Erythropoietin inhibits liver gelatinases during galactosamine-induced hepatic damage in rats

• Published in: Pharmacological reports Vol. 61; no. 5; pp. 917 - 923
• Main Authors: Mądro, Agnieszka, Kurzepa, Jacek, Czechowska, Grażyna, Słomka, Maria, Celiński, Krzysztof, Szymonik-Lesiuk, Stanisława
• Format: Journal Article
• Language: English
• Published: Cham Elsevier Urban & Partner Sp. z o.o 01.09.2009; Springer International Publishing
• Subjects: Animals; Disease Models, Animal; Drug Administration Schedule; Drug Safety and Pharmacovigilance; erythropoietin; Erythropoietin - administration & dosage; Erythropoietin - pharmacology; Galactosamine; gelatinases; liver; Liver Diseases - physiopathology; Liver Diseases - prevention & control; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; MMP-2; MMP-9; Pharmacotherapy; Pharmacy; Protective Agents - administration & dosage; Protective Agents - pharmacology; Rats; Rats, Wistar; galactosamine; MMP-2; liver; rats; gelatinases; MMP-9; erythropoietin
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(09)70149-5

Matrix metalloproteinase (MMP)-2 and -9 (gelatinases) participate in extracellular protein remodeling. Moreover, they are involved in the development of hepatic fibrosis. The goal of this study was to evaluate liver gelatinase activities after erythropoietin (Epo) treatment (1U/dose, sc) in experimentally damaged livers of rats treated with D-galactosamine (Gal, 800mg/kg/dose, ip).Sixty rats were divided into six equal groups: I – received 5 doses of Epo anda single dose of Gal [the experiment duration (ED): 10 days]; II – received 5 doses of Epo and 3 doses of Gal (ED: 14 days); III – received only 5 doses of Epo (ED: 9 days); IV – received 3 doses of Gal (ED: 5 days); V–received a single dose of Gal (ED: 1 day); VI – control group (ED: 9 days). The animals were sacrificed and the livers were collected 48h after the last drug administration. The activity of gelatinases was measured using gelatin zymography. No fluctuations in gelatinase activities were observed after the administration of a single dose of Gal in comparison to the control group. However, a significant increase in gelatinase activities was observed after treatment with three doses of Gal. Five doses of Epo administrated before Gal treatment prevented elevated gelatinase activities: MMP-9 activity was comparable to control, and MMP-2 activity was decreased (group II). The gelatinase activities was lower in group I and II in comparison to the control group. These results revealed that Epo decreases MMP-2 and MMP-9 activity, suggesting that it is a hepatoprotective agent against hepatic damage induced by galactosamine injection.