Circadian rhythm in mycotoxin-induced immunotoxicity: an emerging regulatory axis?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10505408" target="_blank" >RIV/00179906:_____/25:10505408 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18450/25:50022799 RIV/62690094:18470/25:50022799 RIV/61989100:27360/25:10259719

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OTCj.QCRWH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OTCj.QCRWH</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2025.1700863" target="_blank" >10.3389/fphar.2025.1700863</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Circadian rhythm in mycotoxin-induced immunotoxicity: an emerging regulatory axis?

Popis výsledku v původním jazyce

Mycotoxins, toxic secondary metabolites produced by fungi, pose a substantial worldwide health risk due to their widespread contamination of food commodities. Their toxicological effects include organ dysfunction, oxidative stress, and suppression of immune function. Emerging data indicate that circadian rhythm disruption is a critical but underrecognized mechanism contributing to mycotoxin-induced toxicity. This review summarizes current evidence showing that mycotoxins directly interfere with molecular circadian rhythm regulators. Specifically, deoxynivalenol markedly downregulates the expression of BMAL1, CLOCK, and CRY1/2 in hepatic cells. Similarly, zearalenone perturbs the temporal expression of BMAL1, PER2, and NR1D1 in testicular tissue, impairing testosterone biosynthesis. Furthermore, circadian rhythm disruption triggered by mycotoxins may initiate downstream pathological responses, including enhanced ROS generation and immune dysfunction through BMAL1-dependent regulation of PD-L1 expression. Importantly, a reciprocal feedback loop appears to exist wherein oxidative stress intensifies circadian rhythm disruption, which in turn promotes ROS accumulation and further immune impairment. These insights establish circadian rhythm disruption as a central mediator of mycotoxin-related toxicity and highlight BMAL1 as a potential therapeutic target. Nonetheless, experimental validation remains limited, and further mechanistic studies are required. We propose that circadian rhythm disruption may serve as an integrative node within the mycotoxin toxicity pathway, linking oxidative imbalance to immunosuppressive outcomes.

Název v anglickém jazyce

Circadian rhythm in mycotoxin-induced immunotoxicity: an emerging regulatory axis?

Popis výsledku anglicky

Mycotoxins, toxic secondary metabolites produced by fungi, pose a substantial worldwide health risk due to their widespread contamination of food commodities. Their toxicological effects include organ dysfunction, oxidative stress, and suppression of immune function. Emerging data indicate that circadian rhythm disruption is a critical but underrecognized mechanism contributing to mycotoxin-induced toxicity. This review summarizes current evidence showing that mycotoxins directly interfere with molecular circadian rhythm regulators. Specifically, deoxynivalenol markedly downregulates the expression of BMAL1, CLOCK, and CRY1/2 in hepatic cells. Similarly, zearalenone perturbs the temporal expression of BMAL1, PER2, and NR1D1 in testicular tissue, impairing testosterone biosynthesis. Furthermore, circadian rhythm disruption triggered by mycotoxins may initiate downstream pathological responses, including enhanced ROS generation and immune dysfunction through BMAL1-dependent regulation of PD-L1 expression. Importantly, a reciprocal feedback loop appears to exist wherein oxidative stress intensifies circadian rhythm disruption, which in turn promotes ROS accumulation and further immune impairment. These insights establish circadian rhythm disruption as a central mediator of mycotoxin-related toxicity and highlight BMAL1 as a potential therapeutic target. Nonetheless, experimental validation remains limited, and further mechanistic studies are required. We propose that circadian rhythm disruption may serve as an integrative node within the mycotoxin toxicity pathway, linking oxidative imbalance to immunosuppressive outcomes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/EH22_008%2F0004631" target="_blank" >EH22_008/0004631: Materiály a technologie pro udržitelný rozvoj</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

1663-9812

Svazek periodika

16

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

6

Strana od-do

1700863

Kód UT WoS článku

001608093000001

EID výsledku v databázi Scopus

2-s2.0-105021081190