Zinc Deficiency Blunts the Effectiveness of Antidepressants in the Olfactory Bulbectomy Model of Depression in Rats.

Currently used antidepressants do not always provide the desired results, and many patients suffer from treatment-resistant depression. Clinical studies suggest that zinc deficiency (ZnD) may be an important risk factor for depression and might blunt the effect of antidepressants. This study aimed to examine whether ZnD might blunt the effectiveness of antidepressants in the olfactory bulbectomy model (OB) of depression in rats. For this purpose, rats were subjected to the OB model, fed a zinc-deficient diet (3 mg Zn/kg) for 3 weeks, and finally treated with escitalopram (Esc), venlafaxine (Ven) 10 mg/kg, i.p., or combined Esc/Ven (1 mg/kg, i.p.) with zinc (5 mg/kg) for another 3 weeks. Open field (OFT), forced swim (FST), and sucrose intake (SIT) tests were used to evaluate depressive-like behavioral changes. In addition, serum, intracellular, and synaptic Zn concentrations and the level of zinc transporter (ZnT) proteins were analyzed. The OB + ZnD model induced hyperactivity in rats in the OFT, increased immobility time in the FST, and anhedonia in the SIT. Chronic treatment with Esc reduced immobility time in the FST in the OB + ZnD model. Esc/Ven +Zn increased sucrose intake in rats from the OB + ZnD group. The OB + ZnD decreased serum zinc levels and intracellular and synaptic Zn concentration in the prefrontal cortex (PFC) and cerebellum. These changes were normalized by chronic administration of Esc/Ven +Zn. Moreover, OB + ZnD decreased levels of the ZnT1 protein in the PFC and Hp and ZnT3 in Hp. Chronic administration of antidepressants did not alter the levels of ZnT proteins. The OB + ZnD model induces more depressive-like effects than either model alone. Our results show that ZnD may induce drug resistance in rats. Normalizing serum or brain zinc concentration is insufficient to reverse behavioral abnormalities caused by the OB + ZnD model. However, zinc supplementation might improve the effectiveness of antidepressants in reversing particular depression symptoms.

Yerba Mate as a Source of Elements and Bioactive Compounds with Antioxidant Activity.

Ilex paraguariensis (yerba mate) is a plant species of the holly genus Ilex native to South America from the family Aquifoliaceae and is used for the production of yerba mate infusion. The leaves of the plant are steeped in hot water to make a beverage known as mate. The present study aimed to quantify and compare the content of selected elements in dried leaves and stems of I. paraguariensis (originating from Paraguay, Argentina, and Brazil) available in the market in Poland and determine the amount of these elements and bioactive compounds that pass into the infusion prepared from them. The contents of the following antioxidant compounds were assessed: neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, 4-feruloylquinic acid, isochlorogenic acid, rutoside, astragalin, caffeine, and indole derivatives. All the tested samples showed the presence of elements such as magnesium, zinc, copper, iron, and manganese. The highest antioxidant activity was determined for infusion prepared from yerba mate samples from Brazil. Drinking approximately 1 L of the infusion a day will partially cover the daily requirement of these elements and bioactive compounds. The highest content of organic compounds with antioxidant properties (phenolic compounds and caffeine) was found in yerba mate infusions from Brazil.

Antioxidant-Rich Natural Raw Materials in the Prevention and Treatment of Selected Oral Cavity and Periodontal Diseases.

Antioxidant-rich natural raw materials have been used for thousands of years in traditional medicine. In the past decade, there has been increasing interest in naturotherapy, which is a practice of using products with a natural origin. Natural products can be effective in the treatment and prevention of oral and dental diseases, among others. Such raw materials used in dentistry are characterized by antioxidant, anti-inflammatory, antibacterial, antiviral, antiedematous, astringent, anticoagulant, dehydrating, vitaminizing, and-above all-regenerative properties. Reports have shown that a relationship exists between oral diseases and the qualitative and quantitative composition of the microbiota colonizing the oral cavity. This review aimed to analyze the studies focusing on the microbiome colonizing the oral cavity in the context of using natural raw materials especially herbs, plant extracts, and isolated biologically active compounds as agents in the prevention and treatment of oral and periodontal diseases such as dental caries as well as mucosal changes associated with salivary secretion disorder. The present work discusses selected plant ingredients exhibiting an antioxidant activity with potential for the treatment of selected oral cavity and periodontal diseases.

Photodegradation of Bexarotene and Its Implication for Cytotoxicity.

A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO2 or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (p < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration.

Disinfectants Used in Stomatology and SARS-CoV-2 Infection.

Effective disinfection is a basic procedure in medical facilities, including those conducting dental surgeries, where treatments for tissue discontinuity are also performed, as it is an important element of infection prevention. Disinfectants used in dentistry and dental and maxillofacial surgery include both inorganic (hydrogen peroxide, sodium chlorite-hypochlorite) and organic compounds (ethanol, isopropanol, peracetic acid, chlorhexidine, eugenol). Various mechanisms of action of disinfectants have been reported, which include destruction of the structure of bacterial and fungal cell membranes; damage of nucleic acids; denaturation of proteins, which in turn causes inhibition of enzyme activity; loss of cell membrane integrity; and decomposition of cell components. This article discusses the most important examples of substances used as disinfectants in dentistry and presents the mechanisms of their action with particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The search was conducted in ScienceDirect, PubMed, and Scopus databases. The interest of scientists in the use of disinfectants in dental practice is constantly growing, which results in the increasing number of publications on disinfection, sterilization, and asepsis. Many disinfectants often possess several of the abovementioned mechanisms of action. In addition, disinfectant preparations used in dental practice either contain one compound or are frequently a mixture of active compounds, which increases their range and effectiveness of antimicrobial action. Currently available information on disinfectants that can be used to prevent SARS-CoV-2 infection in dental practices was summarized.

Mycelial culture extracts of selected wood-decay mushrooms as a source of skin-protecting factors.

OBJECTIVES: This study analyzed the content of substances with cosmetologic properties in the extracts obtained from the mycelial cultures of Ganoderma applanatum, Laetiporus sulphureus, and Trametes versicolor. The effect of these extracts on the inhibition of tyrosinase and hyaluronidase was determined, and their values of sun protection factor (SPF) were calculated. RESULTS: The total amount of phenolic acids in the extracts ranged from 2.69 (G. applanatum) to 10.30 mg/100 g dry weight (T. versicolor). The total amount of sterols was estimated at 48.40 (T. versicolor) to 201.04 mg/100 g dry weight (L. sulphureus), and that of indoles at 2.90 (G. applanatum) to 16.74 mg/100 dry weight (L. sulphureus). Kojic acid was determined in the extracts of L. sulphureus and G. applanatum. It was observed that L. sulphureus extract caused dose-dependent inhibition of hyaluronidase, while all the extracts inhibited tyrosinase. The extract of G. applanatum exhibited an SPF value of ~ 9. CONCLUSIONS: The results showed that the mycelial cultures of the studied species may be used as an alternative source of substances used in cosmetology.

Photostability Testing of a Third-Generation Retinoid-Tazarotene in the Presence of UV Absorbers.

Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography-tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2H-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. In silico studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2H-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations.

Feasibility of the use of Lentinula edodes mycelium in terbinafine remediation.

A detailed understanding of the fate of xenobiotics introduced into the environment and the mechanisms involved in their biotransformation, biodegradation, and biosorption is essential to improve the efficiency of remediation techniques. Mycoremediation is a form of bioremediation technique that has become increasingly popular in recent years as fungi are known to produce various effective extracellular enzymes that have the potential to neutralize a wide variety of xenobiotics released into the environment. Hence, mycoremediation appears to be a promising technique for the removal of a wide array of toxins and pharmaceutical residues from a damaged environment and wastewater. This study primarily aimed to investigate whether white-rot fungus (Lentinula edodes) can be utilized for the bioremediation of common antifungal agent terbinafine, which is mainly available in the market as powder or cream. The cultures of L. edodes were cultivated in the medium containing terbinafine powder or terbinafine 1% cream, each at a final concentration of 0.1 mg mL-1. The addition of terbinafine in powder form have a negative effect on biomass growth (p < 0.05). The total amount of terbinafine in the dry weight of mycelium after culture was estimated to be 7.63 ± 0.45 mg and 12.52 ± 2.46 mg for powder and cream samples, respectively. In addition, there were no traces of terbinafine in any of the samples of medium used for culturing L. edodes after the experimental duration period. The biodegradation products of terbinafine were identified for the first time using UPLC/MS/MS. The biodegradation of terbinafine resulted in the loss of 1-naphthylmethanol, which occurred via oxidative deamination, N-demethylation, or tert-butyl group hydroxylation. The results of the study demonstrate that L. edodes mycelium can be effectively used for the remediation of terbinafine.

Photostability of Topical Agents Applied to the Skin: A Review.

Topical treatment modalities have multiple advantages starting with the convenient application and non-invasive treatment and ending with the reduction of the risk of the systemic side effects. Active pharmaceutical substances must reach the desired concentration at the target site in order to produce a particular therapeutic effect. In contrast to other dosage forms topical agents applied to the skin may also be susceptible to photodegradation after application. That is why the knowledge of the susceptibility of these topical drugs to UV irradiation, which may contribute to their degradation or changes in chemical structure, is very important. Active pharmaceutical substances used in dermatology may differ both in chemical structure and photostability. Furthermore, various factors-such as light intensity and wavelength, pH, temperature, concentration-can influence the photodegradation process, which is reflected in particular in kinetics of photodegradation of active pharmaceutical substances as well as both the quantitative and qualitative composition of by-products. The aim of this study was to conduct a systematic review of the photostability of dermatological drugs, as well as of other substances commonly applied topically. The photostability of glucocorticosteroids, retinoids, and antifungal drugs as well as non-steroidal anti-inflammatory drugs applied topically and selected UV-filters have been discussed. Furthermore, the impact of photoinstability on the effectiveness of pharmacotherapy and some photostabilization strategies have been also included.

Discovery of Novel UV-Filters with Favorable Safety Profiles in the 5-Arylideneimidazolidine-2,4-dione Derivatives Group.

Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,2'-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,2'-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo- imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPFin vitro of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 µM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model.

Mycoremediation of azole antifungal agents using in vitro cultures of Lentinula edodes.

Azole antifungal agents are widely used as active ingredients in antifungal pharmaceuticals and agricultural fungicides. An increase in the use of azole antifungals has resulted in an increase in the concentration of these compounds in wastewater and surface water, with potential implications for agriculture. In the present study, bifonazole (BIF) and clotrimazole (CTZ) were selected for investigation because of their widespread use in topical formulations and persistence in the environment. The mycoremediation capacity of BIF and CTZ by mycelia of Lentinula edodes in in vitro culture was evaluated. The main aim of this study was to identify the presumable biodegradation products of the investigated active pharmaceutical substances using the LC/MS/MS method. For this purpose, the media were enriched with the following active pharmaceutical ingredients selected for this study: BIF powder, CTZ powder, and BIF cream, each of them at the same concentration of 0.1 mg/mL. Subsequently, thin-layer chromatography coupled with densitometry was used to evaluate the content of BIF and CTZ in mycelium from in vitro cultures of L. edodes. The degradation process was found to affect primarily the imidazole moiety of both investigated compounds. In addition, the amounts of undegraded investigated compounds were found to be 4.98, 9.26, and 4.56 mg/g dry weight for BIF powder, CTZ powder, and BIF cream, respectively. Therefore, the findings of this study revealed that L. edodes could be considered for remediation of pollution caused by azole antifungal agents.

Photostability of Terbinafine Under UVA Irradiation: The Effect of UV Absorbers.

The photostability of drugs administered topically on unprotected skin is a complex phenomenon that could be connected with the loss of activity or, rather rarely, the occurrence of toxic degradation products. In this study, an in-depth investigation of the photostability of terbinafine, in both solutions and formulations, was conducted, taking into account the presence of UV absorbers such as TiO2 , ZnO, avobenzone, 3-(4-methylbenzylidene)camphor, octocrylene, benzophenone-1 and benzophenone-2. The clear photocatalytic degradation of terbinafine in ethanol solution was observed in the presence of TiO2 and/or ZnO. In other cases, terbinafine was stable, with the exception of, in the presence of octocrylene. The presumed degradation products of terbinafine were identified for the first time using LC/MS/MS, and transformation pathways were proposed. In the case of a cream formulation, the percentage of initial terbinafine content was almost unchanged in the presence of the UV absorbers benzophenone-1, benzophenone-2 and 3-(4-methylbenzylidene)camphor. In vitro cytotoxicity risk assessment of terbinafine based on photostability under UVA irradiation was evaluated using the human skin fibroblast BJ (ATCC® CRL-2522™), and this showed no statistically significant difference in cell viability for all samples analyzed.