Exposure to the environmental pollutant chlorpyrifos induces hepatic toxicity through activation of the JAK/STAT and MAPK pathways
Chlorpyrifos (CHP) is an inexpensive highly effective organophosphate insecticide used worldwide. The unguided and excessive use of CHP by farmers has led to its significant accumulation in crops as well as contamination of water sources, causing health problems for humans and animals. Therefore, th...
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Veröffentlicht in: | The Science of the total environment 2024-06, Vol.928, p.171711-171711, Article 171711 |
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Zusammenfassung: | Chlorpyrifos (CHP) is an inexpensive highly effective organophosphate insecticide used worldwide. The unguided and excessive use of CHP by farmers has led to its significant accumulation in crops as well as contamination of water sources, causing health problems for humans and animals. Therefore, this study evaluated the toxicological effects of exposure to the environmental pollutant CHP at low, medium, and high (2.5, 5, and 10 mg·kg−1 BW) levels on rat liver by examining antioxidant levels, inflammation, and apoptosis based on the no observed adverse effect levels (NOAEL) (1 mg·kg−1 BW) and the CHP dose that does not cause any visual symptoms (5 mg·kg−1 BW). Furthermore, the involvement of the JAK/STAT and MAPK pathways in CHP-induced toxic effects was identified. The relationship between the expression levels of key proteins (p-JAK/JAK, p-STAT/STAT, p-JNK/JNK, p-P38/P38, and p-ERK/ERK) in the pathways and changes in the expression of markers associated with inflammation [inflammatory factors (IL-1β, IL-6, IL-10, TNF-α), chemokines (GCLC and GCLM), and inflammatory signaling pathways (NF-кB, TLR2, TLR4, NLRP3, ASC, MyD88, IFN-γ, and iNOS)] and apoptosis [Bad, Bax, Bcl-2, Caspase3, Caspase9, and the cleavage substrate of Caspase PARP1] were also determined. The results suggest that CHP exposure disrupts liver function and activates the JAK/STAT and MAPK pathways via oxidative stress, exacerbating inflammation and apoptosis. Meanwhile, the JAK/STAT and MAPK pathways are involved in CHP-induced hepatotoxicity. These findings provide a novel direction for effective prevention and amelioration of health problems caused by CHP abuse in agriculture and households.
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•CHP disrupts liver function, causing oxidative stress, inflammation, and apoptosis.•JAK/STAT and MAPK pathways worsen hepatotoxicity via oxidative stress.•Key protein expressions relate to inflammation/apoptosis markers.•Unregulated CHP use poses health risks in agriculture and households.•Study offers strategies against CHP-induced health issues. |
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ISSN: | 0048-9697 1879-1026 |
DOI: | 10.1016/j.scitotenv.2024.171711 |