Antibacterial Drugs and Their Interference with the Biogenesis of Mitochondria in Animal and Human Cells

Overview

Journal Pharm Weekbl Sci

Specialty Pharmacy

Date 1983 Jun 24

PMID 6348697

Citations 12

Authors

A M Kroon

C Van den Bogert

Affiliations

Soon will be listed here.

Abstract

Mitochondrial RNA and protein synthesis in mammalian cells is sensitive to inhibition by a variety of antibiotics which are used in medical practice. In spite of the intrinsic sensitivity of the synthetic processes to these drugs it appears that inhibition in intact cells and living organisms is not observed in all cases because the cellular membranes may act as barriers which prevent the antibiotics from reaching their intramitochondrial targets. This holds for the rifamycins, the lincomycins and a number of macrolides, but not for chloramphenicol and its analogues. Some of the toxic side-effects of the latter antibiotics can be related to their antimitochondrial action. For the tetracyclines selectivity in permeability exists in the sense that some cell types are permeable and other are not. The hypothesis is developed that the deliberate inhibition of mitochondrial protein synthesis in vivo may lead to cell proliferation arrest and offer a device in combined modality treatments of malignant growths. This hypothesis is supported by the results of two studies with experimental tumour models in rats and by retrospective and prospective clinical data.

Citing Articles

Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.

Thomas C, Wurzer L, Malle E, Ristow M, Madreiter-Sokolowski C Front Aging. 2022; 3:905261.

PMID: 35821802 PMC: 9261327. DOI: 10.3389/fragi.2022.905261.

Mitochondria and Antibiotics: For Good or for Evil?.

Suarez-Rivero J, Pastor-Maldonado C, Povea-Cabello S, Alvarez-Cordoba M, Villalon-Garcia I, Talaveron-Rey M Biomolecules. 2021; 11(7).

PMID: 34356674 PMC: 8301944. DOI: 10.3390/biom11071050.

Selective toxicity of antibacterial agents-still a valid concept or do we miss chances and ignore risks?.

Dalhoff A Infection. 2020; 49(1):29-56.

PMID: 33367978 PMC: 7851017. DOI: 10.1007/s15010-020-01536-y.

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: "Are cell culture data skewed?".

Elliott R, Jiang X PLoS One. 2019; 14(4):e0214586.

PMID: 30934018 PMC: 6443165. DOI: 10.1371/journal.pone.0214586.

Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis.

Wilson R, Kumar P, Parashar V, Vilcheze C, Veyron-Churlet R, Freundlich J Nat Chem Biol. 2013; 9(8):499-506.

PMID: 23770708 PMC: 3720791. DOI: 10.1038/nchembio.1277.

References

Van den Bogert C, Kroon A . Tissue distribution and effects on mitochondrial protein synthesis of tetracyclines after prolonged continuous intravenous administration to rats. Biochem Pharmacol. 1981; 30(12):1706-9. DOI: 10.1016/0006-2952(81)90403-2. View

Van den Bogert C, Kroon A . Fluorometric determination of tetracyclines in small blood and tissue samples. J Pharm Sci. 1981; 70(2):186-9. DOI: 10.1002/jps.2600700218. View

Van den Bogert C, Dontje B, Wybenga J, Kroon A . Arrest of in vivo proliferation of Zajdela tumor cells by inhibition of mitochondrial protein synthesis. Cancer Res. 1981; 41(5):1943-7. View

de Vries H, Arendzen A, Kroon A . The interference of the macrolide antibiotics with mitochondrial protein synthesis. Biochim Biophys Acta. 1973; 331(2):264-75. DOI: 10.1016/0005-2787(73)90439-5. View

de Jong L, Holtrop M, Kroon A . The biogenesis of rat mitochondrial ATPase. Two subunits are synthesized inside the mitochondria. Biochim Biophys Acta. 1980; 608(1):32-8. DOI: 10.1016/0005-2787(80)90130-6. View

Van den Bogert C, Dontje B, Kroon A . Arrest of in vivo growth of a solid Leydig cell tumor by prolonged inhibition of mitochondrial protein synthesis. Cancer Res. 1983; 43(5):2247-51. View

Van den Bogert C, Lont M, Mojet M, Kroon A . Impairment of liver regeneration during inhibition of mitochondrial protein synthesis by oxytetracycline. Biochim Biophys Acta. 1983; 722(3):393-400. DOI: 10.1016/0005-2728(83)90054-3. View

Van den Bogert C, Kroon A . Effects of oxytetracycline on in vivo proliferation and differentiation of erythroid and lymphoid cells in the rat. Clin Exp Immunol. 1982; 50(2):327-35. PMC: 1536698. View

Nijhof W, Kroon A . The interference of chloramphenicol and thiamphenicol with the biogenesis of mitochondria in animal tissues. A possible clue to the toxic action. Postgrad Med J. 1974; 50 Suppl 5:53-9. View

10.

YUNIS A, Manyan D, ARIMURA G . Comparative effect of chloramphenicol and thiamphenicol on DNA and mitochondrial protein synthesis in mammalian cells. J Lab Clin Med. 1973; 81(5):713-8. View

11.

Siegel D . Tetracyclines: new look at old antibiotic. I. Clinical pharmacology, mechanism of action, and untoward effects. N Y State J Med. 1978; 78(6):950-6. View

12.

Cunha B, Comer J, Jonas M . The tetracyclines. Med Clin North Am. 1982; 66(1):293-302. DOI: 10.1016/s0025-7125(16)31461-4. View

13.

Gadaleta M, Greco M, Saccone C . The effect of rifampicin on mitochondrial RNA polymerase from rat liver. FEBS Lett. 1970; 10(1):54-56. DOI: 10.1016/0014-5793(70)80414-8. View

14.

de Jonge H . Toxicity of tetracyclines in rat-small-intestinal epithelium and liver. Biochem Pharmacol. 1973; 22(21):2659-77. DOI: 10.1016/0006-2952(73)90127-5. View