Effect of thyroid hormone on gentamicin accumulation in rat proximal tubule lysosomes

T₄ decreases gentamicin nephrotoxicity, but the mechanism is unknown. This study investigated whether T₄ affects renal processing of gentamicin by examining renal cortical gentamicin accumulation and proximal tubular lysosomal volume after 48 h of gentamicin (30 mg/kg twice daily) in rats (GT₄) that had previously received 10 days of T₄ (10 μg/100 g body wt). The pair-fed control group received only gentamicin. A T₄-treated control group and an untreated control group were also pair fed and studied. At the end of the 12-day study the four groups did not differ in food intake, body weight, urine volume, urinary Na⁺ excretion, or urinary K⁺ excretion. Plasma creatinine, inulin clearance, and serum clearance of gentamicin were not different among the groups. Gentamicin accumulation was higher in G vs. GT₄ (2.1 ± 0.1 vs. 1.7 · 0.1 μg/mg protein, P < 0.01). Blinded, computer-assisted electron microscopic analysis of outer cortical proximal tubules showed that lysosomes occupied a significantly smaller fraction of the cell volume in GT₄ (8.1 ± 0.5 vs. 11.6 ± 1.1%, P < 0.02). Thyroxine had no effect on lysosomal volume in non-gentamicin-treated rats. Except for scatter foci of apical vacuolization, proximal tubular cells of both groups were otherwise normal. The results show that chronic T₄ administration decreases renal tubular accumulation of gentamicin, and this effect may in part explain its protective effect against gentamicin nephrotoxicity.