title: Deoxyribonuclease partially ameliorates thioacetamide-induced hepatorenal injury.
abstract: Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation, exacerbating liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. This study analyzed the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals. Administration of deoxyribonuclease resulted in a mild, nonsignificant decrease in total plasma DNA and plasma DNA of mitochondrial origin but not of nuclear origin. This was accompanied by a decrease in bilirubin, creatinine, and blood urea nitrogen as markers of renal function. In conclusion, the study confirmed the hepatotoxic and nephrotoxic effect of thioacetamide. The associated increase in cell-free DNA seems to be involved in hepatorenal pathogenesis because treatment with deoxyribonuclease resulted in a partial prevention of hepatorenal injury. Further experiments will focus on the effects of long-term treatment with deoxyribonuclease in other clinically more relevant models. Clinical studies should test endogenous deoxyribonuclease activity as a potential risk determinant for kidney or liver failure.NEW & NOTEWORTHYThioacetamide-induced hepatorenal injury resulted in higher plasma cell-free DNA. Deoxyribonuclease decreased average cell-free DNA of mitochondrial origin but not nuclear origin. Deoxyribonuclease partially prevented hepatorenal injury in rats.
authors.affiliation: Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Vokálová
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lauková
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Čonka
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Melišková
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Borbélyová
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Janka
authors.initials: J
authors.lastname: Bábíčková
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: L'ubomíra
authors.initials: L
authors.lastname: Tóthová
authors.affiliation: Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.|Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Július
authors.initials: J
authors.lastname: Hodosy
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Barbora
authors.initials: B
authors.lastname: Vlková
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia; petercelec@gmail.com.|Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; and.|Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Celec
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000008:administration & dosage*; D006530:Hepatorenal Syndrome / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D016896:Treatment Outcome
chemical_list: D013853:Thioacetamide; D004247:DNA; D003851:Deoxyribonucleases
keywords: DNase; circulating nucleic acids; hepatorenal syndrome; liver failure; renal failure