella salina & myocardial ischemia-reperfusion injury



            cardiomyopathy to human health has grown . The first   injury through NRF2/KEAP1/antioxidant response
                                                 [1]
            principle of treatment is to restore blood supply to the   element (ARE) pathway activation . At the same time,
                                                                                           [14]
            ischemic  myocardium  as soon as  possible .  However,   the  inflammatory  damage  during  MIRI  should  not  be
                                                [2]
            reperfusion might further aggravate myocardial injury.   underestimated. The Janus kinase 2/signal transducer
            This is known as myocardial ischemia-reperfusion injury   and  activator  of transcription  3 (JAK2/STAT3) pathway
            (MIRI) . A  number of mechanisms are involved in it,   is involved in various cardiovascular complications,
                  [3]
            causing serious new dysfunction, including excessive   including cardiomyocyte apoptosis, endoplasmic reticulum
                                                                                                  [15]
            inflammatory response, calcium ion (Ca ) overload,   stress, oxidative stress, and inflammation . The rapid
                                                2+
            endoplasmic reticulum, and mitochondrial damage [4,5] .   activation of JAK2/STAT3 pathway after I/R enhances
            MIRI leads to an inflammatory response, resulting   the transcription of inflammatory cytokines, which are
            in inflammatory cell infiltration and accumulation of   closely related to myocardial damage [5,16] . The inhibition of
            proinflammatory factors . In addition, excessive oxidative   JAK2/STAT3 pathway could reduce inflammatory damage
                               [5]
                                                                                     [17]
            stress has also been reported to play an important role   in rats suffering from MIRI . The present study aimed at
            in MIRI. Previous research has identified the  oxidative   investigating the effect of D. salina on MIRI and the status
            stress theory as one of the main etiologies of MIRI, which   of KEAP1/NRF2 and JAK2/STAT3 signaling pathways
            usually originates in either the excessive production of   underlying D. salina against MIRI.
            reactive oxygen species (ROS) or the decline of scavenging
            capacity [6,7] .                                   2. Material and methods

              Dunaliella salina, a halophilic green microalgae, rich   2.1. Experimental animals
            in natural beta (β)-carotene, is considered an antioxidant   C57BL/6J mice  (male, 21–25  g)  were obtained from
            and anti-cancer compound, preventing night blindness,   Laboratory Animal Center of Henan University of Science
            delaying aging, and regulating immunity. In view of its   and Technology (Luoyang, China; license number: SCXK
            unique nutritional and functional components, D. salina   20190008). The mice  were randomly divided into three
            has the potential to be developed as a nutritional health food   groups (n = 8 per group) after 1 week of adaptive feeding:
                                                         [8]
            and authorized as additives for both humans and animals .   (i) Control group; (ii) I/R group; and (3) I/R + D. salina
            Hence, D. salina is considered a powerful antioxidant and   group (500 mg/kg). All mice in the I/R + D. salina group
            has excellent effect in preventing oxidative stress [9,10] . As   were given D. salina by gavage for 7 days consecutively,
            shown in mice, D. salina also has preventive effect on cornea   whereas the other two groups of mice were given saline
            injury induced by ultraviolet radiation, which may be due   in the same way. All mice were kept in a controlled
            to the increased activity of antioxidant defense system and   environment (temperature, 22 ± 2°C; humidity, 50 ± 5%;
            the inhibition of lipid peroxidation . A  study has also   12 h light/dark cycle). The mice had unrestricted access to
                                         [11]
            shown that  D.  salina could exert therapeutic potential   food and water.
            against  hepatic  encephalopathy  through  its  antioxidant,   The study was approved by the Animal Care and Ethics
            anti-inflammatory, and cytoprotective effects . Oral   Committee of Henan University of Science and Technology
                                                   [12]
            supplementation with D. salina has also shown to improve   (Luoyang, China) and was performed in accordance with
            cardiac dysfunction in obese rats . In addition, D. salina   the National Institutes of Health Guidelines for the Care
                                       [8]
            has shown to ameliorate heart dysfunction associated with   and Use of Laboratory Animals .
                                                                                        [18]
            aging in rats induced by D-galactose . Whether or not
                                          [10]
            D. salina could alleviate MIRI, the involved mechanism   2.2. Langendorff perfused heart model
            remains to be elucidated.
                                                               The mice were given intraperitoneal injection of ethyl
              The kelch-like ECH-associated protein 1 (KEAP1)/  urethane (1 g/kg) for anesthesia and heparin (500 IU/kg)
            nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling   for heparinization. The hearts were removed from the
            pathway is considered one of the most pivotal endogenous   thoracic cavity and attached on the Langendorff apparatus.
            antioxidative system . In brief, NRF2 and KEAP1 bind   Perfusion was maintained at a constant pressure with
                            [13]
            together in the cytoplasm physiologically. When stimulated,   warmed (37.5°C) perfusate, and the hearts were immersed
            NRF2 detaches from KEAP1, translocates to the nucleus,   in a water-jacketed temperature-controlled glass chamber
            and then promotes the expression of genes associated   at 37.5°C, so as to ensure normothermia throughout the
            with  antioxidant  activities,  such as  heme oxygenase-1   perfusion protocol. A latex balloon connected to the sensor
            (HO-1) and quinone oxidoreductase 1 (NQO1) . Recent   was inserted into the left ventricle of each heart through
                                                  [6]
            studies have shown that suppressing oxidative stress   left atrium incision. In the meantime, the heart rate, left
            response could ameliorate ischemia/reperfusion (I/R)   ventricular systolic pressure (LVSP), and electrocardiograph


            Volume 2 Issue 2 (2023)                         2                         https://doi.org/10.36922/gpd.387
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