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Keywords
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Antioxidant, Anti-inflammatory, Endotoxemia, Lipopolysaccharide, Troxerutin
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Abstract
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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 antiinflammatory
agent for the treatment of LPS-induced sepsis.
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