The Effect of 30-minute Ischemia on the Levels of IL6, TNFα, NO, Glutathione and Lactic Acid in the Hepatic Tissue of Rats with Hepatic Steatosis

Sikalias, Nikolaos; Terzopoulou, Maria; Alexiou, Konstantinos; Mountzalia, Lamprini; Kamparoudi, Pagona; Zacharioudaki, Argyro; Papalois, Αpostolos; Karatzas, Theodore

doi:10.1007/s13126-019-0508-0

Cited by 1 publication

(2 citation statements)

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“…Same as group 3.1, but the donors were treated with an anti-IL-6 antibody (R&D Systems, Minneapolis, MN) at doses of 16.6 µg/kg (i.p. ), just after BD was induced ( 27 – 29 ), and reperfusion was allowed for 1 h.…”

Section: Methodsmentioning

confidence: 99%

“…steatosis has not been associated with inflammation (26). However, the Ob rats do show severe macrovesicular and microvesicular infiltration of fat into the hepatocytes (>60% steatosis) (27)(28)(29)(30)(31), whereas the Ln rats do not show any signs of steatosis (32). We performed all the procedures in accordance with the European Union regulations pertaining to animal experiments (Directive 86/ 609 EEC).…”

Section: Experimental Animalsmentioning

confidence: 99%

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NO–IL-6/10–IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats

Casillas-Ramírez,

Micó-Carnero,

Sánchez-González

et al. 2023

Front. Immunol.

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IntroductionBrain death (BD) and steatosis are both risk factors for organ dysfunction or failure in liver transplantation (LT)Material and methodsHere, we examine the role of interleukin 6 (IL- 6) and IL-10 in LT of both non-steatotic and steatotic liver recovered from donors after brain death (DBDs), as well as the molecular signaling pathways underlying the effects of such cytokines.ResultsBD reduced IL-6 levels only in nonsteatotic grafts, and diminished IL-10 levels only in steatotic ones. In both graft types, BD increased IL-1β, which was associated with hepatic inflammation and damage. IL-6 administration reduced IL-1β only in non-steatotic grafts and protected them against damage and inflammation. Concordantly, IL-1β inhibition via treatment with an IL-1 receptor antagonist caused the same benefits in non-steatotic grafts. Treatment with IL-10 decreased IL-1β only in steatotic grafts and reduced injury and inflammation specifically in this graft type. Blockading the IL-1β effects also reduced damage and inflammation in steatotic grafts. Also, blockade of IL-1β action diminished hepatic cAMP in both types of livers, and this was associated with a reduction in liver injury and inflammation, then pointing to IL-1β regulating cAMP generation under LT and BD conditions. Additionally, the involvement of nitric oxide (NO) in the effects of interleukins was evaluated. Pharmacological inhibition of NO in LT from DBDs prompted even more evident reductions of IL-6 or IL-10 in non-steatotic and steatotic grafts, respectively. This exacerbated the already high levels of IL-1β seen in LT from DBDs, causing worse damage and inflammation in both graft types. The administration of NO donors to non-steatotic grafts potentiated the beneficial effects of endogenous NO, since it increased IL-6 levels, and reduced IL-1β, inflammation, and damage. However, treatment with NO donors in steatotic grafts did not modify IL-10 or IL-1β levels, but induced more injurious effects tan the induction of BD alone, characterized by increased nitrotyrosine, lipid peroxidation, inflammation, and hepatic damage.ConclusionOur study thus highlights the specificity of new signaling pathways in LT from DBDs: NO–IL-6–IL-1β in non-steatotic livers and NO–IL-10–IL-1β in steatotic ones. This opens up new therapeutic targets that could be useful in clinical LT.

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Section: Methodsmentioning

confidence: 99%