The Antimalarial Artemisinin Synergizes with Antibiotics to Protect against Lethal Live E.Coli Chalenge by Decreasing Proinflammatory Cytokine Release  

Oleh:

[s.n]

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Antimicrobial Agents and Chemotherapy vol. 50 no. 07 (Jul. 2006), page 2420.
Topik: Antimalarial Artemisinin Synergizes; Proinflammatory Cytokine

Ketersediaan

Perpustakaan FK Nomor Panggil: A21.K, A21.K.2006.03 Non-tandon: 3 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

In the present study artemisinin (ART) was found to have potent anti-inflammatory effects in animal models of sepsis induced by CpG-containing oligodeoxy-nucleotides (CpG ODN), lipopolysaccharide (LPS), heat-killed E.Coli 35218 or live E.coli. Furthermore, we found that ART protected mice from a lethal chaleenge by CpG ODN, LPS, or heat-killed E.coli in a dose-sependent manner and that the protection was related to a reduction in serum tumor necrosis factor alpha (TNF-alpha). More significantly, the administration of ART together with ampicillin or unasyn ( a complex of ampicillin and sulbactam) decreased mortality from 100 to 66.7% or 33.3%, respectively, in mice subjected to a lethal live E.Coli challenge. Together with the observation that ART alone does not inhibit TNF-alpha and interleukin-6 release induced by CpG ODN, LPS, or heat-killed E.coli in a dose and time-dependent manner. Experiments utilizing affinity sensor technology revealed no direct binding of ART with CpG ODN or LPS. Flow cytometry further showed that ART did not alter binding of CpG ODN to cell sufaces or the internalization of CpG ODN. In addition, upregulated levels of TLR9 and TLR4 mRNA were not attenuated by ART treatment. ART treatment did, however, block the NF-kB activation induced by CpG ODN, LPS, or heat-killed E.coli. THese findings provide compelling evidence that ART may be an important potential drug for sepsis treatment.

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