Characterization of gentamicin-induced dysfunctions in vitro: the use of optimized primary cultures of rabbit proximal tubule cells.

Abstract:

:Compared to prior studies which frequently pinpoint the impairment of one parameter or function, this paper reports for the first time an extensive characterization of the toxic effects of gentamicin in a single model of primary cultured rabbit proximal tubule cells developed without insulin and glucose. Biochemical, functional and morphological approaches were used. Cellular response pattern was examined after a 72-h exposure during either the exponential growth phase or the stationary confluency phase of the culture to 0.2, 1, and 2.5 mM gentamicin. The biochemical study after gentamicin exposure showed increased activities for N-acetyl-beta-D-glucosaminidase and alkaline phosphatase, decreased activities for sphingomyelinase, cathepsin B, Na+/K(+)-ATPase, lactate dehydrogenase and NADPH cytochrome C reductase. Functional evaluation revealed decreased protein synthesis and alpha-methylglucose transport after gentamicin exposure. Morphometric study made it possible to show that the density of lysosomes, the cell fractional volume of the lysosomal compartment, and the mean size of the lysosomal profiles are increased in the cells. Intracellular accumulation of gentamicin in proximal tubular cells was dose dependent and reached high levels in cultured cells. In conclusion, this model compared to others in the literature allowed us to demonstrate in vitro a close response pattern to the in vivo situation after gentamicin exposure.

journal_name

Ren Fail

journal_title

Renal failure

authors

Monteil C,Leclere C,Fillastre JP,Morin JP

doi

10.3109/08860229309054962

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

475-83

issue

4

eissn

0886-022X

issn

1525-6049

journal_volume

15

pub_type

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