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Toxicity of penicillic acid for rat alveolar macrophages in vitro
Abstract:
Penicillic acid (PA) is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium. This mycotoxin is toxic in experimental animals and has also been reported to be carcinogenic. The cytotoxicity of penicillic acid was studied in rat alveolar macrophages (AM) in vitro. The effects of penicillic acid on membrane integrity were studied by measuring cell volume changes and 51Cr release. There was significant 51Cr release after 2 hr exposure to 1.0 mM penicillic acid, but not after 1 hr exposure. There was a significant decrease in adenosine triphosphate (ATP) in cell cultures exposed to 1.0 mM penicillic acid for 4 hr. Inhibition of the incorporation of [3H]leucine into protein was both dose- and time-dependent and protein synthesis was inhibited significantly after 2 hr exposure to greater than or equal to 0.1 mM penicillic acid. RNA synthesis was inhibited to a lesser extent than protein synthesis. Although there was a significant inhibition of RNA synthesis at 1.0 mM PA after 4 hr, there was no inhibition of RNA synthesis even after 4 hr at any concentration less than 1.0 mM. The ED50 dose after 2 hr exposure was 0.18 and 0.60 mM for protein and RNA synthesis, respectively. There was significant inhibition of phagocytosis after 2 hr exposure at greater than or equal to 0.3 mM penicillic acid and the ED50 for phagocytosis was 0.09 mM. Thus phagocytosis was more sensitive to the toxic effects of penicillic acid than any other cellular process studied. The results reported in this study are similar to those observed for patulin in an earlier study from our laboratory except that patulin was generally more toxic to alveolar macrophages than penicillic acid. The data demonstrate that penicillic acid is toxic to rat alveolar macrophages in vitro and suggest the possibility of a respiratory hazard to agricultural workers exposed to contaminated grain.
Insights
Penicillic acid (PA) is a toxic mycotoxin that harms rat alveolar macrophages by inhibiting protein synthesis and phagocytosis. Exposure to contaminated grain may pose a respiratory risk to agricultural workers.
Area of Science:
- Toxicology
- Cell Biology
- Mycotoxicology
Background:
- Penicillic acid (PA) is a toxic and carcinogenic polyketide mycotoxin.
- It is produced by Aspergillus and Penicillium species.
- PA poses potential health risks, particularly respiratory hazards.
Purpose of the Study:
- To investigate the in vitro cytotoxicity of penicillic acid (PA) on rat alveolar macrophages (AM).
- To assess the effects of PA on cellular processes including membrane integrity, ATP levels, protein synthesis, RNA synthesis, and phagocytosis.
Main Methods:
- Rat alveolar macrophages (AM) were exposed to varying concentrations of penicillic acid (PA).
- Cellular effects were measured by 51Cr release, ATP levels, [3H]leucine incorporation, RNA synthesis, and phagocytosis assays.
- Dose-response and time-course experiments were conducted.
Main Results:
- Penicillic acid (PA) significantly reduced membrane integrity (51Cr release) and ATP levels.
- Protein synthesis was inhibited dose- and time-dependently, with significant effects at ≥0.1 mM after 2 hr (ED50 = 0.18 mM).
- Phagocytosis was most sensitive, with significant inhibition at ≥0.3 mM (ED50 = 0.09 mM), while RNA synthesis was less affected.
Conclusions:
- Penicillic acid (PA) exhibits significant cytotoxicity to rat alveolar macrophages (AM) in vitro.
- Phagocytosis is the most sensitive cellular process to PA toxicity among those studied.
- Occupational exposure to PA-contaminated grain may present a respiratory hazard to agricultural workers.