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]