TNF-a-dependent inflammatory liver

Melgert et al. studied the delivery of the corticosteroid dexamethasone to fibrotic livers [240], Dexamethasone has more potent and broader anti-inflammatory effects compared with naproxen. It inhibits the release of inflammatory mediators like TNF-a, IFN-y, and IL-6 and acts as an NFkB inhibitor [241, 242], Dexamethasone coupled to albumin (Dexa-HSA) was specifically taken up by sinusoidal cells in fibrotic rat livers, whereas dexamethasone itself was mainly taken up by hepatocytes. In vivo, Dexa-HSA promoted survival in endotoxin-induced liver inflammation in rats [240], In vitro, anti-inflammatory effects of the conjugate were measured in endotoxin-challenged liver slices. Dexa-HSA inhibited the release of nitric oxide and TNF-a in a dose-dependent manner (Melgert et al. unpublished data). To further enhance the delivery to KC at present dexamethasone is coupled to manHSA, and this conjugate is studied with respect to the pharmacokinetic profile and pharmacotherapeutic effects in fibrotic rats. 

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