Plasma Lipid Profile in Rats with Gentamicin-Induced Nephrotoxicity

Abstract

<jats:p> 1 Administration of gentamicin to rats at doses of 20, 40 or 80 mg kg<jats:sup>-1</jats:sup> d <jats:sup>-1</jats:sup> for 6 days induced nephrotoxicity exhibited by elevated plasma creatinine concentration and a decrease in alkaline phosphatase activity in rat kidney cortex. </jats:p><jats:p> 2 Gentamicin treatment produced significant elevation in plasma total cholesterol amounting to 70% at the 80 mg kg<jats:sup>-1</jats:sup> dose. At this dose, the combined cholesterol fractions of low density and very low density lipoproteins increased by more than two-fold. </jats:p><jats:p> 3 Gentamicin treatment also caused significant increase in plasma triglyceride concentration, while plasma phospholipid levels showed dose-dependent reductions. </jats:p><jats:p> 4 In another experiment recovery of the aforementioned parameters was assessed 7 and 14 days after the withdrawal of gentamicin, administered at a dose of 40 mg kg<jats:sup>-1</jats:sup> d<jats:sup>-1</jats:sup> for 6 days. After 7 days from drug discontinuation, both plasma creatinine and total cholesterol concentrations returned to the control levels, while triglyceride concentration was still significantly higher than control 14 days after stoppage of treatment. </jats:p><jats:p> 5 Plasma phospholipid concentration and the activity of cortical alkaline phosphatase were still significantly lower than control 14 days after cessation of the treatment. </jats:p>

Changes in the serum, liver, and renal cortical lipids and electrolytesin rabbits with cisplatin-induced nephrotoxicity

“…On the other hand, several studies have demonstrated that cisplatin and gentamicin but not amikacin can induce secondary dyslipidemia in the rat (14)(15)(16). In the present study we observed similar hypercholesterolemia and hypertriglyceridemia in the cisplatin-treated rabbits.…”

Effect of Fish Oil Treatment on Gentamicin Nephrotoxicity in Rats

“…The antibiotic is known to cause a number of morphological, metabolic and functional alterations [reviewed in 8]. We have recently reported that gentamicin, at the same dose used here, significantly increased plasma triglycerides and decreased plasma phospholipid concentrations [10], Fish oil, on the other hand, is known to be a major source of co-3 fatty acids and alters membrane phos pholipid fatty acid composition and eicosanoid production [11,12]. The protective ef fect is unlikely due to administration of fats per se, as olive oil (which does not contain the said fatty acid) was ineffective in protecting against gentamicin nephrotoxicity.…”

“…Sections were examined by light microscopy by a histopathologist unaware of the treatments. Renal histopathological damage (tubular necrosis) was assessed on a score previously described [10] as follows: 0 = no cell necrosis; 1 = mild, usually single cell necrosis in sparse tubules; 2 = moderate, more than one cell involved in sparse tubules; 3 = marked, tubules exhibiting toral necrosis in almost every power field; 4 = massive total necrosis.…”

Gentamicin nephrotoxicity in animals: current knowledge and future perspectives

“…Gentamicin binds to membrane phospholipids, alters its function and lead to a condition known as phospholipidosis in humans (De Broe et al, 1984[16]) and experimental animals (Nonclercq et al, 1992[58]). Lysosomal phospholipidosis is caused by: disorder in phosphatidylinositol signaling pathway (Ramsammy et al, 1988[65]), reduced turnover of phospholipids and their accumulation in plasma membrane (Laurent et al, 1982[40]), decrease in the available negative charge for proper function of phospholipases (Mingeot-Leclercq et al, 1995[50]), inhibition of calcium dependent phosphodiesterases (Van Rooijen and Agranoff, 1985[90]) and by inhibition of phospholipases A1, A2 and C1 (Abdel-Gayoum et al, 1993[1]). Phospholipidosis is directly related to toxicity of GM (Kaloyanides, 1992[33]).…”