Effect of anakinra, tocilizumab, and the combination thereof on bladder ischemia-reperfusion damage in albino Wistar-type rats.

Abstract

Several studies have reported that oxidative stress, and proinflam-matory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL -1β), and interleukin-six (IL -6) are the main factors underlying bladder ischemia-reperfusion (I/R) damage. Anakinra and tocilizumab are known to be antioxidants and proinflammatory cytokine inhibitors. Our study aims to investigate if anakinra, tocilizumab, and the combination (ATC) thereof have a protective effect against oxidative and inflammatory bladder damage induced through the I/R procedure in rats, and evaluate by comparing these compounds. Male rats were divided into five groups: bladder sham-operation applied group (SG); bladder only I/R applied group (IRG); anakinra+bladder I/R applied group (AIR); tocilizumab+bladder I/R applied group (TIR); and ATC+bladder I/R applied group (ATIR). An atraumatic clamp was placed on the abdominal aorta of animals in all groups (except SG), and one hour of ischemia followed by two hours of reperfusion was performed. Our biochemical find-ings showed that anakinra and tocilizumab significantly inhibited the increase of oxidant malondialdehyde (MDA) and the decrease of antioxidants such as total glu-tathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in bladder tissue by I/R, both at the same levels. Furthermore, anakinra and tocilizumab significantly suppressed the I/R-associated increase of TNF-α, IL -1β, and IL -6 in bladder tissue. ATC was the one that best prevented the I/R-related increase in MDA, TNF-α, IL -1β, and IL -6 and the decrease in tGSH, SOD, and CAT in the bladder tissue. ATC was more beneficial than anakinra or tocilizumab alone in treating bladder I/R damage.