Gentamicin Cisplatin

Clinically important, potentially hazardous interactions with ACE inhibitors, amikacin, aminoglycosides, aminophylline, anti-diabetics, antihypertensives, cephalosporinss, cisplatin, gentamicin, indomethacin, kanamycin, neomycin, probenecid, salicylates, streptomycin, tobramycin... 

Primary cultures of renal tubular, glomerular mesangial and endothelial cells from various species have been developed, including mouse [114], rat [115,116], rabbit [117] and pig [118]. Although cells in primary culture tend to dedifferentiate, the characteristics of those cells are usually closer to the in vivo situation than are animal cell lines, at least for a limited culture period. Primary cultures have been used successfully to study the short-term in vitro effects of cisplatin, gentamicin, cephalosporins, cysteine conjugates, butyl hydroperoxide, mercuric chloride, and cadmium chloride... 

Another 3D model had been developed with immortalized human renal cortical cells embedded into a mix of Matrigel and rat tail collagen (DesRochers et al., 2013). These cells displayed some features of PTC but performed also functions that are not typical for PTC. For instance, the cells were responsive to antidiuretic hormone, whereas they did not respond to parathyroid hormone. The effects of cisplatin, gentamicin, and doxorubicin were tested by measuring cell viability, LDH release, and increase of KIM-1 and NGAL. In compatison to 2D cultures, the 3D model did not clearly improve the results. Also here positive responses to doxorubicin were observed, and in this case the 3D model was more sensitive than 2D cultures to this usually non-PT-damaging drag. 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

To what extent cell lines from the Immorto-Mouse are appropriate inner ear models and thus are useful for ototoxic studies is a matter of debate. On the positive side, the OC-k3 cell line displayed cisplatin-induced apoptotic cell death that was attenuated by inhibition of mitogen-activated protein kinase kinases [86, 87], HEI-OC1 cells were sensitive to gentamicin, streptomycin, cispla-tin, and acetaminophen/hydrocodon [40, 85], However, the HEI-OC1 cell line received some criticism lately, because of the absence of cell death in response to gentamicin [77, 88], These characteristics suggested that the ototoxin-sensitivity of HEI-OC1 depended on the culturing conditions, or that some cell batches had lost their sensitivity to AG-induced cell death. 

The renal toxicity of cisplatin is potentiated by aminoglycoside antibacterials such as gentamicin and tobramycin. Extra care is required in patients treated with cisplatin requiring these antibacterials. In one retrospective analysis in patients taking cisplatin, hearing loss was not associated with the concurrent use of ototoxic drugs, including tobramycin. 

There is also evidence from a study in children to show that previous treatment with cisplatin is a risk factor for the delayed elimination of aminoglycosides (gentamicin, amikacin, tobramycin). ... 

Cisplatin is nephrotoxic and it would appear that its damaging effects on the kidney are additive with the nephrotoxic effects of the aminoglycoside antibacterials. Both gentamicin and cisplatin may cause ototoxicity. Previous exposure to cisplatin caused a significant decrease in gentamicin clearance in rats. 

Engineer MS, Bodey GP, Newman RA, Ho DH. Effects of cisplatin-induced nephrotoxicity on gentamicin pharmacokinetics in rats. DrugMetab Dispos( 9Zl) 15, 329-34. 

Induction of poly(ADP-ribosyl)ation was reported in the kidney after in vivo application of renal carcinogens such as trichloroethene and dichloroacetylene subsequent to DNA double-strand breaks. Potassium bromate and ferric nitrilotriacetate, whose nephrotoxicity is thought to result from ROS formation, both induced poly(ADP-ribosyl)ation with the concomitant formation of DNA double-strand breaks. Recendy, PARP activation has been associated with both gentamicin and cisplatin-induced nephrotoxicity.Both types of nephrotoxicity involve the generation of ROS and the beneficial effects of different therapeutic approaches aimed at reducing ROS formation have been evaluated. 

Decreased magnesium levels, that is, levels of 1.2 mEq/L (0.64 mmol/L) or less, may be noted in patients with conditions that cause excessive urinary loss of magnesium, including poorly controlled diabetes and alcohol abuse, or in patients using drugs such as loop and thiazide diuretics (e.g., Lasix, Bumex, Edecrin, and hydrochlorothiazide), cisplatin (which is used widely to treat cancer), and the antibiotics gentamicin, amphotericin, and cyclosporine. Hypomagnesemia also can... 

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