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. Thioacetamide-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.

Fagonia indica Repairs Hepatic Damage through Expression Regulation of Toll-Like Receptors in a Liver Injury Model

“…Serum biochemistry is an important parameter for the diagnosis of liver diseases and for the assessment of the degree of liver damage [ 57 ]. Plasma levels of liver enzymes such as ALT, AST, and ALP, which are known hallmarks of TAA toxicity, are increased [ 58 , 59 ]. Similar results were observed in the present study where the TAA group showed considerable elevations in serum levels of ALT, AST, ALP, total proteins, and globulin compared to the control in accordance with previous findings [ 60 ].…”

Deoxyribonucleases and Their Applications in Biomedicine

“…Positive outcomes from clinical studies led to Food and Drug Administration (FDA) approval and wide use of DNase I for this treatment [113][114][115]. [130] Acute kidney injury rats intraperitoneal 0.1 mg/kg positive [131] Acute liver injury rats intravenous 10 mg/kg positive [132] Ischemic-reperfusion syndrome mice intraperitoneal intravenous 50 µg, 2 times 10 µg, 1 time positive [133] Empyema thoracis humans intrapleural 2.5 mg (1-2 times) positive [134] A similar effect of DNase was also seen in other respiratory diseases. Simpson et al collected the pus from patients with surgically drained soft tissue abscesses and with empyema thoracis and studied the effects of streptokinase and DNase [135].…”

Sex, Age, and Bodyweight as Determinants of Extracellular DNA in the Plasma of Mice: A Cross-Sectional Study

“…EcDNA is also a therapeutic target. In several diseases, it has been shown that ecDNA leads to inflammation and a release of more ecDNA—this vicious circle can be stopped by the removal of ecDNA, as shown for sepsis [9], hepatorenal injury [10], and metabolic syndrome [11,12].…”