A Flavonoid-Rich Extract of Sambucus nigra L. Reduced Lipid Peroxidation in a Rat Experimental Model of Gentamicin Nephrotoxicity

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.

Keywords: antioxidants; elderflower; flavonoids; gentamicin; nephrotoxicity; oxidative stress.

Figure 1

Chemical structures of the main flavonols from Sambucus nigra: rutin (1); isoquercitrin (2); astragaline (3) and antocyanins: cyanidin-3-sambubioside (4); cyanidin-3-glucoside (5) (Created with BioRender.com) [16].

Figure 2

HPLC-UV chromatograms of standards mixture of studied phenolic compounds and analyzed SN ethanolic extract.

Figure 3

Malondialdehyde (MDA) level in the investigated groups (* p < 0.05, **** p < 0.0001). GM—gentamicin group, GM+SN—gentamicin and Sambucus nigra group, SN—Sambucus nigra group, Control—control group (no treatment).

Figure 4

Superoxide dismutase (SOD) level in the investigated groups (** p < 0.01, **** p < 0.0001). GM—gentamicin group, GM+SN—gentamicin and Sambucus nigra group, SN—Sambucus nigra group, Control—control group (no treatment).

Figure 5

Catalase (CAT) level in the investigated groups. GM—gentamicin group, GM+SN—gentamicin and Sambucus nigra group, SN—Sambucus nigra group, Control—control group (no treatment).

Figure 6

Glutathione peroxidase (GPX) level in the investigated groups (**** p < 0.0001). GM—gentamicin group, GM+SN—gentamicin and Sambucus nigra group, SN—Sambucus nigra group, Control—control group (no treatment).