Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 10 No. 5 October 06, 2023 p.221-231
Original Article
Effect of Anakinra (Kineret®) treatment on acrylamide-induced neurotoxicity in mice
  • Gaku Ichihara (Department of Occupational and Environmental Health, Tokyo University of Science / gak@rs.tus.ac.jp)
Alzahraa Fergany 1) 2) , Frederick Adams Ekuban 1) , Cai Zong 1) , Gaku Ichihara 1)
1) Department of Occupational and Environmental Health, Tokyo University of Science , 2) Laboratory of Genetics and Genetic Engineering in Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University
Keywords: Anakinra, Acrylamide, Neurotoxicity, Noradrenergic axons, Microglia, Neuroinflammation
Abstracts

Recent studies demonstrated that upregulation of proinflammatory cytokines were associated with neurotoxicity of acrylamide, which is used widely in industries and generated in food cooked at high temperature. The interleukin-1 (IL-1) is one of cytokines that play an important role in immune response. Anakinra is an IL-1 receptor antagonist used as anti-inflammatory medicine against inflammatory diseases such as juvenile idiopathic arthritis. In this study, ten-week old wild type male mice were allocated into 6 groups. Group 1 to 3 daily received subcutaneous injection with vehicle and oral exposure to ACR in drinking water at 0, 150 or 300 ppm for 28 days, and group 4-6 daily received injection with Anakinra and oral exposure to ACR in drinking water at 0, 150 or 300 ppm for 28 days. The landing foot spread (LFS) test was carried out to assess the motor function, and immunohistochemistry was carried out for quantification of noradrenergic axons and microglia activation. The results of LFS did not show significant effect of Anakinra treatment on ACR-induced increase in landing foot spread in mice. The body weight was dose-dependently decreased by ACR exposure only in the groups treated with Anakinra. The IHC staining for microglia and noradrenergic axon density does not show any significant effect of treatment with Anakinra or exposure to ACR. The study demonstrated that daily treatment with Anakinra at 25 mg/kg body weight does not ameliorate ACR-induced neurotoxicity in mice, while potentiates ACR-induced loss of body weight.