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Global Translational Medicine                                         Hesperetin alleviates pulmonary injury



            increased TNF-α expression. 26,32  In the current study,   generally observed with multiple traumas, while this study
            hesperetin attenuated pulmonary TNF-α expression, in   created a PC model manifesting only a unilateral trauma.
            addition to obstructing aggregation of inflammatory cells   In addition, all animals used in this research were male,
            and PML as well as reducing IL-1β and IL-6 levels.  so there is no information regarding how females would
              iNOS is one of the enzymes that produce nitric   react to this treatment model. Furthermore, the vital signs
            oxide (NO) related to the inflammatory process and   and oxygenation status of the animals were not determined
            have significant biological activity in the lungs.  In   during or at the end of the study. This study also did not
                                                      33
            healthy lung tissue, iNOS is not expressed, but increased   perform any analysis of bronchoalveolar fluids.
            iNOS expression in the inflammation and tissue injury   5. Conclusion
            processes has been reported in many studies. 34-36
            Reaction of NO with superoxide anions, especially   The pathological manifestations of unilateral PC induced
            reactive  oxygen  species  (ROS),  produces  peroxynitrite   with blunt chest trauma in rat model include pulmonary
            which causes apoptosis and tissue injury in the lungs.    edema and hemorrhage, interalveolar septum thickening,
                                                         37
            In the present study, consistent with previous studies of   and pulmonary inflammation.  Besides,  PC is associated
            the PC model, 38,39  rats that had been induced with PC   with increased levels of TNF-α in lung tissues and IL-1 and
            exhibited significantly increased expression of iNOS, as   IL-6 expressions in serum. This study also determined that
            compared to the control group. Previous experimental   increased MDA level is a lipid peroxidation marker in PC.
            studies demonstrated that iNOS inhibitors can prevent   To alleviate the PC injury caused by blunt chest trauma,
            tissue injury and suppress inflammatory response.  In   hesperetin stands out as a potential cure by inhibiting
                                                       40
            the present study, we detected lower iNOS expression   the synthesis of TNF-α and iNOS in lung tissues and
            in the PC + hesperetin group, along with reduced   pro-inflammatory cytokine production in serum, as well
            histopathological injury score as well as levels of   as ameliorating tissue damage, pulmonary edema, and
            TNF-α, IL-1β, and IL-6, all of which are compatible   inflammation.
            with results observed in the previous studies. It has been
            reported that the beneficial effects of hesperetin are   Acknowledgments
            attributable to its ability to suppress pro-inflammatory   None.
            cytokine production and prevent activation of NF-κβ
            transcription factor, as shown in  in vivo and  in vitro   Funding
            experimental studies of ulcerative colitis, hepatitis, LPS-
            induced ALI, and neuroinflammation. 41-44          None.
              Determining MDA levels, the end product of lipid   Conflict of interest
            peroxidation,  is  one of  the most commonly  used  and   The authors declare that they have no competing interests.
            reliable methods to assess lipid oxidation in tissue.
                                                         45
            Compatible with the findings of the present study, high   Author contributions
            MDA levels  in the PC model  induced by blunt chest
            trauma have also been reported elsewhere. 46-48  In this   Conceptualization: Serkan Kaya, İhsan Karaboğa
            study, we found that hesperetin significantly reduced   Formal analysis: Serkan Kaya, İhsan Karaboğa
            MDA level in the PC + hesperetin group compared to   Investigation: Serkan Kaya, İhsan Karaboğa, Yasin Duran,
            the PC group. Increasing MDA levels in a doxorubicin-  Fatin Rüştü Polat
            induced oxidative stress model  and in a lead acetate-  Methodology: İhsan Karaboğa, Yasin Duran, Zeynep
                                      49
            induced oxidative stress model  were reported to      Fidanol Erboğa, Elif Polat
                                        14
            significantly reduce with administration of hesperetin.   Writing – original draft: İhsan Karaboğa
            Similarly, in an LPS-induced ALI model, hesperetin   Writing – review & editing: All authors
            administration has been found to lower MDA level.
                                                         49
            These findings obtained in different experimental studies   Ethics approval and consent to participate
            showed that hesperetin administration prevents lipid   All applications in this experimental study were approved
            peroxidation.                                      by Tekirdag Namık Kemal University Experimental

              Several limitations of this study should be      Animals Local Ethics Committee (2018-T115).
            acknowledged. The PC model that was induced using   Consent for publication
            blunt chest trauma may not fully mimic the clinical tableau
            of the human disease. PC due to blunt chest trauma is   Not applicable.


            Volume 3 Issue 2 (2024)                         6                               doi: 10.36922/gtm.2568
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