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Quercetin-loaded F127 nanomicelles: Antioxidant activity and protection against renal injury induced by gentamicin in rats.

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Quercetin (Q) is formulated into oil-in-water F127 microemulsions to improve its bioavailability. The size of the Q-loaded microemulsions system was about 8 nm by dynamic light scattering analysis. To compare antioxidant… Click to show full abstract

Quercetin (Q) is formulated into oil-in-water F127 microemulsions to improve its bioavailability. The size of the Q-loaded microemulsions system was about 8 nm by dynamic light scattering analysis. To compare antioxidant activity of bulk solution and microemulsion of Q, free radical scavenging activity was evaluated against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 values were 56.77 and 187.68 μM, respectively. The drug in the bulk form released 16.34 times faster than microemulsion form. Although gentamicin (GM) has potent efficacy against gram-negative bacteria, it induces renal toxicity. Poor solubility and low bioavailability of Q as a bioflavonoid with potent antioxidant activity, limit its therapeutic application. We aimed to compare the effect of free Q and nanoencapsulated (NEQ) against GM-induced renal damage in Wistar rats. Forty-two animals were divided into six groups. Control and GM groups received apo-nanomicelles and GM (100 mg/kg) for 10 days. Two groups received Q (50 mg/kg, i.g.) and NEQ (50 mg/kg, i.g.) respectively for 10 days. Remaining two groups received Q and NEQ (50 mg/kg, i.g.) plus GM (100 mg/kg, i.p.) simultaneously for 10 days. After the experiments, serum and kidneys were used for biochemical, molecular and histological examinations. Immunohistochemical analysis was performed to explore kidney injury molecule-1 (KIM-1) expression as a specific protein biomarker of renal injury. Our findings indicated oxidative stress and altered histological features in renal tissue with deviated serum renal biomarkers in GM-treated rats. Although Q treatment in GM group tried to protect against GM-induced nephrotoxicity, but there were still differences compared to control rats. However, NEQ administration corrected elevations in the levels of urea, creatinine, uric acid and decrements in serum total proteins of GM group. Meanwhile, NEQ restored renal oxidative injury in GM rats through attenuation of lipid peroxidation and enhancement of antioxidant defense systems, glutathione, catalase and superoxide dismutase. NEQ could also normalize GM-induced abnormal renal histology features including fibrosis. Furthermore, the result of immunohistochemistry study confirmed these findings by undetecting KIM-1 expression in NEQ treated GM group, meanwhile showing this renal biomarker in GM and Q treated GM groups. Therefore, NEQ seems to be useful in protecting against renal oxidative stress and kidney damage in a rat model of GM nephrotoxicity which deserve further evaluations.

Keywords: antioxidant activity; renal injury; groups received; injury; activity; quercetin loaded

Journal Title: Life sciences
Year Published: 2021

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