Effect of Pentoxifylline on Antioxidant Status of Healthy and Endotoxemic New Zealand White Rabbits

Abstract

Keskin E. , E. Oztekin (Menevse) , R. Col , A. Sivr ikaya, K. Uney, E. Yazar: Effect of Pentoxifylline on Antioxidant Status of Healthy and Endotoxemic New Zealand White Rabbits. Acta Vet. Brno 2005, 74: 17-21. In this study, effect of pentoxifylline on antioxidant status of healthy and endotoxemic rabbits was investigated. Endotoxemia was induced with E. coli lipopolysaccharide in New Zealand white rabbits. Forty rabbits were randomly divided into four equal groups. Group 1 served as control. Animals in Group 2 were given lipopolysaccharide (400 μg/kg) intravenously, in Group 3 pentoxifylline (50 mg/kg) was injected intraperitoneally. In Group 4; pentoxifylline (50 mg/kg intraperitoneally) and lipopolysaccharide (400 μg/kg, intravenously) were injected simultaneously. Animals were killed, and liver, heart and kidney samples were taken at 6 hours after administrations. Malondialdehyde, superoxide dismutase, glutathione peroxidase and reduced glutathione levels of heart, liver and kidney tissues were measured. Lipopolysaccharide caused significant increases (p < 0.05) in hepatic malondialdehyde, and cardiac, hepatic and renal glutathione peroxidase activities. It however, caused significant (p < 0.05) decrease in hepatic superoxide dismutase activity when compared to control group. Pentoxifylline caused significant (p < 0.05) increases of cardiac and hepatic malondialdehyde levels, cardiac superoxide dismutase and renal glutathione peroxidase activities, and cardiac, hepatic and renal reduced glutathione levels when compared to control group. As a result, pentoxifylline has no exactly beneficial effect on the antioxidant status of healthy and endotoxaemic New Zealand white rabbits at the administered dose and route. Although it was stated that pentoxifylline may be beneficial in endotoxaemia, its antioxidant effect may be dependent on dose, administration route and animal species. For this reason, when pentoxifylline is used in endotoxaemia, a treatment protocol should be done for each animal species. Pentoxifylline, lipopolysaccharide, antioxidant status, rabbits Lipopolysaccharide (LPS), a major component of the outer membranes of gram (-) bacteria, is released during infection and induces a number of pathological reactions leading to cardiovascular failure and damage to numerous organs. LPS can elicit a systemic inflammatory response syndrome defined as sepsis. When sepsis is accompanied by hypotension plus organ dysfunction, the condition is known as septic shock and the mortality of animals in septic shock has remained high. The common mechanism of tissues damage in the septic shock may be related to widespread vascular endothelial injury and microthrombosis. Homeostasis fails and dysfunction of major organs (heart, kidney, liver) may occur (Hardaway 2000; Cadenas and Cadenas 2002). There is convincing evidence of severe oxidative stress in sepsis. Oxidative stress occurs when antioxidant balance is disrupted by excessive production of reactive oxygen species (ROS) such as superoxide radical, hydroxyl radical, hydrogen peroxide, singlet oxygen and/or by inadequate antioxidant defense mechanisms such as superoxide dismutase (SOD) ACTA VET. BRNO 2005, 74: 17–21 Address for correspondence: Dr. Enver Yazar Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Selcuk 42031, kampus Konya, Turkey Phone: +903 322 410 041 Fax: +903 322 410 063 e-mail: eyazar@selcuk.edu.tr http://www.vfu.cz/acta-vet/actavet.htm