PMID- 22938100
OWN - NLM
STAT- MEDLINE
DCOM- 20130307
LR  - 20131121
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 25
IP  - 10
DP  - 2012 Oct 15
TI  - Immunotoxicity induced by acute subtoxic doses of paraquat herbicide: implication 
      of shifting cytokine gene expression toward T-helper (T(H))-17 phenotype.
PG  - 2112-6
LID - 10.1021/tx300194t [doi]
AB  - Paraquat (PQ) is a free radical-inducing agent commonly used as an herbicide. 
      This study assesses the acute immunotoxicity of PQ in BALB/c mice and examines 
      its effect on cytokine gene expression profile. It was found that single subtoxic 
      oral doses of 2, 4, and 20 mg/kg significantly inhibited the in vitro 
      mitogen-induced proliferation in both T and B cells. Also, such acute doses have 
      resulted in significant reduction of the IgM plaque-forming cells counts. The 
      impact of PQ on the cytokine gene expression of in vitro PHA-activated 
      splenocytes was assessed at 2.0 and 0.006 mug/mL. The concentrations used in vitro 
      represent the lowest in vivo dose given in this study and FAO-WHO set PQ 
      acceptable daily intake (ADI) dose, respectively. Interestingly, the RT(2)-PCR 
      array for common cytokines' expression demonstrated that PQ had markedly elevated 
      the mRNA expression of several proinflammatory cytokines at both concentrations. 
      More importantly, at concentrations equivalent to ADI, PQ had caused a marked 
      up-regulation of IL-17 cytokine family including IL-17B, C, E, and F. Also, PQ 
      has up-regulated mRNA expression of the T(H)-17-promoting cytokines IL-9 and -21. 
      Together, these results show that PQ at higher concentrations can deplete immune 
      functions, but at lower concentrations, it has potential to alter immune 
      responses toward the proinflammatory profiles as that of T(H)-17. Such a T cell 
      helper profile has been implicated in the development and the pathophysiology of 
      several autoimmune and allergic diseases. Thus, considering that maximum residue 
      levels (MRLs) of PQ set by FAO and WHO for certain food and animal feed crops 
      range between 0.005 and 10.0 mg/kg, our findings stress the importance of 
      applying strict regulation on the use of PQ as an herbicide.
FAU - Hassuneh, Mona R
AU  - Hassuneh MR
AD  - Department of Biological Sciences, Faculty of Science, University of Jordan, 
      Amman 11942, Jordan. hassuneh@yahoo.com
FAU - Albini, Maysaa' A
AU  - Albini MA
FAU - Talib, Wamidh H
AU  - Talib WH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120921
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Cytokines)
RN  - 0 (Herbicides)
RN  - 0 (RNA, Messenger)
RN  - PLG39H7695 (Paraquat)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antibody Formation/drug effects
MH  - B-Lymphocytes/drug effects/immunology
MH  - Cytokines/*genetics
MH  - Female
MH  - Hematologic Tests
MH  - Herbicides/administration & dosage/*immunology/toxicity
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Paraquat/administration & dosage/*immunology/toxicity
MH  - RNA, Messenger/genetics
MH  - Spleen/cytology/drug effects/metabolism
MH  - T-Lymphocytes/drug effects/immunology
MH  - Th17 Cells/drug effects/*immunology/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2012/09/04 06:00
MHDA- 2013/03/08 06:00
CRDT- 2012/09/04 06:00
PHST- 2012/09/04 06:00 [entrez]
PHST- 2012/09/04 06:00 [pubmed]
PHST- 2013/03/08 06:00 [medline]
AID - 10.1021/tx300194t [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2012 Oct 15;25(10):2112-6. doi: 10.1021/tx300194t. Epub 2012 
      Sep 21.