Protective effect of anisodamine against Shiga toxin-1: inhibition of cytokine production and increase in the survival of mice.
The purpose of this study was to investigate whether anisodamine could inhibit Shiga toxin-1 (Stx1)-induced cytokine production and increase the survival of Stx1-treated mice. Human monocytic cells were stimulated by Stx1 (1 to 100 ng/mL) with or without anisodamine addition (1 to 400 microg/mL). For in vivo evaluations, C57BL/6 mice were given a single intraperitoneal injection of anisodamine (1 mg) or saline solution after intraperitoneal injection of Stx1 (2.75 microg/kg). The results showed that anisodamine significantly suppressed Stx1-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-8 production. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that anisodamine suppressed Stx1-mediated TNF-alpha mRNA expression. Further study showed that this TNF-alpha inhibitory effect was via a prostaglandin E2-dependent mechanism. Anisodamine treatment prolonged the survival time of mice and decreased the lethality of Stx1 (94.5% to 44%). Because cytokines, in particular TNF-alpha, contribute to the pathologic process in Stx-producing Escherichia coli (STEC) infection, this study suggested that anisodamine could be a potential drug for treatment of STEC infection.
Zhang
H M
HM
Department of Bacteriology, Niigata University School of Medicine, Niigata, Japan.
Ou
Z L
ZL
Gondaira
F
F
Ohmura
M
M
Kojio
S
S
Yamamoto
T
T
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000502:physiology; D004927:Escherichia coli Infections / Q000188:drug therapy; D015870:Gene Expression; D006801:Humans; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022622:Shiga Toxin 1 / Q000633:toxicity*; D012991:Solanaceous Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D022622:Shiga Toxin 1; D012991:Solanaceous Alkaloids; D014409:Tumor Necrosis Factor-alpha; C003922:anisodamine; D015232:Dinoprostone