Evaluation of the anti‐endotoxic effects of polymyxin‐E (colistin) in dogs with naturally occurred endotoxic shock

Abstract

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 = 15; test = 15) of both sexes, different breeds and ages. Hetastarch colloid solution (Expahes,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, 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 administered 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-alpha) 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-alpha concentrations were statistically decreased in the test group between 0 h and other times (P < 0.01). When compared with controls, serum TNF-alpha 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.

Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives

“…Colistin also exerts an anti-endotoxin activity because it binds to the lipid A component of LPS (Falagas et al, 2005; Şentürk, 2005). In this way, colistin prevents endotoxin’s ability to induce shock through the release of cytokines such as tumor necrosis factor-alpha (TNF-α) and IL-8 (Şentürk, 2005; Baeuerlein et al, 2009).…”

“…In this way, colistin prevents endotoxin’s ability to induce shock through the release of cytokines such as tumor necrosis factor-alpha (TNF-α) and IL-8 (Şentürk, 2005; Baeuerlein et al, 2009). …”

“…Furthermore, it was shown that colistin used at the dose of 12. 500 IU/kg IM for 5 days in combination with ampicillin had demonstrated an anti-endotoxic effects in dogs with naturally occurring endotoxic shock (Şentürk, 2005). Despite the isolation of E. coli resistant to polymyxins harboring the mcr-1 gene from dogs and cats, it is difficult to determine the role of polymyxin B administered topically in the exacerbation of colistin resistance in dog’s or cat’s intestine.…”

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna

“…Serum TNF-α was measured by ELISA using an enzyme-linked immunoassay kit (Rat TNF-α ELISA kit, Biosource International, Inc., Camarillo, CA, USA) according to the manufacturer's protocol [29,30]. TNF-α content was expressed as pg/ml.…”

Characterization of an Indigenous Antimicrobial Substance-producing Paenibacillus sp. BCNU 5011

“…그 외 circulin, lantibiotic 등 [12,13] 도 생산되고 있음이 보고되고 있으며, P. kobensis M으로 부터 분리된 polymyxin M (mattacin), P. thiamunolyticus 로부터 octopygtin과 baciphelacin 등이 분리 보고되고 있 다 [14,15]. P. polymyxa 균주가 생산하는 polymyxin은 그람 음성 세균에 대한 강력한 항균효과를 나타냄으로써 1970년 대 초반까지 병원성 미생물에 의한 질병 치료제로서 많이 사용되어 왔으나, 신경독성과 간독성 등의 부작용을 동반하 여 그 사용이 줄어들었다 [16,17]. 그러나 polymyxin이 β-lactam계, aminoglycoside계 및 fluoroquinolone계 항생제에 내성을 보이는 Pseudomonas aeruginosa 및 Acinetobacter baumannii 등의 다제내성 세균에 대해 탁월한 살균효과를 가진 것이 입증되면서 다시 주목을 받고 있다 [18,19].…”