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Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. Background: Severe hyperbilirubinemia can cause permanent neurological damage here particular in neonates, whereas mildly To What Extent To Different Concentrations Of https://amazonia.fiocruz.br/scdp/blog/woman-in-black-character-quotes/the-policies-of-eisenhower-s-vietnam-and.php bilirubin protects from various oxidative stress-mediated diseases. Concentrationd present work aimed to establish the intracellular unconjugated bilirubin concentrations iUCB thresholds differentiating between anti- and pro-oxidant effects. Unconjugated bilirubin UCB is the final product of the heme catabolic pathway in the intravascular compartment.

UCB is produced by the activity of heme oxygenase HMOXan enzyme that splits the Exyent ring of heme into biliverdin, carbon monoxide, and ferrous iron. Subsequently, biliverdin is reduced by biliverdin reductase BLVR into UCB, which is transported in blood tightly bound to serum albumin before uptake by the hepatocyte.

Only less than 0. The Bf fraction determines the biological activities of bilirubin [ 1 ]. UCB can diffuse into any cell [ 23 ] and although being a potent antioxidant at low concentrations, it is toxic at high concentrations. Hence, all cells must maintain the intracellular concentration of UCB below toxic thresholds.

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This is regulated by its intracellular metabolism conjugation and oxidation as well as export out of the cells. UCB export is another mechanism used by hepatic and non-hepatic cells to prevent their intracellular accumulation.

Under physiological conditions, these efflux pumps are expressed in organs involved in the elimination of endo- and xeno-biotics, such as the liver and the kidney, and in epithelial tissues that protect the organs from the entry of xenobiotics, like the small intestine, testes, placenta, and blood—brain barrier BBB [ 14 ]. Hence, bilirubin behavior in a human body has two faces, similar to Janus Bifrons, a Roman god. Cells use multiple systems to protect against reactive oxygen species ROS. Enzymes with antioxidant actions include catalase and superoxide dismutase that together convert superoxide to water. Glutathione GSH is regarded as the principal endogenous intracellular small molecule antioxidant cytoprotectant. Studies on cells depleted of GSH or bilirubin indicate that bilirubin is of comparable, or greater, importance to GSH in cytoprotection [ 18 ] since bilirubin is one of To What Extent To Different Concentrations Of most abundant endogenous antioxidants in mammalian tissues [ 19 ].

Among extensive series of antioxidants, bilirubin has the most potent superoxide and peroxide radical scavenger activities [ 20 ].

UBC Theses and Dissertations

The potent physiologic antioxidant actions of bilirubin are further amplified by the oxidation of bilirubin to biliverdin and then recycled by biliverdin reductase back to bilirubin [ 18 ]. Nevertheless, it seems that each cell type and tissue may have a different bilirubin threshold switching between beneficial and toxic effects.

A similar dual effect was reported in the primary cultures of oligodendrocytes, showing protective effects at UCB concentration from 0. However, the exact concentration thresholds between anti- and Diffeerent effects of bilirubin remain undefined and need further investigation [ 23 ].

Thus, in the present work, we performed an in vitro study using different human and murine cell lines exposed to increasing concentrations To What Extent To Different Concentrations Of UCB, and correlated the intracellular unconjugated bilirubin concentrations with cytotoxic, antioxidant and prooxidant effects.

The four cell lines were exposed to a dose-dependent UCB treatment for 24 h and cytotoxicity was assessed by the propidium iodide PI test Conncentrations 1. The effect of unconjugated bilirubin UCB treatment on cell viability.

The cell lines were exposed to the increasing UCB concentration from 0. The percentage of dead cells was calculated as Or proportion of fluorescence intensity of dead cells to that of total cells. UCB cytotoxicity showed three different levels of susceptibility among the cell lines. HepG2 cell line was less sensitive, while the neuronal cells appeared the most sensitive. HK2 and H5V showed an intermediate dose-dependent cytotoxicity behavior. The first significant increase in dead cells was detected at UCB concentrations of 3.

No changes were observed in HepG2. The effect of UCB on the metabolic activity of studied cells. The cell lines were exposed to the increasing UCB concentrations from 0. All four cell lines were exposed for 24 h to increasing UCB concentrations, and then the intracellular bilirubin concentrations were determined Table 1.]