PMID- 34778934
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220405
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 96
IP  - 1
DP  - 2022 Jan
TI  - Organophosphorus pesticides exhibit compound specific effects in rat 
      precision-cut lung slices (PCLS): mechanisms involved in airway response, 
      cytotoxicity, inflammatory activation and antioxidative defense.
PG  - 321-334
LID - 10.1007/s00204-021-03186-x [doi]
AB  - Organophosphorus compound pesticides (OP) are widely used in pest control and 
      might be misused for terrorist attacks. Although acetylcholinesterase (AChE) 
      inhibition is the predominant toxic mechanism, OP may induce pneumonia and 
      formation of lung edema after poisoning and during clinical treatment as 
      life-threatening complication. To investigate the underlying mechanisms, rat 
      precision-cut lung slices (PCLS) were exposed to the OP parathion, malathion and 
      their biotransformation products paraoxon and malaoxon (100-2000 micromol/L). Airway 
      response, metabolic activity, release of LDH, cytokine expression and oxidative 
      stress response were analyzed. A concentration-dependent inhibition of airway 
      relaxation was observed after exposure with the oxon but not with the thion-OP. 
      In contrast, cytotoxic effects were observed for both forms in higher 
      concentrations. Increased cytokine expression was observed after exposure to 
      parathion and paraoxon (IL-6, GM-CSF, MIP-1alpha) and IL-6 expression was dependent 
      on NFkappaB activation. Intracellular GSH levels were significantly reduced by all 
      four tested OP but an increase in GSSG and HO-1 expression was predominantly 
      observed after malaoxon exposure. Pretreatment with the antioxidant 
      N-acetylcysteine reduced malaoxon but not paraoxon-induced cytotoxicity. PCLS as 
      a 3D lung model system revealed OP-induced effects depending on the particular 
      OP. The experimental data of this study contribute to a better understanding of 
      OP toxicity on cellular targets and may be a possible explanation for the variety 
      of clinical outcomes induced by different OP.
CI  - (c) 2021. The Author(s).
FAU - Tigges, Jonas
AU  - Tigges J
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Worek, Franz
AU  - Worek F
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Wille, Timo
AU  - Wille T
AUID- ORCID: 0000-0002-4359-5388
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany. TimoWille@bundeswehr.org.
AD  - Department CBRN Medical Defence, Bundeswehr Medical Academy, Ingolstadter Str. 
      240, 80939, Munich, Germany. TimoWille@bundeswehr.org.
LA  - eng
GR  - GRK 2338/DFG/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211115
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Antioxidants)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Pesticides)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Lung
MH  - Organophosphorus Compounds/toxicity
MH  - *Pesticides/toxicity
MH  - Rats
PMC - PMC8748323
OTO - NOTNLM
OT  - Bronchoconstriction
OT  - Inflammation
OT  - Organophosphates
OT  - Oxidative stress
OT  - PCLS
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/11/16 06:00
MHDA- 2022/04/05 06:00
PMCR- 2021/11/15
CRDT- 2021/11/15 07:19
PHST- 2021/08/10 00:00 [received]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/11/16 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/11/15 07:19 [entrez]
PHST- 2021/11/15 00:00 [pmc-release]
AID - 10.1007/s00204-021-03186-x [pii]
AID - 3186 [pii]
AID - 10.1007/s00204-021-03186-x [doi]
PST - ppublish
SO  - Arch Toxicol. 2022 Jan;96(1):321-334. doi: 10.1007/s00204-021-03186-x. Epub 2021 
      Nov 15.