Cell culture aminoglycosides

Primary renal cell culture has been utilized to study a number of nephrotoxic agents including mercuric chloride (Inamoto et al., 1976), cadmium (Cherian, 1982), lead (McLachlin et al., 1980), cisplatin (Tay et al., 1988), aminoglycoside antibiotics... 

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

Takahashi, N., Mukai, Y., Nakaizumi, H., Sasaki, K. An Evaluation of the cytotoxicity of ophthalmic solutions in cell culture aminoglycosides and dexamethasone sodium phosphate in Concepts Toxicol. 4, Drug-Induced Ocular Side Effects and Ocular Toxicology, Karger, Basel (1987)... 

Sens, M.A., Hennigar, G.R., Hazen-Martin, D.J. and Sens, D.A. (1988). Cultured human proximal tubule cells as a model for aminoglycoside nephrotoxicity. Ann. Clin. Lab. Set 18 204-214. 

Wilhelm JM, Jessop JJ, Pettitt SE, Aminoglycoside antibiotics and eukaryotic protein synthesis stimulation of errors in the translation of natural messengers in extracts of cultured human cells, Biochem, 1978,17(7) 1149-53. 

The usual duration of therapy for peritonitis associated with CAPD is 10 to 14 days, but up to 3 weeks of therapy may be required. Antimicrobial therapy should be continued until dialysate fluid is clear, cultures are negative for 2 to 3 days, and the patient is asymptomatic. When parenteral agents are administered, the initial dose would be the same as that for patients with normal renal function, whereas subsequent doses should be much less or given less frequently for renally excreted agents and should account for possible loss through peritoneal dialysis. Serum concentrations should be performed for aminoglycosides and vancomycin. Some studies have demonstrated that for patients with spontaneous bacterial peritonitis associated with cirrhotic ascites, treatment duration may be as short as 5 days when ascitic fluid polymorphonuclear cell counts are used to guide treatment. 

Gentamicin was found to induce an activation of cultured mesangial cells, as measured by contraction (PCSA) and proliferation. Since gentamicin increases the expression of inducible nitric oxide (iNOS) in these cells [202] and has been shown to elevate intracellular Ca + (via influx, and release from internal stores) [203], it is postulated that nitric oxide-induced Ca2+ elevation might be responsible for the observed effect. These results are in support of a mesangial cell role in the reduction of glomerular filtration rate after aminoglycoside intoxication [204, 205]. 

Reflecting the bacterial ancestry of mitochondria, mitochondrial ribosomes resemble bacterial ribosomes and differ from eukaryotic cytosolic ribosomes in their RNA and protein compositions, their size, and their sensitivity to certain antibiotics (see Figure 4-24). For instance, chloramphenicol blocks protein synthesis by bacterial and mitochondrial ribosomes from most organisms, but cycloheximide does not. This sensitivity of mitochondrial ribosomes to the important aminoglycoside class of antibiotics is the main cause of the toxicity that these antibiotics can cause. Conversely, cytosolic ribosomes are sensitive to cycloheximide and resistant to chloramphenicol. In cultured mammalian cells the only proteins synthesized in the presence of cycloheximide are encoded by mtDNA and produced by mitochondrial ribosomes. I... 

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