TY - JOUR T1 - Poly-L-aspartic acid does but triiodothyronine does not protect against gentamicin-induced cytotoxicity in the porcine kidney cell line LLC-PK1. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 834 LP - 840 VL - 262 IS - 2 AU - T Whittem AU - R G Schnellmann AU - D C Ferguson Y1 - 1992/08/01 UR - http://jpet.aspetjournals.org/content/262/2/834.abstract N2 - This study investigated the protective effect of thyroid hormone and poly-L-aspartic acid (PAA) in an in vitro model of gentamicin nephrotoxicity. LLC-PK1 porcine renal cells were grown in Medium 199 supplemented with either fetal bovine serum or thyroid hormone-depleted fetal bovine serum. After a preincubation with or without 30 nM L-triiodothyronine for 3 days, or 0.1 mM PAA for 1 hr, cells were coincubated with 1 mM gentamicin for an additional 3 days. Determinations were made of the following indicators of cell damage and/or viability: the numbers of detached dead cells, the total lactate dehydrogenase activity and its percentage release and gamma-glutamyl transpeptidase activity. Preincubation with L-triiodothyronine did not protect from gentamicin-induced cell death but did reduce cellular accumulation of gentamicin (3.2 +/- 0.8 micrograms/mg of protein vs. 5.2 +/- 1.8 micrograms/mg of protein in controls; P less than .05). In contrast, preincubation with 0.1 mM PAA decreased gentamicin-induced cell death (gentamicin: 685 +/- 416% of control dead cells and 487 +/- 48% of control lactate dehydrogenase release; PAA + gentamicin: 164 +/- 63% of control dead cells and 257 +/- 85% of control lactate dehydrogenase release; P less than .05) but failed to attenuate inhibition by gentamicin of gamma-glutamyl transpeptidase activity (gentamicin: 69 +/- 7% of control; PAA+gentamicin: 76 +/- 3% of control) and failed to alter cellular gentamicin levels. Protection against gentamicin nephrotoxicity by L-triiodothyronine was not demonstrated in LLC-PK1 cells, indicating that its protective effect in vivo is likely due to a systemic effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS) ER -