Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with naturally occurred endotoxic shock S. S ¸ ENTU ¨ RK Department of Internal Medicine, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey S ¸ entu ¨ rk, S. Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with naturally occurred endotoxic shock. J. vet. Pharmacol. Therap. 28, 57–63. Endotoxin is a potent stimulator of the inflammatory response and is believed to initiate the pathology in gram-negative sepsis. Agents are being searched for that bind and neutralize or block the effects of endotoxin. The aim was to study the anti-endotoxic effects of polymyxin-E (colistin) in endotoxaemic dogs. The study included a total of 30 endotoxaemic dogs, which were divided into two groups (control ¼ 15; test ¼ 15) of both sexes, different breeds and ages. Hetastarch colloid solution (Expahes Ò ,10 mL/kg, i.v.) with lactated Ringer’s solution (20 mL/kg, i.v., Q12 h) was given to all dogs. While ampicillin was administered (Alfasilin Ò , 10 mg/kg, i.m., Q12 h) as an antibacterial to the control group, colistin (12 500 IU/kg, i.m., Q12 h) + ampicillin were admin- istered to the test group. The clinical examination (body temperature, pulse and respiration rates, capillary filling times, peripheral pulse qualities, dehydration degrees), hematological and biochemical examinations (WBC, RBC, HGB, HCT, thrombocyte, serum urea, creatinine and TNF-a) were performed both before the treatment, and 2, 4, 12 and 24 h after the treatment. In comparison with the control group, it was observed that test group had shorter capillary filling time at 24 h (P < 0.001). Moreover, the degree of dehydration in test group, was significantly improved at 24 h (P < 0.01). While the differences in peripheral pulse qualities significantly differed between 0 and 2 h in controls, at 2, 4, 24 h after treatment it was found to be significantly increased when compared with 0 h in the test group. Serum TNF-a concentrations were statistically decreased in the test group between 0h and other times (P < 0.01). When compared with controls, serum TNF-a concentrations were lower at 2, 4, 12 and 24 h in test group (P < 0.05). Results of the study indicated that polymyxin-E (colistin) has an anti-endotoxic effect and is safe for the dogs with endotoxemia at the dosage used in this study. (Paper received 30 July 2004; accepted for publication 26 October 2004) Sezgin S ¸ entu ¨rk, Veteriner Faku ¨ltesi Klinikleri, Uludag U ¨ niversitesi, _ Ic ¸ Hastalıkları Ana Bilim Dalı, Mudanya caddesi no. 2, 16190 Bursa, Turkey. E-mail: sezsen8@yahoo.com INTRODUCTION Despite the advances in supportive care, endotoxic shock remains to be one of the leading causes of death in critically ill patients. The endotoxin or lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria is its major pathogenic factor, and a potent activator of the immune and inflammatory systems, including macrophages, monocytes, and endothelial cells. It contributes to the systemic changes seen in endotoxic shock (Barton et al., 2000). The systemic changes are characterized by systemic inflammation, multiple organ damage, circulatory collapse, the disruption of normal homeostasis, and death (Deldar et al., 1984; Constable et al., 1991a,b; Barton et al., 2000). One central endotoxin-induced interaction between LPS and macrophages results in release of cytokines. Tumor necrosis factor-alpha (TNF-a) is the most important cytokine released during endotoxemia (Bone, 1990; Kenison et al., 1991; Spooner et al., 1992; Miyamoto et al., 1996; Barton et al., 2000; Zhang et al., 2001). TNF-a is a protein secreted by lipopolysac- charide-stimulated macrophages. TNF-a is believed to mediate pathogenic shock and tissue injury associated with endotoxemia (Morrison & Ryan, 1987; Kenison et al., 1991; Barton et al., J. vet. Pharmacol. Therap. 28, 57–63, 2005. ANTIINFECTANTS Ó 2005 Blackwell Publishing Ltd 57