Therapeutic effect of thiocetam on the manifestations of ischemia-reperfusion complicated by massive blood loss and mechanical trauma
KeywordsIschemia reperfusion injury, oxidative stress, catalase, skeletal trauma, blood loss, liver, hemostatic tourniquet, treatment, antioxidants
Among the current medical and social problems, injuries and blood loss occupy a prominent place, causing stress on the antioxidant defenses. Hypoxia, which underlies the pathogenesis of the post-traumatic period of both diseases, leads to a significant imbalance in the work of internal organs. Scientists are increasingly attracted by the need to use a tourniquet or intraoperative ligatures, as reperfusion local and systemic damage develops. Antioxidants are considered a promising means of correction.
The aim of the study was to investigate the features of metabolic disorders in the liver in the early post-traumatic period on the background of the use of a tourniquet and the effectiveness of thiocetam correction.
Materials and methods. The experiment was perfomed on 130 white male rats (200-250 g), which were divided into 4 groups: control – the CG, the EG-1 – combination of limb ischemia-reperfusion (IR) with blood loss, the EG-2 – combination of limb IR with blood loss and mechanical trauma of the thigh; the EG-3 combination of limb IR, blood loss, mechanical injury and thiocetam administration. The Malonic dialdehide level catalase activity were estimated in the liver.
Results. The use of thiocetam, which is able to struggle against of ischemia and lipid peroxidation by reactivating antiradical enzymes: superoxide dismutase, catalase and glutathione peroxidase, had a positive effect on the state of antioxidant and prooxidant units in the organ, located far from the place of primary ischemia-reperfusion. If in the group of untrated animals (the EG-2, where massive blood loss was combined with a thigh fracture and the use of hemostatic tourniquet) in the early period, the MDA level exceeded the CG data in 5,4 times, and on the 7th and 14th days remained high – being higher on 2,1 times and on 2,7 times, then in the EG-3 (group of treated animals) on the 1st day the level of MDA exceeded the CG data in 4,3 times, but on the 7th and 14th days was higher by 90,5 % and 64 % respectively. The supportive effect of thiocetam on the activity of catalase in the liver was also noted. Thus, in EG-2 the level of antioxidant enzyme on the 1st day decreased by 71,7 %, and remained almost at this level throughout the all post-experimental period. As for the group of treated animals, the level of activity on the 1st day after the intervention decreased by 44,7%, and was so for almost the entire period. On the 14th day, it remained reduced compared to the CG by 35,1 %, while in EG-2 this index was lower compared to the CG by 70,5 %.
Conclusion. Having the positive effect of the introduction of thiocetam in the ischemic area, we can eventually add new complex, given the world experience, which would affect the development of the inflammatory response and the rheological properties of blood.
Inauen, W., Inauen, M., Suzuki, Granger, D. N. (1989). Mechanisms of cellular injury: potential sources of oxygen free radicals in ischemia/reperfusion. Microcirculation, Endothelium and Lymphatics. 5(3-5), 43-55.
Petukhov, E. B. (2009). Gomoreologicheskiye problemy pri khronicheskoy arterialnoy nedostatochnosti nizhnikh konechnostey [Homorheological problems in chronic arterial insufficiency of the lower extremities]. Angiologiya i sosudistaya khirurgiya. № 2(15, 13-19. [in Russian].
Flu, H., van der Hage, J. H., Knippenberg, B., Merkus, J. W., Hamming, J. F., Lardenoye, J. W. H. (2008). Tratment for peripheral arterial obstructive disease: An appraisal of the economic outcome of complications. Journal of vascular surgery. Vol. 48(2), 368-376.
Blaisdell, F. W. (2002). The pathophysiology of sceletal muscle ischemia and the reperfusion syndrome: a review. Cardiovascular surgery. Vol. 10(6, 620-630.
Rumyantseva, S. A. Oganov, R. G.. Stupin, V. A. (2013). Problemy i perspektivy korrektsii rpomezhutochnogo metabolizma u bolnykh s sosudistoy komorbidnostyu [Problems and Prospects for Correction of Intermediate Metabolism in Patients with Vascular Comorbidity]. Рациональная фармакотерапия в кардиологии. № 9(3), 316-322 [in Russian].
Kukaeva, E. A., Kukaeva, N. Iu. Andrianova, M. V. Paliulina, V. I. Mil’chakov (2003). Metabolicheskiye aspekty reperfuzionnogo sindroma u patsiyenta s khronicheskoy ishemiyey nizhnikh konechnostey posle khirurgicheskoy revaskulyarizatsii [Metabolic aspects of reperfusion sundrome in patient with chronic ischemia of the lower limbs after surgical revascularization]. // Patologicheskaia fiziologiia i experimentalnaia terapiia. Vol. 4-5(2), 25-27. [in Russian].
Nowak, K., Weih, S., Metzger, R., Albrecht, R. F. Post, S., Hohenberger, P., Gebhard, M. M., Danilov, S. M. (2007). Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo. American Journal of Physiology-Lung Cellular and Molecular Physiology. № 293(1), L162-L169.
Nanobashvili, J., Neumayer, C., Fuegl, A., Blumer, R., Prager, M., Sporn, E., Polterauer, P. Malinski, T., Huk I. (2003). Development of 'no-reflow' phenomenon in ischemia/reperfusion injury: failure of active vasomotility and not simply passive vasoconstriction. European Surgical Research Journal. № 35(5), 417-424
Sun, M. S., Jin, H., Sun, X., Huang, S., Zhang, F. L., Guo, Z. N., Yang Y. (2018). Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy. Oxidative Medicine and Cellular Longevity ;2018:3804979.
Zweier, J. L, Talukder, M. A. (2006). The role of oxidants and free radicals in reperfusion injury. Cardiovascular Research. № 70(2), 181-190.
Kolesova, O. E., Markin, A. A., Fedorova T. N. (1984). [Lipid peroxidation and methods for determining lipid peroxidation products in biological media]. Laboratory work. № 9, 540–546. [in Russian].
Korolyuk, V. A. Ivanova, L. I., Mayorova, I. G., Tokarev, V. E. (1988). [Method for determining catalase activity]. Laboratory work. № 1, 16-19. [in Russian].
Law of the Ministry of Health of Ukraine № 690
Volotovska, N. V. (2020). Porivnialna kharakterystyka aktyvnosti peroksydnoho okysnennia lipidiv ta antyoksydantnoho zakhystu v pechintsi shchura na tli eksperymenalnoho ishemichno-reperfuziinoho syndromu kintsivky [Comparative characteristics of lipid peroxidation activity and antioxidant protection in rat liver on the background of experimental ischemic-reperfusion syndrome of the limb]. Medychni perspectyvy. № 4 (25), 39-47. [in Ukrainian].
Liu, Y. L. Chen, Y. Shen, T. Tan, N. Xie, M. Luo, Z. Li, X. Xie (2016). Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation. Medical Science Monitor. № 22, 2035-2042.
Yasa, H., Yakut, N., Emrecan, B., Ergunes, K., Ortac, R., Karahan, N., Ozbek, Gurbuz A. (2008). Protective effects of levosimendan and iloprost on lung injury induced by limb ischemia-reperfusion: a rabbit model. Journal of Surgical Research. № 147(1), 138-142.
Lardot, C. F., Broeckaert, D., Lison, D., Buchet, J. P., Lauwerys, R. (1996). Exogenous catalase may potentiate mediated lung injury in the female Sprague-Dawley rat . Journal of toxicology and envoronmental health. – 1996. – № 47(6). – Р. 509-522.
Burkley, G. B. (1987). Pathophysiogy of free radical-mediated reperfusion injury. Journal of vascular surgery. Vol. 5(3), 512-517.
Skjeldal, S., Torvik, A., Nordsletten, L., Kirkeby, O. J., Grøgaard, B., Svindland, A., Reikerås, O. (1993). Local hypothermia during ischemia or reperfusion in skeletal muscles. Research in experimental medicine. № 193 (2), 73-80.
Ferrari, R., Andrade, C. F. (2015). Oxidative Stress and Lung Ischemia-Reperfusion Injury / // Oxidative Medicine and Cellular Longevity. 2015:590987
Skjeldal, S. A., Skjeldal, K., Hvaal, L., Nordsletten, L. (1994). Pentoxifylline reduces skeletal muscle necrosis after acute hindlimb ischemia in rats. European Surgical Research. Vol. 26 (2), 94–100.
Bolcal, C., Yildirim, V., Doganci, S., Sargin, M., Aydin, A., Eken, A., Ozal, E., Kuralay, E., Demirkilic, U., Tatar, H. (2007). Protective Effects of Antioxidant Medications on Limb Ischemia Reperfusion Injury. Journal of Surgical Research. Vol. 139(2), 274–279.
Kirişçi, M., Güneri, B., Seyithanoğlu, M., Kazancı, Ü., Doğaner, A., Güneş, H. 2020). The protective effects of lycopene on ischemia/reperfusion injury in rat hind limb muscle model. Ulus Travma Acil Cerrahi Derg. Vol. 26(3), 351-360
Takhtfooladi, H. A., Hesaraki, S., Razmara, F., Takhtfooladi, M. A., Hajizadeh, H. (2016). Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury. Jornal Brasileiro de Pneumologi. Vol. 42(1), 9–14.
Gökhan, Ö. (2012). Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion. Turkish Journal of Thoracic and Cardiovascular Surgery. Vol. 20(3), 577-583.
How to Cite
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Number of views and downloads: 152
Number of citations: 0