Abstract
The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of Sambucus nigra L. elderflower (SN) to inhibit lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL−1), epicatechin (9.0 ± 1.1 µg mL−1), and ferulic (1.5 ± 0.3 µg mL−1) and caffeic acid (3.6 ± 0.1 µg mL−1). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg−1 bw day−1 GM), GM+SN group (100 mg kg−1 bw day−1 GM and 1 mL SN extract day−1), and SN group (1 mL SN extract day−1). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity—superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)—were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group (p < 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group (p = 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group (p > 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.
Highlights
Gentamicin (GM) is an aminoglycoside antibiotic with high efficacy in treating infections caused by Gram-negative bacteria, but with limited use due to its ototoxic and nephrotoxic effects
RNS are represented by nitric oxide (NO) and peroxy-nitrite (ONOO− ), the latter being formed by the reaction of NO with O2 − [43]
Elderflower extract rich in rutin, caffeic acid acid (CA), and ferulic acid (FA) significantly reduced GM-induced lipid peroxidation, quantified by MDA levels, in the renal tissue
Summary
Gentamicin (GM) is an aminoglycoside antibiotic with high efficacy in treating infections caused by Gram-negative bacteria, but with limited use due to its ototoxic and nephrotoxic effects. National Institute of Health and Care Excellence (NIHCE) guidelines recommend the use of GM (in combination with penicillin) as a first-line therapy in neonates with suspected early-onset sepsis [1]. The occurrence of carbapenemase-producing and/or colistin-resistant Enterobacteriaceaes requires the use of antibiotic combinations that include GM, a drug that was proven effective on these bacteria [2]. These aspects create the premise for increasing GM use and require solutions to counteract its ototoxic and nephrotoxic effects. GM induces nephrotoxicity by concentrating in the proximal renal tubules, in the endosomal and lysosomal vacuoles [3], and in the Golgi complex [4], causing oxidative stress (OS), inflammatory and vascular responses, and acute tubular necrosis.
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