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kidney injury in liver cirrhosis: the role of cholestasis and of systemic inflammation in a contest of rat model liver cirrhosis induction by tetrachloride carbon inhalation

Questo Abstract è stato accettato come Poster.

Razionale

Acute kidney injury (AKI) is common in advanced liver dysfunction with cirrhosis. The most influential hypothesis is peripheral arterial vasodilation hypothesis with subsequent hemodynamic impairment, resulting in kidney disfunction. On the basis of recent knowledges, the need to revise the classical hypothesis was born, focusing the attention on choleric nephropathy(CN), a term describing renal disfunction in course of obstructive jaundice, and on inflammatory syndrome as responsible of advanced cirrhosis and systemic complications. We investigated an animal model of liver cirrhosis induced in rats.

Casistica e Metodi

Decompensated liver cirrhosis was induced by carbon tetrachloride inhalation for 13 weeks in 21 MaleWistarHan rats. Urine and plasma samples were collected during induction and Luminex analysis was carried out for biomarkers involved in inflammation (EPO, G-CSF, GM-CSF, GRO/KC, IFN-γ, IL1α-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17A, IL-18, M-CSF, MCP-1, MIP-1α, MIP-3α, RANTES, TNF-α,VEGF) and kidney injury (NGAL,Clauserine, Osteopontine,MCP1,KIM1,IL-18, B2microglobuline, cistatine-C, calbindine). Kidney histology was evaluated. Immunohistochemistry was used to study the main bile acids tubular transporters SLC10A1, P-Glycoprotein, Asbt, Mrp4 and Ost-β, also Caspase-3 and TLR-4 were analyzed

Risultati

At sacrifice, the livers were consistent with cirrhosis. Creatinine showed incremental mean values. Major histopathological features were not present. Luminex analysis showed that plasma cytokine had overlapping behaviors, suggesting a role in systemic inflammatory response in course of liver injury(Fig1); also urinary biomarkers showed typical behaviors(Fig2). Immunohistochemistry demonstrated variations between treated rats and control group about transporters analyzed(Fig3).

Conclusioni

We detected, for the first time, the pathogenesis of kidney injury in course of cirrhosis, in a rat model. We detected a chronological relationship between systemic inflammation r and kidney injury: we demonstrated a kidney involvement during a phase of compensated cirrhosis, hypothesizing a possible key role of bile acids in kidney disease in course of cirrhosis.

Angeletti A.(1), Donadei C.(1), Malvi D.(2), De Giovanni A.(2), Conti M.(3), Aldini R.(4), La Manna G.(1)
((1)Department of Experimental, Diagnostic, Specialty Medicine, Nephrology, Dialysis, and Renal Transplant Unit, S. Orsola University Hospital, Bologna, Italy ²Microbiology, DIMES, University of Bologna, Bologna, Italy; (2)‘‘F. Addarii’’ Institute of Oncology and Transplantation Pathology, Bologna University, Bologna, Italy; (3)National Institute of Biostructure and Biosystems (INBB), Interuniversity Consortium, Rome, Italy; (4)Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy)
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