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Protective Action of Cannabidiol on Tiamulin Toxicity in Humans—In Vitro Study

2024, Pankowska, Eryka, Kończak, Oliwia, Żakowicz, Paula, Wojciechowicz, Tatiana, Gogulski, Maciej, Radko, Lidia

The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as tiamulin, leads to the appearance of residues in edible animal tissues. The use of natural substances of plant origin, extracted from hemp (Cannabis sativa L.), such as cannabidiol (CBD), is one of the solutions to minimize the negative effects of tiamulin. This study aimed to determine the effect of CBD on the cytotoxicity of tiamulin in humans. The cytotoxic activity of tiamulin and the effect of its mixtures with CBD were tested after 72 h exposure to three human cell lines: SH-SY5Y, HepG2 and HEK-293. Cytotoxic concentrations (IC50) of the tested drug and in combination with CBD were assessed using five biochemical endpoints: mitochondrial and lysosomal activity, proliferation, cell membrane integrity and effects on DNA synthesis. Oxidative stress, cell death and cellular morphology were also assessed. The nature of the interaction between the veterinary drug and CBD was assessed using the combination index. The long-term effect of tiamulin inhibited lysosomal (SH-SY5SY) and mitochondrial (HepG2) activity and DNA synthesis (HEK-293). IC50 values for tiamulin ranged from 2.1 to >200 µg/mL (SH-SY5SY), 13.9 to 39.5 µg/mL (HepG2) and 8.5 to 76.9 µg/mL (HEK-293). IC50 values for the drug/CBD mixtures were higher. Reduced levels of oxidative stress, apoptosis and changes in cell morphology were demonstrated after exposure to the mixtures. Interactions between the veterinary drug and CBD showed a concentration-dependent nature of tiamulin in cell culture, ranging from antagonistic (low concentrations) to synergistic effects at high drug concentrations. The increased risk to human health associated with the presence of the veterinary drug in food products and the protective nature of CBD use underline the importance of these studies in food toxicology and require further investigation.

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Neurotoxicological Effects of Some Mycotoxins on Humans Health and Methods of Neuroprotection

2025, Kuć-Szymanek, Aleksandra, Kubik-Machura, Daria, Kościelecka, Klaudia, Męcik-Kronenberg, Tomasz, Radko, Lidia

Food contamination with mycotoxin-producing fungi increases the risk of many diseases, including neurological diseases closely related to the neurotoxicity of these toxins. Based on the latest literature data, we presented the association of common Fusarium mycotoxins with neurological diseases. Articles from 2001 to 2024 were analyzed. The mechanisms underlying the neurotoxicity of the described mycotoxins were presented. They are mainly related to the increase in oxidative stress in neuronal cells, which leads to higher levels of pro-inflammatory cytokines as IL-1β, IL-6 and TNF-α, enzymatic activity as GST, GPx, CAT and SOD and neurotransmitter dysfunction (5-HT, serotonin, dopamine and GABA). At the end of the article, based on the literature data, we attempted to present ways to mitigate mycotoxin neurotoxicity using mainly natural substances of plant origin. The data in this review focus on the Fusarium mycotoxins most frequently found in food and will be useful as comparative information for future studies. It is important to conduct further studies to mitigate the neurotoxic effects of Fusarium mycotoxins in order to reduce the development of diseases of the nervous system.