Akademik Veri Yönetim Sistemi
Peksöz R. (Yürütücü), Halıcı Z., Kutlu Z., Tavacı T., Özmen S., Atış V., et al.
Türkiye Sağlık Enstitüleri Başkanlığı (TÜSEB) Araştırma Projesi, 2023 - 2024
Sepsis is a heterogeneous clinical condition with immunological and physiological responses. Sepsis is the primary cause of hospital
death. Despite the successes in treatment today, sepsis still has a high mortality rate of 30-50%. Thus, Sepsis is a global public health
problem that poses a huge economic burden for patients and society.
Inflammation plays an important role in the formation of sepsis. Stokines such as TNF-a, IL-1β, IL 6 stimulate the inflammatory
response and provide the formation of reactive oxygen species (ROS). Excessive levels of ROS can damage biological macromolecules
such as DNA, proteins, and lipids, causing dysfunction of cells and tissues and exacerbating the immune response. Oxidative stress
develops in the organism due to the increase in the formation of free radicals and/or the deficiency in the antioxidant defense
system. In order to reduce free radical toxicity, antioxidant mechanisms develop a defense system against free radicals. In particular,
superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) are the leading enzymes. SOD plays an important role
in maintaining hemostasis by converting superoxide to oxygen and hydrogen peroxide, acting as an antioxidant. Elimination of ROS
leads to reduction of oxidative stress and regulation of expression of proinflammatory cytokines useful for the treatment of sepsis.
Avasopasem manganese (GC4419), a SOD mimetic, interrupts this process by converting superoxide to H2O2. In recent years, it is
seen that this dismutase mimetic drug has started to be used in studies as an effective therapeutic agent. With its manganese
superoxide scavenging activity, Avasopasem has a healing effect on mucositis caused by radiation in head and neck cancers. While it
has a protective effect on healthy tissue, it has an antitumoral effect. There are also studies on AVA on the current disease Covid-19.
Currently, there is no effective treatment for sepsis except supportive treatments such as fluid replacement and antibiotic therapy.
Thus, the possible curative effect of AVA gains great importance. In our planned study, in order to understand the severity of the
disease and to understand the damage to the tissues, the level of various inflammation markers will be examined and
histopathological and molecular examination of the tissues will be performed. Values before and after AVA in sepsis-induced mice
will be compared so that the possible effect of AVA will be evaluated. Lung is the first and most affected organ from sepsis. It is the
organ that best reflects the effects of sepsis in the body. Since lung tissue is used in most of the studies, we will examine the effect of
the drug on the lung tissue in our study.
Cecal ligation punctation (CLP), which is the most applied model in sepsis, is the method to be applied in this study. Medication will
be administered 1 hour after the CLP procedure. AVA will be administered intra-peritneally at 2.5 mg/kg, 5 mg/kg and 10 mg/kg
after sepsis. In the study, 5 groups will be made, 8 mice in each group. The control group (group 1), the sepsis group (group 2) and
the groups to which AVA will be administered (group 3,4,5). TNF-α, IL-1β, IL-6, catalase, myeloperoxidase (MPO) SOD, GSH levels in
lung tissue will be analyzed using Elisa and PCR method.
When all studies are completed, the effect of Avasopasem manganese on lung tissue in the polymicrobial sepsis model caused by
cecal ligation and puncture in mice will be explained biochemically, molecularly and histopathologically. In the light of this
information, we think that AVA may have significant effects on an important disease condition such as sepsis with its SOD mimetic
effect. We anticipate that important clinical studies will be conducted on sepsis in the future.