Cardiotoxicity of pyrethroids: molecular mechanisms and therapeutic options for acute and long-term toxicity

Autor: Leisiane P. Marques, Julliane V. Joviano-Santos, Diego S. Souza, A. Santos-Miranda, D. Roman-Campos
Rok vydání: 2022
Předmět:
Zdroj: Biochemical Society Transactions. 50:1737-1751
ISSN: 1470-8752
0300-5127
DOI: 10.1042/bst20220593
Popis: Pyrethroids (PY) are synthetic pesticides used in many applications ranging from large-scale agriculture to household maintenance. Their classical mechanisms of action are associated with binding to the sodium channel of insect neurons, disrupting its inactivation, ensuring their use as insecticides. However, PY can also lead to toxicity in vertebrates, including humans. In most toxicological studies, the impact of PY on heart function is neglected. Acute exposure to a high dose of PY causes enhancement of the late sodium current (INaL), which impairs the action potential waveform and can cause severe cardiac arrhythmias. Moreover, long-term, low-dose exposure to PY displays oxidative stress in the heart, which could induce tissue remodeling and impairment. Isolated and preliminary evidence supports that, for acute exposure to PY, an antiarrhythmic therapy with ranolazine (an INaL blocker), can be a promising therapeutic approach. Besides, heart tissue remodeling associated with low doses and long-term exposure to PY seems to benefit from antioxidant therapy. Despite significant leaps in understanding the mechanical details of PY intoxication, currently, few studies are focusing on the heart. In this review, we present what is known and what are the gaps in the field of cardiotoxicity induced by PY.
Databáze: OpenAIRE