Modulation of zymosan-induced peritonitis by riboflavin co-injection, pre-injection or post-injection in male Swiss mice

Aims: We compared the effects of riboflavin pre-injection, co-injection and post-injection on several symptoms of zymosan-induced peritonitis in male Swiss mice. Additionally, the effects of i.p. injection of riboflavin itself were elucidated. Main methods: Peritonitis was induced in Swiss mice (50 animals) by i.p. zymosan (Z; 40 mg/kg) injection. Riboflavin (R; 0, 20, 50, or 100 mg/kg) was applied either alone or in combination with zymosan. In the latter case riboflavin was administered either together with zymosan (R group), or 30 min before zymosan (R-Z group), or 1 h later (Z-R group). The nociceptive response was evaluated by counting body writhes. The peritoneal exudates retrieved 4 h after the R or Z injection were analyzed for the numbers and apoptosis of polymorphonuclear leukocytes (PMNs). and levels of metalloproteinase 9 (MMP-9), nitric oxide, and inflammatory cytokines, IL-12p70, TNF alpha, MCP-1, IL-6, IL-10, IFN gamma. Key findings: Riboflavin itself induced nociceptive-related body writhes and a moderate inflammatory response manifested by PMN influx and the release of some cytokines and MMP-9. In contrast, antinociceptive properties of riboflavin were significant in the ZR group co-injected with the lowest dose of riboflavin (ZR20). At the 4th hour of zymosan-induced peritonitis an intraperitoneal accumulation of PMNs was decreased in the riboflavin-treated groups and cytokine profiles were modified according to riboflavin dose and the time of injection. Significance: Riboflavin itself induces low-grade nociception and inflammation while its effects on zymosan-induced inflammation are dependent on the dose and time of its application: either before or during inflammation. (C) 2012 Elsevier Inc. All rights reserved.