Influência da curcumina na morfologia e função hepática durante a sepse

Abstract

Considered a serious public health problem, sepsis has a systemic character, rapid progression and is associated with high rates of morbidity and mortality. Despite recent advances in diagnosis and therapy, the evolution of the septic condition leads to injury and dysfunction in several organs, including the liver. The exacerbated immune response with excessive production of inflammatory mediators can damage and compromise the liver tissue, its functions and, consequently, the patient's improvement. Kupffer cells are directly involved in mediating such a response, as they play a great plasticity as a characteristic, they are able to activate in different profiles such as pro- inflammatory M1, with production of nitric oxide (NO) and / or anti-inflammatory M2, with arginase production. One of the promising forms of sepsis therapy is the use of natural substances, such as curcumin, as it has relevant anti-inflammatory and antioxidant functions, and studies indicate its ability to reduce the harmful effects caused by the inflammatory response in sepsis. Therefore, the objective of this work isto evaluate the effect of curcumin on the morphological and functional changes that occurred in the liver of mice submitted to experimental sepsis induced by ligation and perforation of the cecum (CLP). For this purpose, adult male C57Bl / 6 mice were used and divided into groups of animals: false-operated (SHAM), false-operated and treated with CUR (SHAM + CUR), animals subjected to sepsis (CLP) and animals submitted tosepsis and treated with CUR (CLP + CUR). The groups were divided into 24, 48, 72 and 120 hours. After each experimental period, the animals in the different groups were anesthetized and euthanized. Then, the liver was excised, processed and stained with hematoxylin and eosin (HE) for histological analysis and with PAS (periodic acid + Schiff's reactive) to assess glycogen deposits. For the assessment of liver function, the blood of the animals was collected without anticoagulants, the serum obtained was aliquoted, identified and stored in a freezer at - 80ºC until the measurement of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and globulin. In the histopathological evaluation of HE, it was possible to observe thatin the CLP + CUR 48h and 72h groups, cell lesions and steatosis decreased in relation to the 48h and 72h CLP subgroups. In the histopathological evaluation of PAS it was possible to observe moderate areas of glycogen in the CLP + CUR 72h and 120h groups, in relation to the CLP 72h and 120h subgroups. Biochemical markers of hepatocyte integrity (AST, ALT and AST / ALT), showed that curcumin reduced the enzymes of liver damage, preventing liver damage. In the evaluation of the biochemical parameters of hepatic synthesis and metabolism (Albumin, total proteins and Alb / Glob), it showed that curcumin stimulated the liver's synthesis functions, increasing protein production. It was possible to conclude that curcumin was able to reduce the appearance of lesions and damage to liver tissue during sepsis, partially preserving its integrity and functionality. It was also able to prevent the reduction of glycongen levels during sepsis.