Model of gentamicin-induced nephrotoxicity and its amelioration by calcium and thyroxine.
The exact mechanism of gentamicin-induced acute renal failure is presently unknown; various mechanisms have been proposed but there is no proposed commonality between them. In animals, dietary calcium loading and L-thyroxine administration have been shown to ameliorate toxicity, with again no common process. A mechanism of competitive displacement of calcium and other cations from anionic phospholipids at the plasma and organelle membrane level, resulting in a decrease in Na+ -K+ ATPase, adenylate cyclase, mitochondrial function and ATP production, protein synthesis, solute reabsorption and overall cellular function is proposed. A further proposal is dietary calcium loading and thyroxine (which increases intracellular calcium) reverse gentamicin-induced acute renal failure by increasing the calcium and solute flux, thereby competitively inhibiting the primary lesion: anionic phospholipid binding.
Ernest
S
S
School of Pharmacy, Creighton University, Omaha, NE 68178.
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism; D002118:Calcium / Q000627:therapeutic use*; D005839:Gentamicins / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D013974:Thyroxine / Q000627:therapeutic use*
D005839:Gentamicins; D013974:Thyroxine; D002118:Calcium