Ulus Travma Acil Cerrahi Derg. 2022; 28(12): 1667-1673 | DOI: 10.14744/tjtes.2021.00312

Effect of pheniramine maleate on rat skeletal muscle ischemia-reperfusion injury

Kubilay Erol¹, Eser Y. Sozmen², Ülkü Küçük³, Levent Kucuk^4
1Department of Orthopedics and Traumatology, Emot Hospital, Ýzmir-Türkiye
²Department of Medical Biochemistry, Ege University Faculty of Medicine, Ýzmir-Türkiye
³Department of Pathology, Tepecik Training and Research Hospital, Ýzmir-Türkiye
⁴Department of Orthopedics and Traumatology, Medicana International Hospital, Ýzmir-Türkiye

BACKGROUND: Skeletal muscle ischemia-reperfusion injury (IRI) is a common clinical problem encountered after tourniquet ap-plication or replantation. This study investigated the effect of pheniramine maleate (Ph), which is frequently used in clinical practice to reduce IRI, and compared its efficacy in IRI with N-acetylcysteine (NAC), a molecule that has been shown to be effective in IRI.
METHODS: Twenty-eight male Sprague–Dawley rats were randomly divided into four groups (sham, ischemia-reperfusion [IR], IR+Ph, IR+NAC; n=7 rats per group). Ischemia was induced in the lower right extremities of rats for 3 h using a femoral artery clamp and an elastic tourniquet. Ph and NAC were administered intraperitoneally 15 min before ischemia was terminated. At 24 h after reperfusion, levels of thiobarbituric acid reactive substance (TBARS), catalase (CAT), myeloperoxidase (MPO), superoxide dismutase (SOD), polyadenosine diphosphate ribose polymerase (PARP), and neutrophil infiltration were evaluated. Inducible nitric oxide syn-thase (iNOS) density in muscle tissue was evaluated by immunohistochemical methods after 1 week.
RESULTS: SOD, MPO, PARP, CAT, and TBARS levels in muscle tissue were significantly lower in the sham group compared with the other groups (p<0.001). All parameters except TBARS were lower in the NAC and Ph groups than in the IR group (p<0.001). Neu-trophil infiltration in the muscle tissue samples from the IR group was significantly increased compared with the NAC and Ph groups (p<0.05). iNOS staining was not observed in the sham and NAC groups.
CONCLUSION: Ph is effective at reducing experimental rat skeletal muscle IRI.

Keywords: Inducible nitric oxide synthase, ischemia-reperfusion, N-acetylcysteine, pheniramine maleate; skeletal muscle.

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Feniramin maleatýn sýçan iskelet kasýndaki iskemi reperfüzyon hasarýna etkisi

Kubilay Erol¹, Eser Y. Sozmen², Ülkü Küçük³, Levent Kucuk^4
1Emot Hastanesi, Ortopedi ve Travmatoloji Bölümü, Ýzmir
²Ege Üniversitesi Týp Fakültesi, Týbbi Biyokimya Anabilim Dalý, Ýzmir
³Tepecik Eðitim ve Araþtýrma Hastanesi, Patoloji Bölümü, Ýzmir
⁴Medicana International Hastanesi, Ortopedi ve Travmatoloji Bölümü, Ýzmir

AMAÇ: Ýskelet kasý iskemi reperfüzyon hasarý (ÝRH) turnike uygulamalarý ve replantasyon sonrasý görülen klinik bir problemdir. Bu çalýþmada, klinik pratikte sýk kullanýlan bir molekül olan feniramin maleatýn (Ph) ÝRH’ný azaltmadaki etkisinin belirlenmesi ve ÝRH’ný azaltmada etkinliði kanýtlanmýþ olan N- asetil sisteinle (NAC) karþýlaþtýrýlmasý amaçlanmýþtýr.
GEREÇ VE YÖNTEM: 28 adet Sprague-Dawley sýçan rastgele yediþerli dört gruba ayrýldý. Gruplar sham, iskemi-reperfüzyon (ÝR), ÝR + Ph, ÝR + NAC olarak belirlendi. Sýçanlarýn sað alt ekstremitesinde femoral arter klempi ve elastik turnike ile üç saat süreyle iskemi oluþturuldu. Ph ve NAC, iskemi bitiminden 15 dakika önce intraperitoneal uygulandý. Reperfüzyondan 24 saat sonra kas dokusunda, tiobarbiturik asitle reaksiyon veren maddeler (TBARS), katalaz (CAT), süperoksit dismutaz (SOD), miyeloperoksidaz (MPO), poli adenozin di fosfat riboz polimeraz (PARP), nötrofil infiltrasyonu ve bir hafta sonra iNOS monoklonal antikor pozitifliði deðerlendirildi.
BULGULAR: Sham grubunda kas dokusundaki MPO, TBARS, PARP, SOD, CAT düzeyleri diðer gruplara oranla belirgin olarak düþük bulundu (p<.001). MPO, PARP, SOD, CAT düzeyleri ÝR + Ph grubunda ve ÝR + NAC grubunda ÝR grubundan belirgin olarak düþük bulundu (p<.001). Nöt-rofil infiltrasyonu ÝR grubunda ÝR + NAC ve ÝR + Ph grubundan belirgin olarak yüksek bulundu (p<0.005). ÝRH azaltýlmasýnda Ph ve NAC’ýn etklili olduðu, ikisi arasýnda anlamlý fark olmadýðý bulundu.
TARTIÞMA: Feniramin maleat sýçan iskelet kasýnda oluþan ÝRH’nýn azaltýlmasýnda etkin bir moleküldür.

Anahtar Kelimeler: CAT, feniramin maleat, iNOS, iskemi reperfüzyon; SOD.

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