8 O. COSKUN ET AL. Copyright © 2005 John Wiley & Sons, Ltd. J. Appl. Toxicol. 2005; 25: 8–12 JOURNAL OF APPLIED TOXICOLOGY J. Appl. Toxicol. 2005; 25: 8–12 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jat.1002 Protection of endotoxin-induced oxidative renal tissue damage of rats by vitamin E or/and EGb 761 treatment Omer Coskun, 1, * Ferah Armutcu, 2 Mehmet Kanter 1 and Gamze Mocan Kuzey 3 1 Zonguldak Karaelmas University, Faculty of Medicine, Department of Histology and Embryology, Zonguldak, Turkey 2 Zonguldak Karaelmas University, Faculty of Medicine, Department of Biochemistry, Zonguldak, Turkey 3 Hacettepe University, Faculty of Medicine, Department of Pathology, Ankara, Turkey Received 6 August 2003; Revised 29 January 2004; Accepted 17 February 2004 ABSTRACT: The aim of the present study was to evaluate the possible protective effects of vitamin E and EGb 761 treatments, alone or in combination, against oxidative renal tissue damage in experimentally induced endotoxaemic rats. Fifty healthy male Wistar albino rats, weighing 150–250 g and averaging 12 weeks old, were allotted randomly into one of five experimental groups: A (untreated), B (endotoxaemic), C (endotoxaemic + vitamin E treated), D (endotoaxemic + EGb 761 treated) and E (endotoxaemic + vitamin E and EGb 761 treated), each containing ten animals. Group A received only an intraperitoneal (i.p.) injection of 2 ml of normal saline solution and served as the control. Groups B, C, D and E were administrated a single i.p. injection of 0.5 ml of endotoxin solution. In addition, groups C, D and E received i.p. injections of 600 mg kg -1 body mt. of vitamin E and oral extract of 50 mg kg -1 body wt. of EGb 761, alone or in com- bination, immediately after the endotoxin injection. The experiment lasted for 24 h. At the end of the experiment blood and tissue samples were obtained for biochemical and histopathological investigation. Endotoxin injection produced renal damage, increased lipid peroxidation and decreased antioxidant enzyme activity. Vitamin E or/and EGb 761 treat- ment decreased lipid peroxidation, increased antioxidant enzyme activity and also prevented renal tissue damage in experimentally induced endotoxaemic rats. In conclusion, vitamin E and EGb 761 treatment, alone or in combination, ap- pears to be beneficial in preventing endotoxin-induced oxidative renal tissue damage and therefore shows potential for clinical use. Copyright © 2005 John Wiley & Sons, Ltd. KEY WORDS: endotoxaemia; vitamin E; EGb 761; lipid peroxidation; kidney * Correspondence to: Dr Omer Coskun, Zonguldak Karaelmas Üniversitesi, Tıp Fakültesi, Histoloji-Embriyoloji AD, Zonguldak, Turkey. E-mail: omercoskun1970@hotmail.com Introduction Endotoxin released from Gram-negative bacteria acts as a potent signalling molecule that can elicit a sys- temic inflammatory response syndrome (SIRS) defined as sepsis. The onset of sepsis is characterized by fever or hypothermia, tachycardia and tachypnoea (Cadenas and Cadenas, 2002). When sepsis is accompanied by hypoten- sion plus organ dysfunction, the condition is known as septic shock. Despite significant progress in understand- ing the pathophysiology of sepsis and septic shock, these conditions continue to be the prime causes of morbidity and mortality in intensive-care units (Westphal et al., 2002). Endotoxin has harmful effects on various organs, including the kidney, through the induction of inflamma- tory mediators (Cadenas and Cadenas, 2002). The occur- rence of the functional organ insufficiencies in sepsis depends on the duration of this septic status (Ozdulger et al., 2002). The common mechanism by which tissues are damaged by the septic response is probably related to widespread vascular endothelial injury and micro- thrombosis. These, in turn, decrease the oxygen and substrate supply to the tissues, leading to anaerobic metabolism and the production of free oxygen radicals (Cadenas and Cadenas, 2002). Lipid peroxidation is associated with a wide variety of toxicological effects, including decreased membrane fluidity and function, impaired mitochondrial and Golgi apparatus functions and inhibition of enzymes. Malondialdehyde (MDA) is an end product of lipid peroxidation and is a fre- quently measured index of these processes (Slater, 1984; Comporti, 1989). Malondialdehyde can cross-link with membrane constituents of erythrocyte. Vitamin E (α- tocopherol) is believed to be involved in a variety of physiological and biochemical functions. The molecular mechanism of these functions is believed to be mediated by either the antioxidant action of the vitamin or by its action as a membrane stabilizer (Wang and Quinn, 1999). Antioxidant systems such as antioxidant vitamins (vitamins A, C and E), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), ceruloplasmin and glutathione peroxidase (GSH-Px) protect the cells against lipid peroxidation, which is the basis of many patholog- ical processes (Williams, 1984; Bray and Bettger, 1990). EGb 761 is a standardized extract of Ginkgo biloba leaves and has antioxidant properties as a free-radical scavenger (Li et al., 2003). A standardized extract of