Georgios Kyriakopoulos1, Alexandra K Tsaroucha1,2, Georgia Valsami3, Maria Lambropoulou4, Nikolaos Kostomitsopoulos5, Eirini Christodoulou3, Zacharias Kakazanis5, Constantinos Anagnostopoulos6, Christos Tsalikidis1, Constantinos E Simopoulos1,2,5. 1. a Postgraduate Program in Hepatobiliary/Pancreatic Surgery, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 2. b 2nd Department of Surgery and Laboratory of Experimental Surgery, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 3. c School of Health Sciences, Department of Pharmacy , National and Kapodistrian University of Athens , Greece. 4. d Laboratory of Histology-Embryology, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 5. e Department of Experimental Surgery , Bioresearch Foundation of the Academy of Athens , Athens , Greece. 6. f Laboratory of Biochemistry, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
Abstract
BACKGROUND: Remote kidney damage is a sequel of hepatic ischemia-reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury. MATERIAL AND METHODS: 63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 μL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals. RESULTS: Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001). CONCLUSION: Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.
BACKGROUND: Remote kidney damage is a sequel of hepatic ischemia-reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury. MATERIAL AND METHODS: 63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 μL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals. RESULTS: Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001). CONCLUSION: Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.
Entities:
Keywords:
M30; Renal damage; Silibinin; TNF-α; ischemia-reperfusion injury; rat
Authors: Georgios Kyriakopoulos; Georgia Valsami; Christos Tsalikidis; Michail Pitiakoudis; Alexandra K Tsaroucha Journal: Ann Med Surg (Lond) Date: 2020-11-26
Authors: Adamantios Michalinos; Alexandra K Tsaroucha; Maria Lambropoulou; Dimitrios Schizas; Georgia Valsami; Nikolaos Kostomitsopoulos; Michael S Pitiakoudis; Constantinos E Simopoulos Journal: Transl Gastroenterol Hepatol Date: 2020-01-05