Abstract
Gentamicin is a potent antibiotic with a nephrotoxicity drawback which limits its use. D-α-tocopherol polyethylene glycol succinate (α-tocopherol) is widely used as a surfactant and have potent antioxidant properties. This study aimed to assess the protective effect of α-tocopherol on gentamicin-induced nephrotoxicity by loading gentamicin on nanostructured lipid carriers (NLC). In vivo, the product was administered intravenously to three groups of rabbits (control, gentamicin and gentamicin/α-tocopherol NLC) for 10 consecutive days. Blood was collected on days 1, 5 and 10 to assess renal function. A significant difference in all plasma parameters related to kidney function were observed in the gentamicin group compared to the control by day 5 and 10, confirming the nephrotoxicity effect. On the other hand, the same parameter levels of the NLC group were significantly different compared to the gentamicin group, confirming the protective effect on kidney function. Gentamicin also caused significant decreases in plasma levels of glutathione sulfhydryl (GSH) and superoxide dismutase (SOD) activity. However, gentamicin-α-tocopherol NLC significantly elevates both plasma levels of GSH as well as SOD activity. The present work indicates that, loading of gentamicin on NLC by using α-tocopherol, is an innovative strategy to protect against aminoglycoside-induced nephrotoxicity due to its antioxidant activity.
Highlights
Aminoglycoside is one of the potent bactericidal antibiotics that have been used since 1944 againstGram-negative bacteria and synergistically with β-lactam antibiotics against some Gram-positive bacteria [1,2,3]
Despite the numerous advantages associated with this class of antibiotics, such as the post-antibiotic effect, low cost and low rate of microbial resistance, nephrotoxicity remain one major serious side effect of aminoglycosides contributing to their limited use in the current medical practice with an incidence reaching 10–25% [4,5,6,7]
The mechanism by which aminoglycosides cause nephrotoxicity has been explained by multiple potential mechanisms; renal tubular toxicity is the primary mechanism used to describe the nephrotoxic effect of gentamicin [7]
Summary
Aminoglycoside is one of the potent bactericidal antibiotics that have been used since 1944 againstGram-negative bacteria and synergistically with β-lactam antibiotics against some Gram-positive bacteria [1,2,3]. Aminoglycoside is one of the potent bactericidal antibiotics that have been used since 1944 against. Gentamicin is one of the most commonly used aminoglycosides in the clinical setting. The mechanism by which aminoglycosides cause nephrotoxicity has been explained by multiple potential mechanisms; renal tubular toxicity is the primary mechanism used to describe the nephrotoxic effect of gentamicin [7]. Published studies have shown gentamicin stimulates the production of free radicals, such as relative oxygen species (ROS), which induce renal injury via peroxidation of cell membrane lipids, protein denaturation and DNA damage [3,12,13]. Scavenging ROS ameliorates gentamicin nephrotoxicity by zinc-induced metallothionein synthesis [14]
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