Molecular Pathogenicity of Wild-Endotoxin Derived from Burned Patient's Skin and Proposed Effectiveness of Calcium Channel Inhibitors/Yanik Hasta Cildi Kaynakli Dogal Endotoksinin Molekuler Patojenitesinin Degerlendirilmesi ve Kalsiyum Kanal Blokerlerinin Olasi Etkinligi

Objective: Hepatic tissues of different patients exposed to systemic bacterial endotoxins are at risk of exposure to socalled lipopolysaccharide (LPS)-unfolded protein response (UPR)- calcium overload-gene splicing (LUCOGS). The essential workings mechanism of LUCOGS and their association with each other to start sepsis-related processes are not elucidated completely. This study aims to unravel the correlation between hepatic gene-splicing and the UPR machinery, in vivo. Methods: LPS was extracted from the patients' burned wounds after Pseudomonas aeruginosa isolation (hLPS), with informed consent. The male c57/BL6 mice were divided into six groups: 1. negative control (received sterile pyrogen-free normal saline); 2. positive control received tunicamycin; 3. hLPS (3 mg/kg/intraperitoneal); 4. hLPS+ dantrolene sodium (calcium channel inhibitor, CCI1) (A); 5. hLPS+2-aminomethyl phenyl borinate (1 mg/kg) (CCI2) (B); and 6. combined treatment with hLPS+CCI1/CCI2 (C). Subsequently, mice livers were extracted to evaluate XBP-1 splicing as a marker of the adaptive UPR activation after 2, 8, and 24 hrs. Results: Compared to the hLPS group, all three CCIs combined with hLPS exhibited a significant increase in the number of XBP-1 splicing. Compared to controls, Group C showed a maximum increase in the number of XBP-1 splicing after 8 and 24 hrs. Conclusions: Our results indicated that a combination of both CCIs could prevent the pro-inflammatory activation induced by hLPS, via UPR gene-splicing modifications. A new recipe of two types CCIs would potentially prevent the [Ca.sup.+2] overload intercellular after induced-endotoxemia. Prescription of both CCIs had higher effectiveness than separately to inhibit (pro-) inflammatory processes and could be considered a new strategy to appropriately manage and prevent both LUCOGS in systemic blood circulation and organ shutdown. The effectiveness of the new formula needs complementary studies to further clarify the introduced association mechanism, in vivo. Keywords: Endotoxin, burned skin, inflammation, liver, calcium channel inhibitors Amac: Sistemik bakteriyel endotoksin maruziyeti hepatik dokularda LUCOGS ("lipopolysaccharide (LPS)-unfolded protein response (UPR)- calcium overload-gene splicing") acisindan risk olusturmaktadir. LUCOGS mekanizmasi ve sepsisle iliskili sureci baslatmak uzere birbirleriyle etkilesimi tam olarak aciga kavusmamistir. Bu in vivo calisma, hepatik ucbirlestirme ve UPR arasindaki iliskinin aydin