Metronidazole (MTZ) is a widely used drug, but due to its many side effects, there is a growing trend today to use a minimum dose while maintaining high efficacy. One way to meet this demand is to reduce the size of the drug particles. A relatively new method of size reduction is attaching the drug molecules to a mesoporous carrier. In this paper, we studied the fixation of MTZ molecules on mesoporous silica carriers. The drug was immobilized on two mesoporous silica materials (Syloid, SBA-15) with the use of a variety of immersion techniques and solvents. The immobilized drug was subjected to physicochemical examinations (e.g., SEM, XPS, XRD, nitrogen uptake, DSC) and dissolution studies. A significantly higher immobilization was attained on SBA-15 than on a Syloid carrier. Among the processing parameters, the type of MTZ solvent had the highest influence on immobilization. Ultrasonic agitation had a lower but still significant impact, while the concentration of MTZ in the solution made no difference. Under optimal conditions, with the application of an ethyl acetate solution, the surface coverage on SBA-15 reached as much as 91%. The immobilized MTZ exhibited a ca. 10% faster dissolution rate as compared to the pure micron-sized drug particles.

In eukaryotic cells, phosphorus is assimilated and utilized primarily as phosphate (Pi). Pi homeostasis is mediated by transporters that have not yet been adequately characterized in green algae. This study reports on PHOSPHATE TRANSPORTER 4-7 (CrPHT4-7) from Chlamydomonas reinhardtii, a member of the PHT4 transporter family, which exhibits remarkable similarity to AtPHT4;4 from Arabidopsis (Arabidopsis thaliana), a chloroplastic ascorbate transporter. Using fluorescent protein tagging, we show that CrPHT4-7 resides in the chloroplast envelope membrane. Crpht4-7 mutants, generated by the CRISPR/Cas12a-mediated single-strand templated repair, show retarded growth, especially in high light, reduced ATP level, strong ascorbate accumulation, and diminished non-photochemical quenching in high light. On the other hand, total cellular phosphorous content was unaffected, and the phenotype of the Crpht4-7 mutants could not be alleviated by ample Pi supply. CrPHT4-7-overexpressing lines exhibit enhanced biomass accumulation under high light conditions in comparison with the wild-type strain. Expressing CrPHT4-7 in a yeast (Saccharomyces cerevisiae) strain lacking Pi transporters substantially recovered its slow growth phenotype, demonstrating that CrPHT4-7 transports Pi. Even though CrPHT4-7 shows a high degree of similarity to AtPHT4;4, it does not display any substantial ascorbate transport activity in yeast or intact algal cells. Thus, the results demonstrate that CrPHT4-7 functions as a chloroplastic Pi transporter essential for maintaining Pi homeostasis and photosynthesis in C. reinhardtii.

The author briefly summarizes the relationship between oxidative stress and changes in metal ion metabolism in pathological processes. Essential metal ions such as Ca, Mg, Fe, Cu, Zn, Se are essential in the living organisms, their metabolism and intracellular concentration are strictly regulated. Externally or intrinsically, altered metal ion metabolism can lead to metal ion accumulation or metal ion deficiency. Excess amounts of redox-active essential metals such as Fe, Cu, Co, Cr, Ni can induce free radicals under certain circumstances that cause inflammation, cell damage, and cancerous changes, although the molecular mechanism is still unclear in every detail. Changes in the metabolism of non-essential and non-variable valence metal ions also affect redox homeostasis. Despite the fact that each metal can react in a unique way and with different mechanisms, similar processes occur, where both metal deficiency and excessive metal induce oxidative stress. Antioxidant defense system is damaged, free radicals produced alter the redox balance, and redox homeostasis changed induces the production of cytokines and other transcription factors that affect the intracellular signaling pathways and affect the development of various diseases, including metabolic, cardiovascular, neurological diseases and cancer. Orv Hetil. 2019; 160(36): 1407–1416.

Metronidazole has been widely used topically and systemically for more than 50 years but data on its antioxidant properties are still incomplete, unclear and contradictory. Its antioxidant properties are primarily hypothesized based on in vivo results, therefore, studies have been performed to determine whether metronidazole has antioxidant activity in vitro. We used so-called global spectrophotometric and luminometric methods. Fe3+/Fe2+-reducing ability, hydrogen donor activity, hydroxyl radical scavenging property and lipid peroxidation inhibitory activity were investigated. Under the condition used, metronidazole has negligible iron-reducing ability and hydrogen donor activity. The hydroxyl radical scavenging capacity cannot be demonstrated. It acts as a pro-oxidant in the H2O2/.OH-microperoxidase-luminol system, but it can inhibit the induced lipid peroxidation. According to our results, metronidazole has not shown antioxidant activity in vitro but can affect redox homeostasis by a ROS-independent mechanism due to its non-direct antioxidant properties.