No abstract

The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

1 Administration of gentamicin to rats at doses of 20, 40 or 80 mg kg-1 d -1 for 6 days induced nephrotoxicity exhibited by elevated plasma creatinine concentration and a decrease in alkaline phosphatase activity in rat kidney cortex. 2 Gentamicin treatment produced significant elevation in plasma total cholesterol amounting to 70% at the 80 mg kg-1 dose. At this dose, the combined cholesterol fractions of low density and very low density lipoproteins increased by more than two-fold. 3 Gentamicin treatment also caused significant increase in plasma triglyceride concentration, while plasma phospholipid levels showed dose-dependent reductions. 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-1 d-1 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. 5 Plasma phospholipid concentration and the activity of cortical alkaline phosphatase were still significantly lower than control 14 days after cessation of the treatment.

1 This study examines the effect of treating rats with gen tamicin (80 mg kg-1 day-1 intramuscularly (i.m.), for 6 days) alone or with either L-thyroxine or the anti-thyroid drug carbimazole. 2 Gentamicin produced significant increases in serum creatinine and urea concentrations, and significantly reduced the activity of Na+,K+ATPase in renal cortex. The concentration of serum triiodothyronine (T3) was unaffect ed by graded doses (20, 40 and 80 mg kg-1) of the antibiot ic. Histopathologically, gentamicin produced necrosis of proximal tubules in the renal cortical tissues of treated rats. 3 Treatment of rats with either L-thyroxine or carbima zole alone did not significantly affect any of the biochemi cal variables investigated. Carbimazole alone produced only mild tubular necrosis. 4 Treatment of rats with either L-thyroxine (100 μg kg-1 day-1, subcutaneously) for 10 days, and gentamicin (80 mg kg-1, i.m. daily during the last 6 days of treatment signifi cantly reduced the gentamicin-induced increases in serum creatinine and urea concentrations, and increased the activity of cortical N+,K+ATPase to control levels. Histopathologically, the severity of gentamicin-induced tubular necrosis was reduced by L-thyroxine treatment. 5 Carbimazole (12 mg ml-1 in drinking water for 21 days) and gentamicin (80 mg kg-1 i.m.) daily during the last 6 days of treatment, stimulated the increase in serum urea concentration produced by gentamicin, but did not signifi cantly affect the gentamicin-induced changes in serum creatinine or cortical N+,K+ATPase.

The effect of fish oil on gentamicin-induced nephrotoxicity was investigated in rats. Gentamicin (80 mg/kg/day intramuscularly for 6 days) produced the typical pattern of nephrotoxicity as shown by increases in serum creatinine and urea concentrations, and urinary N-acetyl-β-D-glucosaminidase (NAG) activity and proximal renal tubular necrosis. Fish oil (5.0 ml/kg/kday per os for 10 days) partially protected against the nephrotoxicity induced by gentamicin administered during the last 6 days of treatment with fish oil by returning the creatinine and urea concentrations and NAG activity to normal and by ameliorating the histopathological damage. Olive oil (5 mg/kg/day per os for 10 days) was ineffective in protecting rats against gentamicin nephrotoxicity.