ABSTRACT
This study aimed to determine the adverse effects of oxytetracycline and enrofloxacin application on the fertility of Saanen bucks. For this purpose, twenty-four bucks were divided into three groups. Group I (control group) received only 5 ml of 0.9% NaCl for 7 days, group II was given a single dose of 20 mg/kg oxytetracycline and group III was given at a dose of 2.5 mg/kg per day for 7 days intramuscularly. Serum and semen samples were collected from the bucks at post-treatment 1, 3, 5, 7, and 9 days and examined spermatological parameters (quantity, motility, density, abnormal sperm ratio, and live-dead sperm ratio), serum testosterone levels (with ELISA) and sperm DNA parameters (with Comet assay). The results showed no change in sperm volume, abnormal sperm rate, and dead-live sperm ratio in group II and III following oxytetracycline and enrofloxacin administration. However, a decrease in sperm density, sperm motility, mass activity, and testosterone levels, and an increase in sperm DNA damage were detected. These spermatological parameters (density, motility, mass activity) and testosterone levels were less decreased and sperm DNA damage was less increased in group II than group III. The greater damage in group III may be attributed to the longer duration of enrofloxacin administration compared to oxytetracycline and the effect of enrofloxacin on DNA. The results obtained from this study suggest that usage of oxytetracycline and especially enrofloxacin should be restricted and antibiotics with fewer side effects on sperm should be preferred in Saanen bucks during the reproduction period.
Subject(s)
Oxytetracycline , Sperm Motility , Animals , Enrofloxacin , Fertility , Goats , Male , Oxytetracycline/adverse effects , Semen , Semen Analysis/veterinary , SpermatozoaABSTRACT
Oxytetracycline (OTC) is one of the broad-spectrum antibiotics widely used for the treatment of fish-farm infection. Considering that behavior is directly related to reproduction, individual fitness, and survival, it is important to evaluate the impact of antibiotics on the behavioral repertoire in fish. Zebrafish (Danio rerio) presents a well-described behavioral repertoire to reliably demonstrate complex responses to chemical compound exposure. This work aims to identify the role of OTC in comprehensive behavioral parameters and whole-body cortisol levels in adult zebrafish. Here we report that OTC exposure (10, 20, and 100 mg/L) induces an anxiogenic-like phenotype in the novel tank test. OTC exposure also changes the behavior of social interaction with a shoal of unknown zebrafish - characterized as a stimulus group. Zebrafish exposed to OTC (10 mg/L) remains a longer period in the stimulus zone when compared to the control group. Clonazepam (0.006 mg/L) was able to reverse anxiogenic-like behavior and the changes in social behavior induced by OTC. We also demonstrated that cortisol levels were significantly decreased after exposure to OTC (10, 20, and 100 mg/L), which were not reversed by clonazepam. These findings highlight the growing utility of zebrafish as a model to understand the impact of antibiotics on behavior and their underlying mechanisms.
Subject(s)
Anti-Bacterial Agents/adverse effects , Anxiety/chemically induced , Behavior, Animal/drug effects , Oxytetracycline/adverse effects , Zebrafish , Animals , Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Aquaculture , Clonazepam/therapeutic use , Female , GABA Modulators/therapeutic use , Hydrocortisone/metabolism , MaleABSTRACT
Effects of the dietary therapeutic dose of oxytetracycline (OTC) at 80 mg/kg biomass/day for consecutive 10 days on the behaviour, feed intake, mortality, residue accumulation and depletion, antioxidant capacity and immune-related genes expression in juvenile Nile tilapia Oreochromis niloticus were evaluated. OTC-dosing caused mortalities, reduced feed intake, and biomass reduction at 24.5-28.5 °C. OTC residues recorded on day 10 (161.40 ± 11.10 ng/g) were within the maximum residue limits of the Codex Alimentarius. The withdrawal period was 7 days as per the European Commission's regulation. Traces of residues were present even on day 42 post-OTC-dosing. Dietary OTC reduced the antioxidant capacity of the liver and muscle tissues and down-regulated the expression of tumour necrosis factor-α, interleukin-1ß, and heat shock protein-70 genes in the liver significantly during the dosing period. The data generated on the biosafety of OTC-dosing may offer inputs for the development of management strategies in maintaining fish health and food safety.
Subject(s)
Anti-Bacterial Agents/adverse effects , Cichlids , Oxytetracycline/adverse effects , Animals , Cichlids/genetics , Cichlids/growth & development , Cichlids/immunology , Cichlids/metabolism , Diet/veterinary , Eating/drug effects , Fish Proteins/genetics , Fish Proteins/metabolism , Gene Expression Regulation/drug effects , HSP70 Heat-Shock Proteins/genetics , Interleukin-1beta/genetics , Liver/drug effects , Liver/immunology , Liver/metabolism , Malondialdehyde/metabolism , Muscles/drug effects , Muscles/metabolism , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.
Subject(s)
Anti-Bacterial Agents/adverse effects , Bees/drug effects , Gastrointestinal Microbiome/drug effects , Lactobacillus/drug effects , Oxytetracycline/adverse effects , Animals , Bees/immunology , Bees/microbiology , Digestive System/immunology , Digestive System/microbiology , Gastrointestinal Microbiome/immunology , Lactobacillus/metabolism , Lactobacillus/physiology , Larva/microbiologyABSTRACT
Hormesis is a concentration-response phenomenon characterized by low-concentration stimulation and high-concentration inhibition, which typically has a nonmonotonic J-shaped concentration-response curve (J-CRC). The concentration addition (CA) model is the gold standard for studying mixture toxicity. However, the CA model had the predictive blind zone (PBZ) for mixture J-CRC. To solve the PBZ problem, we proposed a segmented concentration addition (SCA) method to predict mixture J-CRC, which was achieved through fitting the left and right segments of component J-CRC and performing CA prediction subsequently. We selected two model compounds including chlortetracycline hydrochloride (CTCC) and oxytetracycline hydrochloride (OTCC), both of which presented J-CRC to Aliivibrio fischeri (AVF). The seven binary mixtures (M1-M7) of CTCC and OTCC were designed according to their molar ratios of 12:1, 10:3, 8:5, 1:1, 5:8, 3:10, and 1:12 referring to the direct equipartition ray design. These seven mixtures all presented J-CRC to AVF. Based on the SCA method, we obtained mixture maximum stimulatory effect concentration (ECm) and maximum stimulatory effect (Em) predicted by SCA, both of which were not available for the CA model. The toxicity interactions of these mixtures were systematically evaluated by using a comprehensive approach, including the co-toxicity coefficient integrated with confidence interval method (CTCICI), CRC, and isobole analysis. The results showed that the interaction types were additive and antagonistic action, without synergistic action. In addition, we proposed the cross point (CP) hypothesis for toxic interactive mixtures presenting J-CRC, that there was generally a CP between mixture observed J-CRC and CA predicted J-CRC; the relative positions of observed and predicted CRCs on either side of the CP would exchange, but the toxic interaction type of mixtures remained unchanged. The CP hypothesis needs to be verified by more mixtures, especially those with synergism. In conclusion, the SCA method is expected to have important theoretical and practical significance for mixture hormesis.
Subject(s)
Aliivibrio fischeri/drug effects , Chlortetracycline/pharmacology , Drug Compounding/methods , Oxytetracycline/pharmacology , Chlortetracycline/adverse effects , Drug Combinations , Hormesis , Microbial Viability/drug effects , Models, Chemical , Oxytetracycline/adverse effects , Toxicity TestsABSTRACT
The development of three generic multi-compartment physiologically based kinetic (PBK) models is described for farm animal species, i.e. cattle, sheep, and swine. The PBK models allow one to quantitatively link external dose and internal dose for risk assessment of chemicals relevant to food and feed safety. Model performance is illustrated by predicting tissue concentrations of melamine and oxytetracycline and validated through comparison with measured data. Overall, model predictions were reliable with 71% of predictions within a 3-fold of the measured data for all three species and only 6% of predictions were outside a 10-fold of the measured data. Predictions within a 3-fold change were best for cattle, followed by sheep, and swine (82%, 76%, and 63%). Global sensitivity analysis was performed to identify the most sensitive parameters in the PBK model. The sensitivity analysis showed that body weight and cardiac output were the most sensitive parameters. Since interspecies differences in metabolism impact on the fate of a wide range of chemicals, a key step forward is the introduction of species-specific information on transporters and metabolism including expression and activities.
Subject(s)
Animal Feed , Livestock/metabolism , Models, Biological , Oxytetracycline/pharmacokinetics , Triazines/pharmacokinetics , Animal Feed/toxicity , Animals , Cattle , Oxytetracycline/administration & dosage , Oxytetracycline/adverse effects , Reproducibility of Results , Sheep, Domestic , Species Specificity , Sus scrofa , Tissue Distribution , Triazines/administration & dosage , Triazines/toxicityABSTRACT
Tilapias are cultured globally and are rising in acceptance as the most important freshwater aquaculture species. Monitoring of serum biomarkers is a promising tool in aquaculture to screen the health status as they are virtuous indicators of extreme stress and organ dysfunction in fish. The present study examined the serum biomarkers of oxytetracycline (OTC)-dosed Nile tilapia Oreochromis niloticus at 0, 80 and 800â¯mg/kg biomass/day, i.e., 0X, 1X, and 10X the approved dose (Xâ¯=â¯80â¯mg OTC/kg biomass/day) for 10 consecutive days. The fish biomass and levels of serum glucose, aspartate aminotransferase, alanine aminotransferase, creatinine and C-reactive protein (CRP) were determined at scheduled intervals. A significant dose-dependent reduction in fish biomass during the OTC-dosing (5.84%) and post-OTC dosing (8.16%) periods was observed. All the serum biomarkers of Nile tilapia increased significantly on day 10 OTC-dosing. Though their levels reduced significantly, normalcy was not achieved even after 42 days of cessation of OTC-dosing, except CRP. The CRP reached the normal level on day 25 post-OTC dosing in the 1X group. The results, thus, demonstrated that the oral OTC-dosing influences the physiological state of apparently healthy Nile tilapia in a dose-dependent manner. These changes were, however, reversible upon discontinuation of OTC-dosing. The set of data observed on growth reduction and elevated serum biomarker levels even after 42 days of cessation of OTC-dosing, thus, raises questions on the utility of oral OTC-dosing.
Subject(s)
Animal Feed , Anti-Bacterial Agents/adverse effects , Aquaculture/methods , Cichlids/physiology , Diet , Oxytetracycline/adverse effects , Stress, Physiological/drug effects , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Biomarkers/blood , Biomass , Blood Glucose/metabolism , C-Reactive Protein/metabolism , Cichlids/blood , Cichlids/growth & development , Creatine/blood , Humans , India , Seafood , TilapiaABSTRACT
Methanotrophs are of great significance for the abatement of methane emission from anoxic environments. Antibiotics are ubiquitous in the environment and can affect microbial activity and community density and composition. However, information about the effect of antibiotics on methanotrophs is still lacking. The current study explored the influences of sulfonamides and tetracyclines on methane oxidation potential (MOP) and methanotrophic density and community structure in freshwater sediment microcosms. The addition of both sulfanilamide (SA) and oxytetracycline (OTC) could increase MOP and particulate methane monooxygenase subunit A (pmoA) gene density but decrease the number of pmoA transcripts. Both SA and OTC could also have impacts on sediment methanotrophic community structure. The antibiotic effects on MOP and methanotrophs were found to depend on the dosage and type of antibiotics. This work could provide some new insights towards the links between methane oxidation and antibiotics.
Subject(s)
Geologic Sediments/microbiology , Methane/metabolism , Oxytetracycline/adverse effects , Sulfanilamide/adverse effects , Water Pollutants, Chemical/adverse effects , Anti-Bacterial Agents/analysis , Bacterial Proteins/analysis , China , Geologic Sediments/chemistry , Lakes/chemistry , Lakes/microbiology , Oxidation-ReductionABSTRACT
The intensive use of antimicrobials in the veal industry is heavily criticized, but drivers for antimicrobial usage (AMU) are still poorly understood. The industry fears that a drastic reduction in AMU would increase mortality, creating an unacceptable welfare issue. The objectives of the present study were to identify risk factors for AMU and to explore the relationship between AMU and mortality. A retrospective cohort study was performed on the antimicrobial registration data from the largest Belgian veterinary veal practice. The data set contained 295 production cycles from 78 farms, representing 146,014 calves and 8 veal companies (also called integrations). The average AMU was 32.3 defined daily dose animal per year (standard deviation: 11.04), of which 76.2% was administered orally and 23.8% parentally. The AMU remained stable between 2014 and 2016 with only a slight, but significant increase in total AMU between 2015 (31.0 defined daily dose animal per year, standard deviation: 10.5) and 2016 (35.1, 10.8). Use of almost all antimicrobial classes decreased over 2014 to 2016; however, use of long-acting macrolides, doxycycline, and aminosides increased significantly. Analysis identified breed (higher use in beef calves compared with dairy and crossbreeds), month of arrival (lower use when arrived in April or May compared with winter months), and veal company as risk factors. The veal company not only significantly affected total AMU, but also affected the majority of the antimicrobial classes. Additionally, breed differences were present for oxytetracycline, colistin, and classic macrolides, and a month effect was present for doxycycline only. These data illustrate that this veterinary practice realized a reduction of 46% in total AMU and of 96% in critically important antibiotics (fluoroquinolones, cephalosporins of the third and fourth generation) compared with the Belgian benchmark from 2007 to 2009. Replacement of critically important drugs by an increased use of long-acting macrolides is worrisome. Mortality risk was very low compared with benchmarks referenced internationally and did not increase with decreasing AMU. Use of trimethoprim-sulfonamides was a risk factor, whereas use of oxytetracycline was a protective factor for mortality. The absence of a relationship with mortality at the current levels of AMU suggests that a further rational reduction is possible. Attention should be paid to consider different AMU benchmarks for different breeds and to include the veal company as a target for antibiotic awareness campaigns.
Subject(s)
Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Cattle Diseases/mortality , Cattle Diseases/prevention & control , Animals , Belgium , Cattle , Cephalosporins/administration & dosage , Cephalosporins/adverse effects , Cohort Studies , Colistin/administration & dosage , Colistin/adverse effects , Doxycycline/administration & dosage , Doxycycline/adverse effects , Farms , Fluoroquinolones/administration & dosage , Fluoroquinolones/adverse effects , Hybridization, Genetic , Macrolides/administration & dosage , Macrolides/adverse effects , Male , Oxytetracycline/administration & dosage , Oxytetracycline/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Honey bees are associated with gut microorganisms essential for their nutrition and health. The composition of the microbial community can be used as a biological health indicator and is characterized using biomarker fatty acids. Commonly, gut microorganisms are exposed to pathogens and to an array of chemical and biological pest control methods. RESULTS: We found a strong negative effect on microbial gut community composition when exposed to the bee pest control chemicals oxytetracycline, oxalic acid and imidacloprid, and when inoculated with the bee pest Nosema spp. and the potential bee pest biocontrol agent Lactobacillus plantarum. Results from the in vitro test with bee pest chemicals showed a differential response of Lactobacillus spp. At the community level, some taxonomic groups were more affected depending on treatment, but sharp changes in the microbial structure were caused by compounds generally considered as bee safe. CONCLUSION: Our results show that pests such as Nosema spp. and pest control methods alter the composition of bee gut microorganisms, which may have severe consequences for pathogen defense, physiology and general honey bee health. In addition, L. plantarum has potential as a biocontrol agent against Nosema spp. © 2018 Society of Chemical Industry.
Subject(s)
Bees/microbiology , Gastrointestinal Microbiome/drug effects , Nosema , Pest Control, Biological/methods , Animals , Bees/drug effects , Insecticides/adverse effects , Lactobacillus plantarum/drug effects , Microsporidiosis/drug therapy , Neonicotinoids/adverse effects , Nitro Compounds/adverse effects , Oxalic Acid/adverse effects , Oxytetracycline/adverse effectsABSTRACT
To investigate the adverse effect of two widely used pharmaceuticals, paracetamol (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus rotundiformis (B. rotundiformis), the animals were exposed to various environmentally-relevant concentrations. Up to date, acetaminophen and oxytetracycline have been considered as toxic, if used above threshold concentration, i.e. overdosed. However, this study demonstrated these two pharmaceuticals even at low concentration (i.e., µg/L scale) elicited oxidative stress through the generation of reactive oxygen species (ROS) along with the increased glutathione S-transferase activity, despite no-observed effect in in-vivo population growth. To validate the adverse effects of the two pharmaceuticals at relatively low concentrations, mRNA expression analysis was performed of the entire set of genes encoding 26 cytochrome P450s (CYPs) of phase I and 19 glutathione S-transferases (GSTs) of phase II of the rotifer B. rotundiformis. The mRNA expression analysis suggested specific genes CYP3045A2 and GSTσ1, GSTσ4, and GSTω1 take part in detoxification of APAP and OTC, resulting in no significant changes in the population growth and undetermined no observed effect concentration (NOEC) in the marine rotifer B. rotundiformis.
Subject(s)
Acetaminophen/adverse effects , Life Cycle Stages/drug effects , Oxidative Stress/drug effects , Oxytetracycline/adverse effects , Rotifera/growth & development , Rotifera/immunology , Acetaminophen/chemistry , Animals , Antioxidants/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Oxytetracycline/chemistry , Reactive Oxygen Species/metabolism , Rotifera/drug effects , Rotifera/enzymology , Toxicity Tests, Acute , Water Pollutants, Chemical/toxicityABSTRACT
The use of antibiotics for anti-infection and growth promotion has caused the overuse of antibiotics in aquaculture. However, the benefit or risk of the long-term use of antibiotics on fish growth or health has not been fully addressed. In the present study, zebrafish were fed with sulfamethoxazole (SMX) or oxytetracycline (OTC) at the therapeutic concentrations (100 and 80 mg/kg body weight per day, respectively) for 6 weeks to mimic the long-term use of antibiotics. The digestive enzyme activities were higher in both antibiotic treatments, and higher oxygen consumption rate was found in OTC treated group. As a result, SMX increased the weight gain of zebrafish, and OTC treatment did not show significant prompting effect on growth. The mortality was higher in SMX or OTC treated group on 2nd-4th day after exposure to Aeromonas hydrophila. Lower alkaline phosphatase (AKP) and acid phosphatase (ACP) activities were found in OTC treated group, while higher malondialdehyde (MDA) content was found in the intestine of both SMX and OTC treated zebrafish. Furthermore, feeding OTC decreased the intestinal microbial richness. This study revealed that long-term use of legal aquaculture concentrations of antibiotics caused systemic adverse effects on fish gut health; stringent policy for use of antibiotics in fish is urgent.
Subject(s)
Anti-Bacterial Agents/adverse effects , Gastrointestinal Microbiome/drug effects , Oxytetracycline/adverse effects , Sulfamethoxazole/adverse effects , Zebrafish/growth & development , Animals , Time Factors , Zebrafish/physiologyABSTRACT
Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 µg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1ß gene expression and IL-1ß protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases.
Subject(s)
Anti-Bacterial Agents/adverse effects , Mucus/metabolism , Oxytetracycline/adverse effects , Anti-Bacterial Agents/pharmacology , Cell Line , Down-Regulation/drug effects , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Inflammation , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Mucin 5AC/genetics , Mucin 5AC/metabolism , NF-kappa B/metabolism , Oxytetracycline/pharmacology , Respiratory System/cytology , Signal Transduction/drug effectsABSTRACT
Interactive effect of oxytetracyline (OTC) and lead on soil enzymatic activity and population of microbes was studied in the paper. The results showed effect of pollutants on bacteria, actinomycetes and enzymatic activity increased in the order: (OTC+Pb)>Pb>OTC, (OTC+Pb)>Pb>OTC and (OTC+Pb)>OTC>Pb, respectively. However, impact of pollutants on fungi decreased in the order: (OTC+Pb)Subject(s)
Actinobacteria/drug effects
, Alkaline Phosphatase/metabolism
, Bacteria/drug effects
, Bacterial Proteins/metabolism
, Fungal Proteins/metabolism
, Lead/adverse effects
, Oxytetracycline/adverse effects
, Soil Microbiology
, Soil Pollutants/adverse effects
, Sucrase/metabolism
, Actinobacteria/enzymology
, Actinobacteria/growth & development
, Bacteria/enzymology
, Bacteria/growth & development
, Biomass
, Photoelectron Spectroscopy
ABSTRACT
Contamination of feeds with mycotoxins is a worldwide problem and mycotoxin-detoxifying agents are used to decrease their negative effect. The European Food Safety Authority recently stated guidelines and end-points for the efficacy testing of detoxifiers. Our study revealed that plasma concentrations of deoxynivalenol and deepoxy-deoxynivalenol were too low to assess efficacy of 2 commercially available mycotoxin-detoxifying agents against deoxynivalenol after 3 wk of continuous feeding of this mycotoxin at concentrations of 2.44±0.70 mg/kg of feed and 7.54±2.20 mg/kg of feed in broilers. This correlates with the poor absorption of deoxynivalenol in poultry. A safety study with 2 commercially available detoxifying agents and veterinary drugs showed innovative results with regard to the pharmacokinetics of 2 antibiotics after oral dosing in the drinking water. The plasma and kidney tissue concentrations of oxytetracycline were significantly higher in broilers receiving a biotransforming agent in the feed compared with control birds. For amoxicillin, the plasma concentrations were significantly higher for broilers receiving an adsorbing agent in comparison to birds receiving the biotransforming agent, but not to the control group. Mycotoxin-detoxifying agents can thus interact with the oral bioavailability of antibiotics depending on the antibiotic and detoxifying agent, with possible adverse effects on the health of animals and humans.
Subject(s)
Amoxicillin/therapeutic use , Chickens , Oxytetracycline/therapeutic use , Poultry Diseases/chemically induced , Trichothecenes/antagonists & inhibitors , Amoxicillin/adverse effects , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Bile/chemistry , Body Weight/drug effects , Eating/drug effects , Europe , Female , Male , Oxytetracycline/adverse effects , Poultry Diseases/prevention & control , Trichothecenes/blood , Trichothecenes/metabolismABSTRACT
BACKGROUND: The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. METHODOLOGY: We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)(i114) transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1ß, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. CONCLUSIONS: Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line.
Subject(s)
Anti-Bacterial Agents/adverse effects , Biomarkers , Fish Diseases/immunology , Oxytetracycline/adverse effects , Regeneration/drug effects , Zebrafish/immunology , Animals , Animals, Genetically Modified , Anti-Bacterial Agents/pharmacology , Fish Diseases/chemically induced , Fish Diseases/genetics , Inflammation/chemically induced , Inflammation/immunology , Inflammation/veterinary , Oxytetracycline/pharmacology , Regeneration/immunology , Zebrafish/geneticsABSTRACT
Sinonasal myospherulosis is a foreign body reaction to lipid material used on nasal packing at the conclusion of paranasal sinus surgery. Rare cases have been sporadically reported. We report a case found in a 79-year-old female 8 months after functional endoscopic sinus surgery during which sinus cavities had been packed with gauze coated with Terra-Cortril (a paraffin-based tetracycline/steroid ointment). The preoperative diagnosis was suggested during CT of the paranasal sinuses by the presence of macroscopic paraffin retention cysts having a characteristic fat density. To our knowledge, our case represents the first report of sinonasal myospherulosis suggested by CT.
Subject(s)
Foreign-Body Reaction/etiology , Ointment Bases/adverse effects , Paraffin/adverse effects , Paranasal Sinus Diseases/etiology , Paranasal Sinuses/diagnostic imaging , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/chemistry , Cysts/diagnostic imaging , Cysts/etiology , Drug Combinations , Endoscopy , Female , Foreign-Body Reaction/diagnostic imaging , Humans , Hydrocortisone/adverse effects , Hydrocortisone/chemistry , Middle Aged , Ointments/adverse effects , Ointments/chemistry , Oxytetracycline/adverse effects , Oxytetracycline/chemistry , Paranasal Sinus Diseases/diagnostic imaging , Sinusitis/surgery , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Chemical pleurodesis is widely recommended in the treatment of refractory pleural effusion or pulmonary air leak of different etiologies. Although several agents have been used, many questions have remained unanswered about their toxicity. Talc is the most commonly used agent for the treatment, with rare, serious complications reported. Oxytetracycline pleurodesis in clinical practice has been described in a few studies, but literature reveals no experimental studies using this agent. We performed a prospective, randomized, observer-blinded, controlled study to evaluate the changes in lung histology and systemic response to pleurodesis with oxytetracycline and talc in acute and subacute phases in a rat model. METHODS: Forty-two male albino Wistar rats were divided into three groups and 3 subgroups with 7 animals in each. Group 1 was given oxytetracycline, 35 mg/kg; Group 2 was given talc slurry, 60 mg/kg in 0.5 mL saline solution, and Group 3 was given only 0.5 mL saline intrapleurally. In subgroups "a" the nimls were sacrificed at the postoperative 72nd hour and, in subgroups "b", on the postoperative day 7. The surfaces were graded by microscopic examination. RESULTS: Oxytetracycline produced alveolar collapse, hemorrhage, edema, inflammation at the postoperative 72nd hour and hemorrhage on the postoperative day 7, while talc produced significant edema, inflammation, proliferation, fibrosis at the postoperative 72nd hour and hemorrhage, edema, inflammation, proliferation, and fibrosis on the postoperative day 7 (p < 0.0042). Talc produced significant edema compared to oxytetracycline on the postoperative day 7. On contralateral side, oxytetracycline and talc produced significant hemorrhage on the postoperative day 7 (p < 0.0042). CONCLUSIONS: Both agents were shown to produce pulmonary lesions. In acute phase, the pulmonary side effects of oxytetracycline were more pronounced, whereas the side effects of talc were prolonged to subacute phase. We propose that the occasional side effects in humans may be related to these changes as were observed in our rat model, and like talc, oxytetracycline must be used cautiously in patients with limited respiratory function.
Subject(s)
Anti-Bacterial Agents/adverse effects , Antiperspirants/adverse effects , Lung/drug effects , Oxytetracycline/adverse effects , Pleurodesis/adverse effects , Talc/adverse effects , Animals , Anti-Bacterial Agents/administration & dosage , Lung/pathology , Male , Oxytetracycline/administration & dosage , Rats , Rats, Wistar , Talc/administration & dosageABSTRACT
OBJECTIVES: Previous studies have shown an association between isotretinoin and inflammatory bowel disease (IBD). The majority of patients prescribed isotretinoin for their acne are previously on an extended course of antibiotics. Therefore, it is important to consider antibiotic use as a confounding variable for the development of IBD. METHODS: We performed a retrospective cohort study using The Health Improvement Network database of the United Kingdom. We identified 94,487 individuals with acne who were followed up by a general practitioner for 406,294 person-years. RESULTS: >A prescription for minocycline was received by 24,085 individuals, for tetracycline/oxytetracycline by 38,603 individuals, and doxycycline by 15,032 individuals. IBD was noted in 41 individuals exposed to minocycline, 79 individuals exposed to tetracycline/oxytetracycline, 32 individuals exposed to doxycycline, and 55 (0.11%) individuals not exposed to any of these antibiotics. The hazard ratio (HR) for developing IBD for any exposure to a tetracycline antibiotic was 1.39 (1.02, 1.90). HRs for individual antibiotics were 1.19 (0.79, 1.79) for minocycline, 1.43 (1.02, 2.02) for tetracycline/oxytetracycline, and 1.63 (1.05, 2.52) for doxycycline. For ulcerative colitis, the associations (HR) were 1.10 (0.76, 1.82) for minocycline, 1.27 (0.78, 2.07) for tetracycline/oxytetracycline, and 1.06 (0.53, 2.13) for doxycycline. For Crohn's disease (CD), the associations (HR) were 1.28 (0.72, 2.30) for minocycline, 1.61 (0.995, 2.63) for tetracycline/oxytetracycline, and 2.25 (1.27 4.00) for doxycycline. CONCLUSIONS: Tetracycline class antibiotics, and particularly doxycycline use may be associated with the development of IBD, particularly CD. Potential confounding by previous doxycycline exposure should be considered when assessing whether treatment with other acne medications increases the risk of IBD.
Subject(s)
Acne Vulgaris/drug therapy , Doxycycline/adverse effects , Inflammatory Bowel Diseases/chemically induced , Minocycline/adverse effects , Oxytetracycline/adverse effects , Tetracycline/adverse effects , Chi-Square Distribution , Confounding Factors, Epidemiologic , Dermatologic Agents/adverse effects , Dermatologic Agents/therapeutic use , Doxycycline/therapeutic use , Drug Interactions , Female , Humans , Isotretinoin/adverse effects , Isotretinoin/therapeutic use , Male , Minocycline/therapeutic use , Oxytetracycline/therapeutic use , Proportional Hazards Models , Retrospective Studies , Risk Factors , Statistics, Nonparametric , Tetracycline/therapeutic use , United Kingdom , Young AdultABSTRACT
The growth and mortality of European glass eel Anguilla anguilla 192 days after marking with oxytetracycline and alizarin red S were not significantly different between the two treatments and not different to the unmarked A. anguilla.