Troxerutin attenuates inflammatory response in lipopolysaccharide-induced sepsis in mice

• Published in: Research in veterinary science 2021-03, Vol.135, p.469-478
• Main Authors: Jafari-Khataylou, Yaser, Emami, Seyyed Jamal, Mirzakhani, Navideh
• Format: Article
• Language: English
• Subjects: Acids; Alanine; Alanine transaminase; Anti-inflammatory; Anti-inflammatory agents; Anticancer properties; Antioxidant; Antioxidants; Bacteria; Catalase; CD40 antigen; Cytokines; Dosage; Endotoxemia; Flavonoids; Infections; Inflammation; Inflammatory response; L-Lactate dehydrogenase; Laboratory animals; Lactate dehydrogenase; Lactic acid; Lethal dose; Leukocytes; Lipopolysaccharide; Lipopolysaccharides; Malondialdehyde; Medical research; Mortality; Nitric oxide; Peroxidase; Rutin; Sepsis; Splenocytes; Superoxide dismutase; Survival; Troxerutin; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2020.11.020

Troxerutin (Tx), known as vitamin P4 is a derivative of natural bioflavonoid rutin. Tx possesses different biological activities such as antioxidant, anticancer, and anti-inflammatory. The current study was conducted to determine potential therapeutic effect of Tx in lipopolysaccharides (LPS)-induced sepsis in mice. In LPS-induced sepsis, the mice were treated intraperitoneally (ip) with Tx twice daily. Therapeutic effect was assessed by measuring serum level of cytokines, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Level of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), Myeloperoxidase (MPO) and Malondialdehyde (MDA) was measured. Expression of CD40 receptor on leucocytes was measured using flowcytometry. Splenocyte proliferation was evaluated using MTT assay. The effect of Tx on survival rate during administration of lethal dose of LPS was investigated. The results showed that Tx inhibited LPS induced NO production. Inflammatory pathways were suppressed by reduction of inflammatory cytokines production. Further, elevated CD40 expression of leucocytes and proliferation of splenocytes markedly reduced in Tx treated group. Antioxidant defense system was enhanced by increased activity of SOD and CAT and decreased level of MDA. MPO, ALT and LDH activity. Additionally, treatment with Tx significantly increased the mean survival time of mice compared with the LPS treated group. Histologically, Tx treatment decreased inflammatory cells infiltration and histopathologicl changes in the liver. Our findings showed that reduced inflammatory parameters, improved antioxidant activity, reduced histological lesions and increased survival rate. These findings suggest that Tx is an effective anti-inflammatory agent for the treatment of LPS-induced sepsis. •Troxerutin decreases pro and inflammatory cytokines in serum of septic mice.•Troxerutin suppresses oxidative stress and enhanced antioxidant activity in septic mice.•Troxerutin restored splenocyte proliferation, MPO activity and CD40 expression to normal level.•Troxerutin improved survival rate in septic mice.•Troxerutin alleviated the LPS induced histopathological lesions in liver.