Commercial Name Research Articles

Marketing antibiotics as vaccines? Analyzing the successful marketing of a pharmaceutical innovation: the case of tulathromycin in veterinary medicine

This article aims to explain the success of tulathromycin in the cattle and pig industry by tracing the ‘social life’ of this antibiotic. To do so, it draws on interview data with veterinarians working in the pharmaceutical industry, observations from training sessions conducted by them, and data from professional journals. The article demonstrates that tulathromycin’s success primarily stems from its unique properties as a long-acting macrolide antibiotic, positioning it as an innovative solution in the veterinary market. By providing immediate and prolonged protection with a single injection, it addresses organizational challenges in the cattle and pig sectors. It thus serves as a ‘quick fix’ for disease control in intensive farming systems and appears, as such, more suitable than vaccination. Its presentation and commercial name, Draxxin, is reminiscent of “vaccine”, which contributes to the confusion about its nature and plays a key role in its widespread adoption.

Human PapillomaVirus Vaccine Uptake: Attitudes and Practices Among Moroccan Physicians.

In Morocco, cervical cancer is a serious public health problem with an estimated number of 2165 new cases and 1199 deaths in 2020. The human papillomavirus (HPV) vaccine has been available in Morocco since 2008. Few data are available on physicians' practices and attitudes toward HPV vaccine. Hence, this study aims to evaluate physicians' awareness and practice towards HPV vaccine and to highlight the main factors affecting physicians' recommendation of this vaccine in Morocco. We have carried out a structured interviewer-administered questionnaire with 500 physicians in different Moroccan regions between March 2019 and March 2020. This study showed an insufficient level of awareness of the two most common types of HPV associated with cervical cancer (36.6%). The rate of HPV vaccine recommendation did not exceed 16.6%. However, more than 63% of participants who were aware of HPV vaccine were willing to recommend it for their future eligible patients. Age (p value < 0.01), sector of activity (p value < 0.01), awareness of the two most common types of HPV associated with genital warts (p value = 0.02), of the vaccine schedules (p value = 0.03), and of the commercial name of this vaccine (p value < 0.01), were significant factors influencing physicians' recommendation of HPV vaccine. Our results showed that, older age (above 51years old) was associated with negative attitude towards the recommendation of this vaccine (OR: 0.17, 0.06-0.46 CI 95%). Practice in public sector was positively associated with recommendation of HPV vaccine (OR: 7.54, 3.38-16.80 CI 95%). Who were aware of the two most common types of HPV associated with genital warts were more likely to recommend HPV vaccine (OR: 3.36, 1.31-8.65 CI 95%). In the same line, participants, who were also more likely to recommend the vaccine, were those who were aware of HPV vaccine schedules (OR: 6.07, 3.51-10.50 IC 95%); participants who were aware of the commercial name of the HPV vaccine were more likely to recommend the vaccine (OR: 10.04, 5.02-20.09 IC 95%). Indeed, raising physicians' awareness is urgently needed to improve HPV vaccine coverage within Moroccan population.

Asbestos: Communicating the Health Issues Derived from Fibrous Minerals to Society

Asbestos, also known by its commercial name “amianthus”, has been widely used in various industries due to its unique properties. However, the extensive use of asbestos has had serious consequences for human health, most notably asbestosis, an irreversible chronic lung disease. Asbestosis increases the risk of lung cancer and malignant mesothelioma, both of which are fatal. Applied sciences such as microscopy (optical and scanning electron microscopy) and geochemistry have been fundamental in characterizing the mineral fibers of asbestos to understand its role in human health. We previously used these techniques to characterize these fibers; in this study, we explored the issues associated with asbestos and asbestosis, as well as the challenges facing science communication strategies in effectively informing society and workers about these risks. The lack of scientific culture, in general, has led to a lack of public awareness of the risks of asbestos. As such, effective communication and outreach plans and strategies, including the visualization of the fibers to demonstrate why problems arise if inhaled, must be implemented to address these challenges. Educational campaigns, guidelines, and plans that are informative and actionable, teaching workers, communities, and the public about the risks of asbestos are crucial. A general knowledge of mineralogy and geochemistry is needed, and providing and disseminating proper scientific communication may help to close the knowledge gap. We use examples and experience from Spain and Italy to illustrate this matter, as we have been working on the characterization of ultramafic complexes in these countries for more than ten years. Additionally, because these countries have strict laws for asbestos-containing materials, they are currently involved in retiring and demolishing buildings and infrastructure that contain asbestos.

METROLOGICAL ANALYSIS OF THE IMPACT OF THE ARRANGEMENT OF MODELS ON THE 3D PRINTER PLATFORM ON THE DIMENSIONAL ACCURACY OF MODELS MANUFACTURED USING PHOTO-CURING TECHNOLOGY - PJM

The paper presents the results of metrological tests and measurements of dimensional accuracy of models manufactured using the photo-curing additive technology of POLYJET MATRIX - PJM. The material from which the samples were manufactured was a liquid polymer resin with the commercial name MED610, which is characterized by a high degree of biocompatibility, which increases the validity of the research in medical and dental applications. The key parameter considered was the location of digital CAD models in selected places of the virtual building platform and it influence of dimensional accuracy. The research results showed a clear impact of the arrangement of models on the building platform on the accuracy of the produced models, both in terms of external and internal diameters.

Stability Indicating RP-HPLC Method Development and Validation for Quantification of Favipiravir and its Related Substances.

Background: Favipiravir is an influenza antiviral medication. DEM Avigan is the commercial name for a pyrazine carboxamide derivative. Aim: According to the guidelines framed by ICH - International Council for Harmonisation, the present method was developed and validated for the system suitability, specificity, linearity, precision, limit of quantification and limit of detection, accuracy, &amp; robustness. Results: All the results obtained were within the acceptable range. This method was used to better separate the peaks of Favipiravir and its three impurities. The retention times and squared correlation coefficient values of Impurity-1, Impurity-2, Favipiravir &amp; Impurity-3 were obtained at 1.998, 3.223, 4.438 &amp; 7.052 min and 0.9993, 0.9995, 0.9998 &amp; 0.9997 respectively. Conclusion: Thus, the results show that the suggested RP-HPLC method for separating three contaminants with Favipiravir was effective and may be utilised in routine pharmaceutical analysis and quality control. Forced degradation was carried out under different stress conditions thus proving as stability indicating as per ICH guidelines.

Environmental fluoxetine promotes skin cell proliferation and wound healing

This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and personal care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and a human keratinocyte cell line, we show that exposure to environmental FLX promotes wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. Using several –omics and pharmaceutical approaches, we demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases linked to the MAPK pathway. Consistent with this, phosphoproteomic analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. Treatment of skin biopsies and keratinocytes with ketanserin, a serotonin receptor antagonist, reversed the increase in wound closure observed upon exposure. These findings collectively show that exposure to environmental FLX promotes wound healing through modulating serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results justify a transition from the study of behavioural effects of environmental FLX in aquatic animals to the investigation of effects of exposure on wound healing in aquatic and terrestrial animals, including direct impacts on human health.

Clarifying to whom, where, and when payments are made : Recommendations from the ERPB Working Group on Transparency for Retail Payment End Users

It has become increasingly difficult for consumers to identify to whom, where, and when they have made payment transactions, as the descriptions provided on account statements do not always match the expectations of the consumer. Given that multiple actors in the payment chain can influence the information provided to the consumer, this problem can only be addressed with the involvement of multiple stakeholders. This paper discusses the recommendations made by the working group established by the Euro Retail Payments Board (ERPB) to address this issue. As regards the name of the party to whom payment has been made, the working group recommended that the commercial trade name of the payee (defined as the name used by the merchant to identify itself to the consumer) should be used along the entire payments chain. Regarding the where element, the working group recommended that the account statement should indicate the precise geographical location of the transaction. In the case of online commerce, the commercial trade name displayed on the website, or the commercial trade name of the payee’s online platform should be mentioned. Related to the when element, the working group recommended that the account statement should indicate clearly the date and time of the transaction as it would be known by the consumer. The working group called upon all actors involved to create and maintain quality transaction data and to ensure that the underlying technical standards being used are capable of supporting the collection, preservation and safe transmission of the data required by the consumer. The industry was expected to implement these voluntary recommendations by June 2024, but although progress has been made, the overall progress seems to be lagging slightly as the various stakeholders are addressing the issue in isolation. In the meantime, the European Commission has adopted some of the working group’s recommendations into proposed new payments legislation.

Estimating the Cowper–Symonds Parameters for High-Strength Steel Using DIC Combined with Integral Measures of Deviation

Cowper–Symonds parameters were estimated for the complex-phase high-strength steel with a commercial name of SZBS800. The parameter estimation was based on a series of conventional tensile tests and unconventional high-strain rate experiments. The parameters were estimated using a reverse engineering approach. LS-Dyna was used for numerical simulations, and the material’s response was modelled using a piece-wise linear plasticity model with a visco-plastic formulation of the Cowper–Symonds material model. A multi-criteria cost function was defined and applied to obtain a response function for the parameters p and C. The cost function was modelled with a response surface, and the optimal parameters were estimated using a real-valued genetic algorithm. The main novelty and innovation of this article is the definition of a cost function that measures a deviation between the deformed geometry of the flat plate-like specimens and the results of the numerical simulations. The results are compared to the relevant literature. A critical evaluation of our results and references is another novelty of this article.

Optimizing vertical farm cultivation of Cichorium spinosum L.: White Light's influence and nutrition management

The objective of this study was to examine the integration of a wild leafy vegetable, Cichorium spinosum L., in vertical farms. This research comprises two experiments focusing on different “white” light products and nutrient solutions. During both experiments, the temperature varied between 25 and 28 °C, relative humidity ranged from 50 to 70 %, carbon dioxide was at 450 ppm, and light intensity was set at 300 μmol m−2 s−1 respectively. In the lighting experiment, the three spectra used had the commercial names Neutral, Full and a SunLike™, and their spectral composition (blue:green:red:far-red) were 14:32:43:10, 16:36:40:8, and 21:34:36:7 respectively. The photoperiod was set to 12 h and the plant density was 50 plants m−2. Results showed no significant impact on agronomical parameters and leaf anatomy. The stomatal length and width decreased as the red:blue ratio of the light sources decreased, being greater in the Neutral treatment (red:blue ratio of 3.1) compared to the Full and SunLike™ (red:blue ratios of 2.5 and 1.7 respectively). Based on these results the preferable “white light” product was the one with the highest efficiency and lowest market price at the time of the experiment. In the nutrient solution experiment, the agronomical and nutritional attributes of stamnagathi plants supplied with a control nutrient solution, “N10-Fe15” were compared to plants cultivated under limited nitrogen, “N4-Fe15” and elevated iron, “N10-Fe48”, EC was 1.5 ds m−1, and pH was 5.6–6.5. The experiment simulated commercial practices by increasing the photoperiod to 15 h and plant density to 100 plants per square meter. The results did not demonstrate significant effect of the nutrient solution differences on the agronomical characteristics except from a decrease in total Kjeldahl nitrogen under limited nitrogen conditions. Notably, leaf tissue phosphorus content increased under elevated iron conditions. The nitrate content remained within safe for consumption thresholds for all treatments. Based on these results, stamnagathi can be integrated in vertical farms under limited nitrogen conditions. Stamnagathi's resilience to elevated iron in the nutrient solution demonstrated its potential for future biofortification experiments.

Russian elements in the ergonymy of intra-urban objects in Moscow

The article presents a fragment of a study examining the ergonymy of intra-urban objects in Moscow. The research focuses on ergonyms created on the basis of the Russian language. The study aims to find out what names of commercial enterprises are more attractive to city residents, which of them provoke positive, neutral, or negative emotions. The material for the study included the names of commercial enterprises in Moscow formed with the techniques of retrohybridisation, quasi-naming, anti-orthography, superimposition of words, and allusion. During the study, 2700 names of commercial enterprises located on the signs, bracket panels, and in the shop windows of establishments in the main streets of Moscow were collected. The selected ergonyms were classified according to their formation methods. A survey involving 90 respondents of different ages and educational backgrounds was conducted as well. The data obtained during the survey were processed using statistical analysis. Based on the experimental results, the study revealed that ergonyms with letters from the pre-revolutionary script had positive evaluations more often. Also, they were the most memorable. The largest number of negative evaluations was given to the names with a deliberate distortion of the Russian orthographic norm. Drawing on the data obtained, the paper formulates recommendations to those who create commercial enterprise names aimed at different age groups of consumers. The results of the work can be used in linguodidactics, for example, in the process of teaching Russian as a foreign language.

The Clinical Utility of Botulinum Toxin in the Field of Otolaryngology

Botulinum toxin, originally identified in relation to botulism, has evolved from being considered a perilous pathogen to an invaluable therapeutic agent. First utilized by Alan Scott in 1977 to treat strabismus under the commercial name, Oculinum, the toxin received Food and Drug Administration approval in 1989 and was subsequently rebranded as Botox. Its clinical applications have expanded notably, especially in the field of otolaryngology, proving effective in managing conditions such as spasmodic dysphonia, essential vocal tremor, and chronic salivary gland disorders. Moreover, botulinum toxin has shown promising results in treating persistent chronic rhinitis, objective tinnitus, and synkinesis following facial palsy, significantly improving involuntary facial movements. This paper details the diverse applications and methodologies of botulinum toxin across various ENT disorders, illustrating its growing scope and significance in medical practice.

Authentication of sushi and sashimi products from northeastern Pará, coastal Amazon, by DNA barcoding reveals commercial frauds and potential threats to human health and environment

The Japanese cuisine has become a huge success in Brazil over the last years, but little is known about the fisheries resources commercialized to supply this specific market. In the present study, we carried out the first molecular characterization of sushi and sashimi products available in northeastern Pará, coastal Amazon, in order to infer what species have been actually exploited in this trade. We sequenced two mitochondrial DNA regions from 172 samples (138 of fish and 34 of shrimp-derived products) that were divided into 28 haplotypes. The comparative analyses with public DNA barcode databases revealed eight species of fish and three of shrimps among the samples, including cases of commercial frauds. For instance, Ruvettus pretiosus and Lepidocybium flavobrunneum were traded as “anchova” (bluefish), a valid and specific commercial name of Pomatomus saltatrix. Both species can cause gastrointestinal issues, which has led to restrictions on their sale in several countries. All commercialized shrimp-derived products were labeled as “camarão” (shrimp), as generic trade name that could not be applied to identify each species. Furthermore, potentially threatened species have also been recorded in the commercial products, such as Salmo salar and Cynoscion acoupa, classified as “nearly threatened” and “vulnerable”, respectively. The later, popularly known as “pescada-amarela” (acoupa weakfish) has been commercialized as “peixe-branco” (white fish), a designation that is not recognized by the Brazilian regulatory agencies. Both DNA markers (COI and 16S rRNA) were highly efficient in identifying the species from all samples, providing the first list of exploited species for Japanese cuisine along the coastal Amazon. Besides revealing issues in the commercialization of Japanese food items, we recorded a largely overlooked diversity of traded species. These data represent a potential risk to public health and to the environmental conservation such as the presence of exotic species and the exploitation of threatened species that should be considered to support effective policies for the regional regulation of this market.

Profiling Novel, Multifunctional Silane-Phosphonate Consolidants for the Mitigation of Gypsum Stone Deterioration via Concerted Autocondensation/Surface Complexation Processes.

Mineral gypsum (selenite) stones have been used extensively by ancient Cretans in the Minoan Palace of Knossos (Crete, Greece), mostly for building and ornamental purposes. Exposure of mineral gypsum to environmental stresses (temperature fluctuations, rain, air-borne pollutants, soluble salts, etc.) causes solubility-driven degradation, and loss of cohesion of the crystal aggregates, with ensuing aesthetic degradation. In this work, the efficiency of four consolidants for artificial gypsum specimens is presented and evaluated based on drilling resistance measurements [drilling resistance measuring system (DRMS)]. Two of them (commercial names RC-70 and RC-90, RC = Rhodorsil Consolidante) are alkoxysilane-based and they are considered as benchmark consolidants. The other two [3-(trihydroxysilyl)propyl methylphosphonate monosodium salt, TRIMEPHONA, and 3-(trihydroxysilyl)propylamino-diphosphonate, TRIPADIPHOS] are multifunctional consolidants because they possess a self-condensable (after hydrolysis) trihydroxysilyl [-Si(OH)3] moiety and phosphonate groups (one in the former, two in the latter). Consolidants RC-70 and RC-90 exhibit rather low consolidation effectiveness. This is not unexpected, as these are alkoxysilane-based and act simply as "fillers" for the pores of the gypsum. Consolidant TRIMEPHONA demonstrates an enhanced level of consolidation action. This is due to its double functionality, i.e., the presence of an anionic phosphorus-based moiety that anchors onto the gypsum surface, and a condensable silane triol [-Si(OH)3] unit. Consolidant TRIPADIPHOS shows excellent gypsum consolidation features and is much more efficient (per unit concentration) than all other tested consolidants. This is assigned to its better gypsum anchoring ability via surface Ca-complexation. Selected compressive strength studies were performed on gypsum samples treated with the phosphorus-based consolidants, and corroborate the findings from DRMS. To shed further light on possible binding modes of the phosphonate moiety on surface Ca2+ sites in gypsum, two model compounds were synthesized and structurally characterized, Ca-C2D and Ca-C3D (C2D = ethylamino-di(methylenephosphonic acid) and C3D = propylamino-di(methylenephosphonic acid).

Assessment of environmental hazard impacts in building materials (Marble), Gabal El-Galala El-Bahariya, Northeastern Desert, Egypt

Galala limestone is widely used for construction and ornamental purposes and is known throughout the world under many commercial names, including Galala White, Galala Golden, Galala Creama and Galala Classic. Using a HPGe spectrometer, about 20 samples from the marble building industry were radiometrically analyzed and the gamma radiation emitted by the radionuclides 238U, 232Th and 40K was evaluated. The measurements performed showed that the concentrations of these radionuclides were 15 ± 13, 6 ± 4 and 1100 ± 330 Bq kg−1, respectively. It's important to note that all these recorded values do not exceed the internationally reported average levels of 33, 45 and 412 Bq kg−1for each individual element. The annual effective dose (AED) was estimated. The mean value of AED, 0.07 mSv/y, is comparable to the permissible average of 0.07 mSv/y, respectively. The relationship between radionuclides and their radiological hazard characteristics was studied using various multivariate statistical techniques such as Pearson correlation, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The results indicate that the main contributors to the radiological hazard associated with marble are uranium and potassium. As a result, the use of marble in building materials may not pose a significant risk to public health.

Analysis of public records of lobbying practices of the ultra-processed sugary food and drink industries in Chile: a qualitative study

Given the role of commercial determinants on sugar consumption and health, this study aimed to describe lobbying practices of the ultra-processed sugary food and drinks industries in Chile between 2014 and2022. Official meetings between ultra-processed sugary food and drinks industries and related commercial actors and Chilean government officials were obtained from the Chilean Lobby Registry. Relevant commercial names were initially identified based on their market share and expanded iteratively based on information from relevant meetings. Qualitative analysis followed a deductive-inductive approach using the Corporate Political Activity Model to identify and classify objectives, framing and action strategies. From 237 records identified, the Ministries of Health, Social Development, and Economy were the most frequently lobbied. Industry representatives sought to achieve their short- and long-term objectives by targeting a diverse range of authorities, including Ministers and Under-secretaries, using different strategies. Framing strategies focused on presenting sugary food and drinks industries as socially responsible and legitimate policy actors and criticised public health initiatives as 'bad solutions'. Action strategies aimed to influence policymaking and nurture corporate reputations. Extensive lobbying took place by the sugary food and drinks industries between 2014 and 2022, a period when major public health policies were being discussed in Chile. Lobbying strategies varied to meet industry objectives and targeted a diverse range of government institutions including high-ranking officials. Tighter regulations to stop inappropriate industry influence in public health policymaking are urgently required. Agencia Nacional de Investigación y Desarrollo (Chile)-PhD Scholarship. University College London-Open Access fees.

Efficacy of officinal mixture «Fitogastrol» (gastrointestinal) in drip bags for chronic gastritis according to clinical and endoscopic studies

Chronic gastritis is an extremely common disease. According to statistical studies, gastritis affects almost 90 % of the country's population. In the presented study, the task was to evaluate the effectiveness of gastrointestinal herbal mixture in drip bags (commercial name «Fitogastrol»).

Assessing Comparators of the Trademarks before Confusion for Establishing Unfair Competition through the Social Network – Georgian Perspective

The Article aims to assess regulation of unfair competition through the social network in relation to the trademark by relevant Georgian and international legislation in force. In particular, the Article through comparative analyses describes distinctive matters in the practice of the Georgian National Competition Agency with contrast to best international practice, including case law of EU member states. The Article discuss false and inappropriate advertising using communication means regarding registered trademark and use of internet domain in the context of classifying unfair competition. Besides challenging issues mentioned above, the Article distributes comprehensive study on distinguishing “legal name" and "commercial name” of trademarks before confusion when using for advertising purposes. Accordingly, the Article examines rule of necessity of the cumulative presence of three established (visual, phonetic and semantic) comparators for determination of confusion between trademarks through the prism of unfair competion legislation.

A cross-sectional review of contact allergens in popular self-tanning products

Background: In recent years, self-tanners have become a well-liked alternative to sun tanning and tanning bed usage, as strikingly similar results can be achieved without the harmful side effects of ultraviolet exposure. Objective: The aim of this study is to investigate the presence and prevalence of potential allergens in the most popular self-tanning products. Methods: Five major retailers in the United States were evaluated, from which 17 different brands and 44 unique self-tanning products were analyzed. The ingredients in each self-tanning product were compared with 80 and 36 notable contact allergens taken from the North American Contact Dermatitis Group and Food and Drug Administration–approved T.R.U.E (Thin-Layer Rapid Use Epicutaneous Patch Test), respectively. Results: We found that contact allergens are frequently present in self-tanning products; allergens especially common are propylene glycol, linalool, polysorbate, d-limonene, benzyl alcohol, tocopherol (vitamin E), fragrances, and other scented botanicals. On average, each self-tanner we analyzed contained 11.86 allergens. Limitations: The limitation is that commercial names could not be eliminated from the analysis, introducing potential bias. Conclusion: While self-tanning products are a safer alternative to tanning bed use or sunbathing, consumers and clinicians alike must be aware that they may cause an allergic reaction of the skin for some users.

Новый взгляд на проблему заимствований: языковая фрустрация vs маркетинговые стратегии

The article reveals linguocognitive mechanisms as well as social reasons for active functioning of new borrowings in the modern public discourse and in commercial enterprises naming. The material for the analysis is a sample of the most frequent lexis in the micro synchrony that are not yet part of the host language lexicon, and comprises over one hundred and fifty lexical units, selected from the national corpus of the Russian language, public internet discourse, the author's collection of brand names (and names of businesses), radio and television programs. As a result of a comprehensive analysis, two main isomorphic types of borrowing functioning are identified. They are supposed to be motivated by multi-level linguistic, social, and pragmatic factors. Hence, the evidence of linguomental transformations of meaning is linked to the condition of linguistic frustration. This justifies considering it as a state of linguistic personality (at both the first and second levels, according to Yu.N. Karaulov), wherein the constraints of linguistic norms are lifted, and foreign-language word usage is motivated in specific speech act. A tendency of duplicate (native and foreign) naming in explicitly nominative and implicitly subjective-pragmatic functions has been established. It is suggested that the synergy of these functions conveys the speaker's subjective intentions and can be regarded as a marketing strategy of self-positioning in the act of foreign-language use in the nomination process, or as a commercial move, emphasizing the value of the product / service (i.e., commercialization of the nominative unit). Thus, the discourse becomes either status-oriented or conative. The linguistic phenomena under consideration introduce changes into the national concept sphere, as they contain features of a different language world view.

GenX analogs exposure induced greater hepatotoxicity than GenX mainly via activation of PPARα pathway while caused hepatomegaly in the absence of PPARα in female mice

Despite their use as substitutes for perfluorooctanoic acid, the potential toxicities of hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name: GenX) and its analogs (PFDMOHxA, PFDMO2HpA, and PFDMO2OA) remain poorly understood. To assess the hepatotoxicity of these chemicals on females, each chemical was orally administered to female C57BL/6 mice at the dosage of 0.5 mg/kg/d for 28 d. The contribution of peroxisome proliferator-activated receptors (PPARα and γ) and other nuclear receptors involving in these toxic effects of GenX and its analogs were identified by employing two PPAR knockout mice (PPARα−/− and PPARγΔHep) in this study. Results showed that the hepatotoxicity of these chemicals increased in the order of GenX < PFDMOHxA < PFDMO2HpA < PFDMO2OA. The increases of relative liver weight and liver injury markers were significantly much lower in PPARα−/− mice than in PPARα+/+ mice after GenX analog exposure, while no significant differences were observed between PPARγΔHep and its corresponding wildtype groups (PPARγF/F mice), indicating that GenX analog induce hepatotoxicity mainly via PPARα instead of PPARγ. The PPARα-dependent complement pathways were inhibited in PFDMO2HpA and PFDMO2OA exposed PPARα+/+ mice, which might be responsible for the observed liver inflammation. In PPARα−/− mice, hepatomegaly and increased liver lipid content were observed in PFDMO2HpA and PFDMO2OA treated groups. The activated pregnane X receptor (PXR) and constitutive activated receptor (CAR) pathways in the liver of PPARα−/− mice, which were highlighted by bioinformatics analysis, provided a reasonable explanation for hepatomegaly in the absence of PPARα. Our results indicate that GenX analogs could induce more serious hepatotoxicity than GenX whether there is a PPARα receptor or not. These chemicals, especially PFDMO2HpA and PFDMO2OA, may not be appropriate PFOA alternatives.