Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

• Published in: Canadian journal of physiology and pharmacology 2017-07, Vol.95 (7), p.866-872
• Main Authors: Ozer, Erdem Kamil, Goktas, Mustafa Tugrul, Kilinc, Ibrahim, Toker, Aysun, Bariskaner, Hulagu, Ugurluoglu, Ceyhan, Iskit, Alper Bektas
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Aorta - drug effects; Aorta - physiopathology; Blood Circulation - drug effects; Care and treatment; dysfonctionnement d’organes multiples; Female; flux sanguin artériel mésentérique; Immunotherapy; Infliximab; Infliximab - pharmacology; Interleukin-6 - metabolism; mesenteric arterial blood flow; Mesentery - blood supply; Monoclonal antibodies; multiple organ dysfunction; Multiple Organ Failure - complications; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiopathology; Oxidative stress; Patient outcomes; Pharmacology; Physiological aspects; Physiology; Rats; Rats, Wistar; Rodents; réactivité vasculaire; Sepsis; Sepsis - complications; Sepsis - mortality; Sepsis - pathology; Sepsis - physiopathology; septicémie; survie; survival; Tissues; TNF inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; vascular reactivity
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2016-0628

Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.