Silibinin Improves TNF-α and M30 Expression and Histological Parameters in Rat Kidneys After Hepatic Ischemia/Reperfusion

• Published in: Journal of investigative surgery 2018-06, Vol.31 (3), p.201-209
• Main Authors: Kyriakopoulos, Georgios, Tsaroucha, Alexandra K, Valsami, Georgia, Lambropoulou, Maria, Kostomitsopoulos, Nikolaos, Christodoulou, Eirini, Kakazanis, Zacharias, Anagnostopoulos, Constantinos, Tsalikidis, Christos, Simopoulos, Constantinos E
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - pathology; Administration, Intravenous; Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Antioxidants - therapeutic use; Disease Models, Animal; Humans; ischemia-reperfusion injury; Keratin-18 - metabolism; Kidney - blood supply; Kidney - drug effects; Kidney - pathology; Liver - blood supply; Liver - pathology; m30; Male; Necrosis - drug therapy; Necrosis - etiology; rat; Rats; Rats, Wistar; renal damage; Reperfusion Injury - complications; silibinin; Silybin; Silybum marianum - chemistry; Silymarin - chemistry; Silymarin - pharmacology; Silymarin - therapeutic use; tnf-α; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0894-1939; 1521-0553
• DOI: 10.1080/08941939.2017.1308044

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. 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. 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). Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.