MUDr. Dana Maňasková

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Tetracykliny

Popis

  • Broad-spectrum polyketide antibiotics
  • Discovered from the Streptomyces genus of actinobacteria
  • Inhibiting bacterial protein synthesis
  • Tetracycline and doxycycline
  • Chlortetracycline and oxytetracycline
  • Acne, chlamydia infections, and Lyme disease
  • Commonly used antibiotic class in veterinary medicine
    • Relatively cheap
    • Can be applied in the diet of farm animals
      • At therapeutic levels to treat disease
      • At a subtherapeutic dose to improve animal growth rates [2]

Interakce

  • Zvýšená exkrece vitaminu B2 [1]
  • Zhoršení metabolismu vit. C a jeho vyšší vylučování ledivnami [1]
  • Snížení produkce vit. K střevními bakteriemi
  • Zvýšená exkrece zinku a zhoršená absorpce zinku ale i tetracyklinu zinkem
  • Tetracykliny snižiují absorpci Fe, a Fe snižuje abs. tetracyklinů [1]

Doporučení pro pacienta

  • Doplnit vit. B2, C
  • Ohlídat případně INR při užívání warfarinu, probiotika
  • Až po dobrání tetracyklinu doplnit dostatek zinku a železa / užívat s odstupem od požití tetracyklinu

Další účinky tetracyklinů

  • Also used as tool compounds in biomedical research to
    • Control the transcriptional regulator (Tet-On/Tet-Off system)
      • Transactivator (tTA) protein
        • Fusion protein of the tetracycline repressor (TetR) of E. coli
        • Trans-activating domain of VP16 of Herpes Simplex Virus [2]
      • Can be used to express genes placed under the control of a tetracycline-response element (TRE)
    • Inhibit matrix metalloproteases
    • To label bone remodeling [2]
  • Doxycycline binds to tTA protein
    • TTA protein is released from the TRE
      • Shuts down transcription
  • Tet-On system basically operating in the opposite fashion
    • Tetracycline binding to the rTA protein
      • Allows it to interact with the TRE
        • Transcriptional activation to occur [8]
  • Tetracyclines occupy the A-site of the bacterial 30S ribosomal subunit
    • Inhibit bacterial polypeptide synthesis
      • Sterically blocking the recruitment of the aminoacyl-tRNA to the bacterial ribosome [8]
  • Ribosomes are biological machines composed of RNAs and proteins
    • Responsible for protein synthesis [8]
  • Tetracyclines are potent inhibitors of mitochondrial translation in rat heart and liver
  • Tetracyclines reduce cell proliferation in various human cell lines
    • Cause many adverse effects in thymocytes and HepG2 cells
  • Doxycycline disturbed mitochondrial proteostasis
    • Induction of an imbalance between mitochondrial and nuclear protein production
      • Aka the mitonuclear protein imbalance observed in
        • Human embryonic kidney (HEK) [8]
        • HeLa cells
        • In mouse hepatoma Hepa1-6
        • Hypothalamic GT1-7 cell lines [8]
  • In mouse and human cells, the induction of mitonuclear protein imbalance was accompanied by
    • Major changes in mitochondrial function
      • Oxygen consumption rate
    • mitochondrial dynamics
      • Induced fragmented mitochondria [8]
    • Marked repression of ~10% of nuclear genes
  • Doxycycline impaired development and mitochondrial function in the nematode C. elegans and the fruit fly D. melanogaster
  • C57BL/6J mice that drank water containing doxycycline (50 or 500 mg/kg/day) for 14 days
    • Similar mitonuclear imbalance and mitochondrial dysfunction
    • Energy expenditure was reduced in doxycycline-treated mice, compared to the controls receiving amoxicillin [8]
  • In plants, 25 mg/L doxycycline
    • Severely repressed growth of Arabidopsis seedlings
    • Significantly decreased oxygen consumption
    • Reduced mitochondrial translation [8]
  • Lipid peroxidation and reactive oxygen species (ROS)
    • Frequently found in plants exposed to tetracyclines [8]
    • Literatura:
      [1] Výživa ženy v obdobích těhotenství a kojení, Miloslav Hronek a kol.[2] onlinelibrary.wiley.com/doi/10.1002/bies.201500071/full[3][4][5]
O úroveň výše

Poslední aktualizace: 17. 3. 2018 19:33:35
© Dana Maňasková, metabalance.cz
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