A Comparison between the Nephrotoxic Profile of Gentamicin and Gentamicin Nanoparticles in Mice

Abstract

Aminoglycoside antibiotics are widely used against Gram-negative infections. On the other hand, nephrotoxicity is a deleterious side effect associated with aminoglycoside therapy. Gentamicin is the most nephrotoxic aminoglycoside. Because of serious health complications ensue the nephrotoxicity induced by aminoglycosides, finding new therapeutic strategies against this problem has a great clinical value. This study has attempted to compare the nephrotoxic properties of gentamicin and a new nanosized formulation of this drug in a mice model. Animals were treated with gentamicin (100 mg/kg, i.p. for eight consecutive days) and nanogentamicin (100 mg/kg, i.p. for eight consecutive days). Blood urea nitrogen (BUN), plasma creatinine levels, and histopathological changes of kidney proximal tubule were monitored. It was found that gentamicin caused severe degeneration of kidney proximal tubule cells and an increase in serum creatinine and BUN. No severe injury was observed after nanogentamicin administration. This study proved that nanosized gentamicin is less nephrotoxic.

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“…Blood was collected from the abdominal aorta, transferred to standard tubes (Improvacuter; gel and clot activator‐coated tubes; Guangzhou, China) and centrifuged (3000 g , 10 min, 4°C) to prepare serum. A Mindray BS‐200 auto analyzer and standard kits were employed to assess serum gamma‐glutamyl transpeptidase (γ‐GT), alkaline phosphatase (ALP), Creatinine (Cr), glucose, phosphate, calcium, uric acid and blood urea nitrogen (BUN) . Serum sodium and potassium level were assessed by a flame photometer (Clinical Flame Photometer, Sherwood Scientific, UK).…”

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“…BUN and creatinine are surrogate markers for kidney toxicity while ALT is a surrogate marker for liver toxicity. [37][38][39] The quantified values between the treatment and the control groups for both models were compared by one-way ANOVA with Tukey's multiple comparison post-test at a p-value of 0.05 using Graph Pad prism version 5.00 for Windows to assess organ toxicity. Data are presented as mean parameter value ± S.D of four replicates.…”

“…BUN, and creatinine levels are indicators of kidney function. [38] In cases of renal toxicity, levels of BUN and/or creatinine are elevated. [38] ALT is present in all tissues throughout the entire body, but is particularly concentrated in liver, bile duct, kidney, and bone.…”

“…[38] In cases of renal toxicity, levels of BUN and/or creatinine are elevated. [38] ALT is present in all tissues throughout the entire body, but is particularly concentrated in liver, bile duct, kidney, and bone. [39] Elevated ALT levels are usually indicative of liver toxicity.…”

Non-Transgenic Mouse Models of Kidney Disease

“…Mice treated with gentamicin i.p. have increased levels of BUN and serum creatinine and histological analysis reveals severe vacuolization of renal proximal tubule cells [42]. …”