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Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.
Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.
Human zoonotic visceral leishmaniasis (ZVL) and canine leishmaniasis (CanL) constitute a major public and veterinary health concern and are both caused by the infection with the protozoan parasite Leishmania infantum. One of the main target organs in CanL is the liver. This complex organ, composed of various highly specialized cell types, has garnered significant attention from the scientific community as a crucial player in innate immune functions. In the context of CanL, liver infection by parasites and the host immune response generated strongly influence the disease outcome. Thus, taking advantage of a co-culture system involving canine hepatocytes and L. infantum-infected autologous Kupffer cells (KCs), allowing cell-to-cell interaction, the current report aims to shed light on the hepatocyte-KCs immune interaction. The co-culture of infected KCs with hepatocytes revealed a vital role of these cells in the activation of a local immune response against L. infantum parasites. Although KCs alone can be immunologically silenced by L. infantum infection, the cell-to-cell interaction with hepatocytes in co-culture can lead to local immune activation. In co-culture it was observed gene expression increased the number of innate immune receptors, specifically cell membrane TLR2 and cytoplasmatic NOD1 along with high TNF-α generation. Altogether, these results suggest that the immune response generated in co-culture could induce the recruitment of other circulating cells to contain and contribute to the resolution of the infection in the liver. This work also enhances our understanding of the liver as a vital organ in innate immunity within the context of CanL.
Liver diseases cause about 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of this number. The cytokine and chemokine balance determines outcomes of immune response. Many cytokines are involved in progression and control of various liver diseases via regulation of cellular activity. Our aim was to assess the level of circulating cytokines and chemokines depending on the stage of fibrosis in children with chronic liver diseases. 51 children with chronic liver diseases were examined (32 children with autoimmune hepatitis, 12 children with Wilson’s disease, 5 children with Gaucher disease and 2 children with glycogen storage disease). All children were assessed for the stage of liver fibrosis (AF) using METAVIR scale (FibroScan F502). The contents of circulating serum cytokines, chemokines, growth factors and angiogenesis was determined by the MILLIPLEX® Human Cytokine/Chemokine/Growth Factor Panel A Magnetic Bead Panel, an immunoassay based on Luminex® technology. Statistical evaluation was carried out using the program “Statistica 10.0”. The levels of EGF, Fractalkine, IFNá, IL-10 and MIG increased significantly from F0 stage to F4 stage. A significant decrease from stage F0 to stage F4 was revealed for eotaxin, IL-5, IL-8, IL-17A. Some cytokines were characterized by nonlinear dynamics: the concentrations of IL-4 and MDC increased significantly from the F0 stage to the F2-3 stage, and then decreased to the F4 stage; the level of IL-18 showed a significant decrease by stage F2-3 relative to F0, then being significantly increased by stage F4. The level of TNFáwas increased at all stages of liver fibrosis and reached its maximum values at stage F2-3 of AF. Our data confirm the significant role of cytokines and chemokines in the pathogenesis of chronic liver diseases. The identified changes in circulating cytokines in the blood serum in children with CKD, depending on the stage of fibrosis, are characterized by differently directed disturbances thus presuming involvement of both pro- and anti-inflammatory mechanisms in the immunopathological process in the course of liver fibrosis formation. Further research is required in order to study the participation of cytokines and chemokines in formation of liver fibrosis for development of targeted therapy for liver diseases.
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