Sepsis caused by infection is one of the most important problems of clinical medicine. This study aimed to determine the effect of Apilarnil (API), a bee product, on lipopolysaccharide (LPS) induced liver injury. In the study, 64 adult Sprague-Dawley rats were divided into eight groups; control, 0.2, 0.4 and 0.8 g / kg apilarnil (API) treated groups, LPS (30 mg / kg) group, LPS + 0.2, LPS + 0.4 and LPS + 0.8 g / kg API. At tissues obtained from rats, histopathological evaluation, biochemical analysis by ELISA (Catalase-CAT, malondialdehyde-MDA, superoxide dismutase-SOD, xanthine oxidase-XOD, and testican 1-TCN-1), immunohistochemical evaluation (Toll-like receptor 4 (TLR4), High Mobility Group Box Protein 1 (HMGB-1), nuclear factor kappa B (NF-κB), Tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6) and Inducible nitric oxide (iNOS)), TUNEL analysis to determine the number of apoptotic cells and Comet test as an indicator of DNA damage were performed. Histopathological examination revealed dilated blood vessels, inflammatory cell infiltration, and pyknotic nuclei damaged hepatocytes in the liver tissues of the LPS group. It was found that tissue damage was decreased significantly in LPS + API treatment groups compared to the LPS group. The number of TUNEL positive cells observed in the LPS group in liver samples increased compared to control and API-treated groups only (p < 0.05). The number of TUNEL positive cells showed a statistically significant decrease compared to the LPS group in the groups treated with LPS + API. LPS treatment increased MDA, XOD, and TCN 1 levels and decreased SOD and CAT levels; this effect was reversed in the groups treated with LPS + API. In the LPS group, DNA damage was significantly increased when compared with the LPS + API. LPS treatment increased expression of TLR4, HMGB-1, NF-κB, iNOS, TNF-α, IL-1β, IL-6; in the groups treated with LPS + API reduced this increase. In conclusion, apilarnil administered in rats may be thought to prevent LPS-induced liver damage by inhibiting the TLR4 / HMGB-1 / NF-κB signaling pathway.

Background: Sepsis is a serious clinical condition characterized by damage to the immune system as a result of an uncontrolled response to infection. Septic patients show complications such as fever, cardiovascular shock, and/or systemic organ failure. Acute organ failure formed in sepsis mostly affects the respiratory and cardiovascular systems. In sepsis, responses including pro-inflammatory and anti-inflammatory processes in addition to the Toll-Like Receptor 4 (TLR4) signals leading to the release of inflammatory mediators have been suggested to be fundamental pathways in the pathophysiology of sepsis. Purpose: In this context, unregulated levels of sepsis-associated inflammatory mediators may increase the risk of mortality. In sepsis, infection-induced pathogens lead to a systemic inflammatory response. These systemic responses may contribute to septic shock and organ dysfunction. In the unfavorable clinical course of sepsis, an uncontrolled inflammatory response is observed. Accordingly, the mechanism of inflammatory mediators such as cytokines and chemokines in sepsis might increase. Neurotransmitters and gene regulators affect inflammatory mediators and control the inflammatory response. In this review, we aimed to show the new therapeutic targets in sepsis treatment with current studies. New clinical implications targeting inflammatory mediators in high mortality affected by the uncontrolled inflammatory response in sepsis can contribute to the understanding of the symptoms.

Experimental and clinical studies of cardiac pathology associated with epilepsy have demonstrated an impact on the autonomic nervous system (ANS). However, the underlying molecular mechanism has not been fully elucidated. Molecular investigation of the neurotransmitters related receptor and ion channel directing ANS might help in understanding the associated mechanism. In this paper, we investigated the role of acetylcholine (ACh), which demonstrates both sympathetic and parasympathetic roles in targeted expression in terms of the relevant receptor and ion channel. Inwardly rectifying potassium (Kir) channels play a significant role in maintaining the resting membrane potential and controlling cell excitability and are prominently expressed in both the excitable and non-excitable tissues. The immunoreactivity of ACh-activated Kir3.1 channel and muscarinic ACh receptors (M2) in autonomic centers such as the brainstem, vagus nerve (VN) and atria of heart was confirmed by both histological staining and pathological tissue analysis. Significant upregulations of Kir3.1 and M2 receptors were observed in pentylenetetrazol (PTZ)-kindled epileptic rats for all related tissues investigated, whereas no pathological difference was observed. These findings provide proof-of-concept that changes in ACh-associated immunoreactivity might be linked to the ANS dysfunctions associated with epilepsy.