-
Journal of Biochemical and Molecular... Jan 2021This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty-one female rats were used and...
This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty-one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day-fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.
Topics: Animals; Doxycycline; Embryo, Mammalian; Embryonic Development; Female; Fetus; Organogenesis; Pregnancy; Rats; Rats, Wistar
PubMed: 33016600
DOI: 10.1002/jbt.22613 -
Parasitology Mar 2021There are available data on in vivo studies of monotherapy of zoonotic cutaneous leishmaniasis with some antibacterial drugs (doxycycline) and their comparison with...
There are available data on in vivo studies of monotherapy of zoonotic cutaneous leishmaniasis with some antibacterial drugs (doxycycline) and their comparison with meglumine antimoniate (glucantime). We used golden Syrian hamsters as a laboratory model. Experimental groups were formed, each of which was treated with one of the tested drugs. Infection of animals was carried out with Leishmania major promastigotes. We selected highly virulent strains of L. major culture isolated from human ulcers or rodents. Meglumine antimoniate monotherapy and doxycycline monotherapy are quite effective and do not differ by the 30th day of their use in such indicators as the average degree of local damage and the average number of Leishmania in the lesions. The main differences were recorded in terms of average body weight gain and average clinical recovery in favour of doxycycline. Leishmania in the lesion on the 60th day were completely absent in treatment with doxycycline. The experiment proved the effectiveness of doxycycline monotherapy: Leishmania in the lesions were absolutely absent by the end of the treatment.
Topics: Animals; Antiprotozoal Agents; Disease Models, Animal; Doxycycline; Leishmaniasis, Cutaneous; Mesocricetus; Zoonoses
PubMed: 33190654
DOI: 10.1017/S0031182020002152 -
Scientific Reports Aug 2023Chlamydiosis remains the leading infectious disease and is one of the key factors responsible for the dramatic reduction of koala populations in South-East Queensland...
Chlamydiosis remains the leading infectious disease and is one of the key factors responsible for the dramatic reduction of koala populations in South-East Queensland (SEQ) and New South Wales (NSW) regions of Australia. Possible infection outcomes include blindness, infertility, painful cystitis, and death if left untreated. Studies have reported the treatment efficacy of chloramphenicol and doxycycline, which are the two most commonly administered treatments in diseased koalas, in clinical settings. However, none have directly compared the treatment efficacy of these antibacterials on koala survival. A retrospective study was essential to identify any relationships between the demographical information, and the animals' responses to the current treatment regimens. Associations were explored between six explanatory (sex; maturity; location; clinical signs, treatment; treatment duration) and two outcome variables (survival; post-treatment PCR). Results showed that female koalas had a statistical trend of lower odds of surviving when compared to males (OR = 0.36, p = 0.05). Koalas treated with chloramphenicol for ≥ 28 days had greater odds of surviving than when treated for < 28 days (OR = 8.8, p = 0.02), and those koalas administered doxycycline had greater odds of testing PCR negative when compared to chloramphenicol treatments (OR = 5.45, p = 0.008). There was no difference between the antibacterial treatments (chloramphenicol, doxycycline, and mixed/other) and the survival of koalas. Female koalas had greater odds of exhibiting UGT signs only (OR = 4.86, p < 0.001), and also greater odds of having both ocular and UGT clinical signs (OR = 5.29, p < 0.001) when compared to males. Of the koalas, 28.5% initially had no clinical signs but were PCR positive for C. pecorum. This study enables further understanding of the complex nature between chlamydial infection and response to antibacterial treatment.
Topics: Animals; Male; Female; Phascolarctidae; Retrospective Studies; Doxycycline; Chlamydia; Chlamydia Infections; Anti-Bacterial Agents; Chloramphenicol
PubMed: 37542093
DOI: 10.1038/s41598-023-39832-w -
Annals of Surgery Jul 2020To investigate the effects of local doxycycline administration on skin scarring.
OBJECTIVE
To investigate the effects of local doxycycline administration on skin scarring.
BACKGROUND
Skin scarring represents a major source of morbidity for surgical patients. Doxycycline, a tetracycline antibiotic with off-target effects on the extracellular matrix, has demonstrated antifibrotic effects in multiple organs. However, doxycycline's potential effects on skin scarring have not been explored in vivo.
METHODS
Female C57BL/6J mice underwent dorsal wounding following an established splinted excisional skin wounding model. Doxycycline was administered by local injection into the wound base following injury. Wounds were harvested upon complete wound closure (postoperative day 15) for histological examination and biomechanical testing of scar tissue.
RESULTS
A one-time dose of 3.90 mM doxycycline (2 mg/mL) within 12 hours of injury was found to significantly reduce scar thickness by 24.8% (P < 0.0001) without compromising tensile strength. The same effect could not be achieved by oral dosing. In doxycycline-treated scar matrices, collagen I content was significantly reduced (P = 0.0317) and fibers were favorably arranged with significantly increased fiber randomness (P = 0.0115). Common culprits of altered wound healing mechanics, including angiogenesis and inflammation, were not impacted by doxycycline treatment. However, engrailed1 profibrotic fibroblasts, responsible for scar extracellular matrix deposition, were significantly reduced with doxycycline treatment (P = 0.0005).
CONCLUSIONS
Due to the substantial improvement in skin scarring and well-established clinical safety profile, locally administered doxycycline represents a promising vulnerary agent. As such, we favor rapid translation to human patients as an antiscarring therapy.
Topics: Animals; Cicatrix; Collagen; Disease Models, Animal; Doxycycline; Female; Injections, Intralesional; Mice; Mice, Inbred C57BL; Tensile Strength; Wound Healing
PubMed: 30585822
DOI: 10.1097/SLA.0000000000003172 -
Journal of Microbiological Methods Mar 2022Herein we described a versatile liquid chromatographic method for detection and quantification of the total levels of two antimicrobials [i.e., streptomycin (STM) and...
Herein we described a versatile liquid chromatographic method for detection and quantification of the total levels of two antimicrobials [i.e., streptomycin (STM) and doxycycline (DOX)], in mice plasma and selected tissues, with the aid of a single quadrupole as a detection method. The method included a few sample preparation steps, including freeze-drying and in situ triphasic solvent-assisted defatting, precipitation, and extraction, allowing easy and fast tissue sample processing and avoiding analyte loss. Using a murine model, we demonstrated that mass spectrometry detects simultaneously and with high specificity two of the most widespread antimicrobials used against Brucellosis. An accurate [recoveries varied from 75.23 (bone marrow) to 101.33% (liver)] and sensitive (LoD in the ng g range) method to assess STM and DOX in murine tissue, including subtherapeutic and therapeutic doses of the antimicrobials, was achieved. This validated method can be successfully used to monitor the depletion of STM and DOX in several mice tissues and plasma during metabolism after administration.
Topics: Animals; Brucella abortus; Brucellosis, Bovine; Cattle; Chromatography, High Pressure Liquid; Doxycycline; Mice; Streptomycin; Tandem Mass Spectrometry
PubMed: 35219705
DOI: 10.1016/j.mimet.2022.106436 -
Drug Development Research Dec 2023Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to...
Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to develop immune-based therapies to treat skin infections. Previously, we have shown pan-caspase inhibition as a potential host-directed immunotherapy against community-acquired methicillin-resistant S aureus (CA-MRSA) and other bacterial skin infections. Here, we evaluated the role of irreversible pan-caspase inhibitor emricasan as a monotherapy and an adjunctive with a standard-of-care antibiotic, doxycycline, as potential host-directed immunotherapies against S. aureus skin infections in vivo. We used the established CA-MRSA strain USA300 on the dorsum of WT C57BL/6J mice and monitored lesion size and bacterial burden noninvasively, and longitudinally over 14 days with in vivo bioluminescence imaging (BLI). Mice in four groups placebo (0.5% carboxymethyl cellulose [CMC] solution), placebo plus doxycycline (100 mg/kg), emricasan (40 mg/kg) plus doxycycline, and emricasan only were treated orally twice daily by oral gavage for 7 days, starting at 4 h after injection of S aureus. When compared with placebo, all three groups, placebo plus doxycycline, emricasan plus doxycycline, and emricasan treated group, exhibited biological effect, with reduction of both the lesion size (*p = .0277, ****p < .0001, ****p < .0001, respectively) and bacterial burden (***p = .003, ****p < .0001, ****p < .0001, respectively). Importantly, the efficacy of emricasan against S. aureus was not due to direct antibacterial activity. Collectively, pan-caspase inhibitor emricasan and emricasan plus doxycycline reduced both the lesion size and bacterial burden in vivo, and emricasan is a potential host-directed immunotherapy against MRSA skin infections in a preclinical mouse model.
Topics: Mice; Animals; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Doxycycline; Staphylococcus aureus; Staphylococcal Skin Infections; Mice, Inbred C57BL
PubMed: 37540034
DOI: 10.1002/ddr.22099 -
Annals of Clinical Microbiology and... Sep 2023Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the treatment options are limited.
OBJECTIVE
Therefore, this meta-analysis aimed to estimate resistance rates of genital Mycoplasmas to tetracyclines (tetracycline, doxycycline, and minocycline).
METHODS
We searched the relevant published studies in PubMed, Scopus, and Embase until 3, March 2022. All statistical analyses were carried out using the statistical package R.
RESULTS
The 26 studies included in the analysis were performed in 15 countries. In the metadata, the proportions of tetracycline, doxycycline, and minocycline resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 14.2% (95% CI 8.2-23.2%), 5% (95% CI 3-8.1%), and 11.9% (95% CI 6.3-21.5%), respectively. According to the meta-regression, the tetracycline and minocycline resistance rate decreased over time. Although, the doxycycline resistance rate increased over time. There was a statistically significant difference in the tetracyclines resistance rates between different continents/countries (P < 0.05).
CONCLUSION
The prevalence rate and antibiotic susceptibility profiles vary geographically. Therefore, rigorous or improved antimicrobial stewardship, contact tracing, and enhanced intensive surveillance systems are necessitated for preventing the emergence and further spreading of tetracyclines resistance in genital Mycoplasmas.
Topics: Humans; Mycoplasma; Tetracycline; Doxycycline; Minocycline; Anti-Bacterial Agents
PubMed: 37697380
DOI: 10.1186/s12941-023-00628-5 -
Brain, Behavior, and Immunity Mar 2024The brain-penetrant tetracycline antibiotics, minocycline and doxycycline, have been proposed as potential candidate drugs for treatment of schizophrenia, based on... (Observational Study)
Observational Study
IMPORTANCE AND OBJECTIVE
The brain-penetrant tetracycline antibiotics, minocycline and doxycycline, have been proposed as potential candidate drugs for treatment of schizophrenia, based on preclinical studies and clinical trials. A potential long-term beneficial effect of these antibiotics for schizophrenia patients has not been investigated. This study was designed to determine if redemption of doxycycline prescription in schizophrenia is associated with decreased incidence of disability pension, a proxy for long-term functioning.
DESIGN
We performed a population-based cohort study with data from schizophrenia patients available through the Danish registers. Survival analysis models with time-varying covariates were constructed to assess incidence rate ratios (IRR) of disability pension after exposure to doxycycline or a non-brain penetrant tetracycline, defined as at least one filled prescription. The analysis was adjusted for age, sex, calendar year, parental psychiatric status and educational level.
RESULTS
We used data from 11,157 individuals with schizophrenia (4,945 female and 6,212 male; average age 22.4 years old, standard deviation (std) 4.50). 718 of these were exposed to brain-penetrant doxycycline, and 1,498 individuals redeemed a prescription of one or more of the non-brain-penetrant tetracyclines. The average years at risk per person in this cohort was 4.9, and 2,901 individuals received disability pension in the follow-up period. There was a significantly lower incidence rate of disability pension in schizophrenia patients who had redeemed doxycycline compared to patients who did not redeem a prescription of any tetracycline antibiotics (Incidence rate ratio (IRR) 0.68; 95 % CI 0.56, 0.83). There was also a significant lower rate of disability pension in schizophrenia patients who redeemed doxycycline compared to individuals who redeemed a prescription of one of the non-brain penetrant tetracycline antibiotics (IRR 0.69 95 % CI 0.55, 0.87).
CONCLUSIONS
In this observational study, doxycycline exposure is associated with a reduced incidence of disability pension. These data support further studies on the potential long term neuroprotective effects of doxycycline and level of functioning in schizophrenia patients.
Topics: Female; Humans; Male; Young Adult; Anti-Bacterial Agents; Cohort Studies; Doxycycline; Minocycline; Schizophrenia; Tetracycline
PubMed: 38169245
DOI: 10.1016/j.bbi.2023.12.036 -
Naunyn-Schmiedeberg's Archives of... Aug 2023Doxycycline (DOX) is a widely used antibiotic that is able to cross the blood-brain barrier. Several studies have shown its neuroprotective effect against...
Doxycycline (DOX) is a widely used antibiotic that is able to cross the blood-brain barrier. Several studies have shown its neuroprotective effect against neurodegeneration and have associated it with antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. We have recently demonstrated that DOX mimics nerve growth factor (NGF) signaling in PC12 cells. However, the involvement of this mechanism in the neuroprotective effect of DOX is unknown. Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration, and precede the neuronal death in neurodegenerative diseases, including Parkinson's disease (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD. The effect of DOX in PC12 cells treated with the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP) was addressed. Doxycycline reduced the inhibition of neuritogenesis induced by MPP, even in cells deprived of NGF. The mechanism involved the upregulation of GAP-43, synapsin I, β-III-tubulin, F-actin, and neurofilament-200, proteins that are associated with axonal and synaptic plasticity. Considering the role of axonal degeneration and synaptic loss at the initial stages of PD, the recent advances in early diagnosis of neurodegeneration, and the advantages of drug repurposing, doxycycline is a promising candidate to treat PD.
Topics: Rats; Animals; Humans; Up-Regulation; Doxycycline; Neuroprotective Agents; Nerve Growth Factor; Proteins; Parkinson Disease; PC12 Cells; Tubulin; 1-Methyl-4-phenylpyridinium
PubMed: 36843128
DOI: 10.1007/s00210-023-02435-3 -
Evidence-based Dentistry Dec 2022Design Randomised controlled clinical trial.Data sources Not applicable.Study aims This split-mouth randomised controlled clinical trial assessed the effects of placing... (Review)
Review
Design Randomised controlled clinical trial.Data sources Not applicable.Study aims This split-mouth randomised controlled clinical trial assessed the effects of placing doxycycline hyclate (Atridox) at the implant-abutment interface on the short-term clinical outcomes of dental implants.Methods The study sample included 20 patients; each patient had two mandibular implants placed, one on either side of the mandible, resulting in a total of 40 implants placed in the study sample. At the time of final prosthesis delivery, doxycycline hyclate (Atridox 10% doxycycline hyclate) was injected at the implant-abutment interface of 20 randomly selected implants on the test side (N = 20) while no intervention was done on the control side (N = 20). The primary outcome measure was changes in pocket probing depth while secondary outcome measures included the incidence of peri-implant mucositis, bleeding on probing, and changes in marginal bone levels on mesial and distal bone aspects of the implant. The outcome measures were assessed at baseline, 3 months, 6 months and 12 months.Results The results showed favourable effects of prophylactic doxycycline application. Marginal bone levels and pocket probing depths after 6 and 12 months on the test side were less compared to the control side and these differences were statistically significant. The test side also showed fewer implants with bleeding on probing and lower risk of peri-implant mucositis after 3, 6 and 12 months.Conclusion Prophylactic placement of doxycycline hyclate may reduce peri-implant bone loss and pocket probing depths, and may also reduce the risk of peri-implant mucositis.
Topics: Humans; Doxycycline; Dental Implants; Mucositis; Peri-Implantitis; Treatment Outcome; Dental Implantation, Endosseous; Randomized Controlled Trials as Topic
PubMed: 36526844
DOI: 10.1038/s41432-022-0839-5