Antioxidant and mitochondrial protective effects of silibinin in cold preservation-warm reperfusion liver injury.
OBJECTIVE
Silybum marianum (milk thistle) is a Mediterranean plant that has been used since Greco-Roman times to treat liver ailments. Silibinin, the most active hepatoprotective constituent of the plant's seed, possesses antioxidant and anti-inflammatory properties. We thus assessed its protective potential in liver transplantation injury.


METHODS
Rat livers were isolated and preserved during 24h at 4 degrees C in University of Wisconsin (UW) solution alone (control), UW containing 100 microM silibinin or UW containing vehicle (ethanol). Livers were then reperfused at 37 degrees C for 1h with Krebs-Henseleit solution supplemented with 20% erythrocytes.


RESULTS
Compared to control, cold preservation and warm reperfusion promoted lipid peroxidation (+40%) and superoxide anion generation (+147%), while attenuating reduced glutathione (-23%), mitochondrial ATP content (-57%) and respiratory control ratio (RCR; -37%). Preservation done in presence of silibinin improved parameters affected by preservation and reperfusion. In fact, silibinin promoted an increase of ATP and RCR by, respectively, 39 and 16% and decreased oxidative stress to values observed in livers never preserved nor perfused.


CONCLUSIONS
In conclusion, silibinin shows promise in protecting the liver from cold preservation/warm reperfusion damages. Moreover our study suggests that concepts of traditional medicine have the potential to be transposed successfully in the context of modern medical interventions such as liver transplantation surgery.
Département de Pharmacologie and Groupe d'étude des protéines membranaires, Université de Montréal, Montreal, Quebec, Canada.
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Ligeret
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Brault
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Vallerand
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Haddad
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Haddad
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008519:Medicine, Traditional; D020944:Silybum marianum / Q000737:chemistry*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D012639:Seeds; D000077385:Silybin; D012838:Silymarin / Q000302:isolation & purification / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014325:Tromethamine
D000975:Antioxidants; C074097:Krebs-Henseleit solution; D012838:Silymarin; D014325:Tromethamine; D013481:Superoxides; D000077385:Silybin; D000255:Adenosine Triphosphate; D005978:Glutathione; D005947:Glucose