Nejvíce citovaný článek - PubMed ID 36212465
Platinum-based drug-induced depletion of amino acids in the kidneys and liver
BACKGROUND: Bovine mastitis is one of the main causes of reduced production in dairy cows. The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus, whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses. Therefore, it is important to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains. In this study, novel selenium-tellurium based nanoparticles (SeTeNPs) were synthesized and characterized. Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model. A total of 10 heifers were divided into experimental and control groups (5 animals each). After intramammary infection with methicillin resistant S. aureus (MRSA) and the development of clinical signs of mastitis, a dose of SeTeNPs was administered to all quarters in the experimental group. RESULTS: Based on in vitro tests, the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te, respectively, was used for application into the mammary gland. Three days after SeTeNPs administration, MRSA counts in the experimental group showed a significant reduction (P < 0.01) compared to the control group. The inhibitory effect observed within the in vitro experiments was thus confirmed, resulting in the suppression of infection in animals. Moreover, the superior biocompatibility of SeTeNPs in the organism was demonstrated, as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application, i.e., mammary gland, compared to the control group (P > 0.05). Additionally, the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected, indicating that the nanoparticles had no adverse effects on the organism. CONCLUSIONS: Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the presence of resistant bacteria. However, the current study is limited by its small sample size, making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs. Therefore, further research with a larger sample size is needed to validate these results.
- Klíčová slova
- Antibacterial, Biocompatibility, Heifer, Intramammary, MRSA, Mammary gland, Nanomaterial, Resistance, SeTe,
- Publikační typ
- časopisecké články MeSH
The combination of in ovo and ex ovo chorioallantoic membrane (CAM) assay provides an excellent platform which extends its relevance in studying carcinogenesis to the field of screening of anticancer activity of platinum nanoparticles (PtNPs) and further study of the amino acids' fluctuations in liver and brain. PtNPs are promising candidates for replacing cisplatin (CDDP); however, insufficient data of their antitumor efficiency and activity on the cancer-related amino acid metabolism are available, and the assessment of the in vivo performance has barely scratched the surface. Herein, we used CAM assay as in vivo model for screening of novel therapeutic modalities, and we conducted a comparative study of the effects of CDDP and polyvinylpyrrolidone coated PtNPs on MDA-MB-231 breast cancer xenograft. PtNPs showed a higher efficiency to inhibit the tumor growth and metastasis compared to CDDP. The amino acids profiling in the MDA-MB-231 cells revealed that the PtNPs had an overall depleting effect on the amino acids content. Noteworthy, more side effects to amino acid metabolism were deduced from the depletion of the amino acids in tumor, brain, and liver upon CDDP treatment. Different sets of enzymes of the tricarboxylic acid (TCA) cycle were targeted by PtNPs and CDDP, and while mRNA encoding multiple enzymes was downregulated by PtNPs, the treatment with CDDP affected only two TCA enzymes, indicating a different mechanism of action. Taken together, CAM assay represents and invaluable model, demonstrating the PtNPs capability of repressing angiogenesis, decrease amino acid contents and disrupt the TCA cycle.
- Klíčová slova
- Amino acids metabolism, Breast cancer, CAM assay, Cisplatin, Platinum nanoparticles, TCA cycle,
- Publikační typ
- časopisecké články MeSH