Antioxidant Effects of Moringa oleifera Against Abamectin‐Induced Oxidative Stress in the Brain and Erythrocytes of Rats

ABSTRACT The current study was conducted to explore the phytochemical composition and in vitro antioxidant activity of Moringa oleifera leaves aqueous extract (MOLE), as well as its in vivo modulatory effects on abamectin (ABM)‐induced oxidative stress in rat erythrocytes and brain tissue. Following extraction, the total phenolic, flavonoid, condensed tannin and ortho ‐diphenolic contents of MOLE were determined. High‐performance liquid chromatography (HPLC) analysis allowed the identification and the quantification of 12 bioactive compounds: gallic acid, chlorogenic acid, caffeic acid, vanillic acid, quercetin, ferulic acid, ascorbic acid, alizarin, hesperidin, neohesperidin, resveratrol, and naringin. In vitro study: the assessment of the antioxidant activity of MOLE on the 2,2‐diphenyl‐1‐picrylhydrazyl radical DPPH and the 2,2ʹ‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radical cation (ABTS), its ferric reducing power and its antioxidant effect on the β‐carotene bleaching indicated that MOLE exhibited potent antioxidant activity, with an IC 50 of 0.125 mg/mL against DPPH radical, and an IC 50 of 0.06 mg/mL against ABTS radical. It also demonstrated notable ferric‐reducing ability, with an EC 50 of 1.4 mg/mL and a strong inhibition of β‐carotene bleaching with an IC 50 of 1.36 mg/mL. In vivo study: Twenty rats were equally divided into four groups. The first group served as a control and received distilled water by gavage. The second group (negative control) received ABM in drinking water at a dose of 1 mg/kg body weight. The third group received MOLE at a dose of 200 mg/kg of body weight by gavage. The fourth group received a combination of ABM and MOLE in the same manner and doses as described, for 3 weeks. Body weight, brain relative and absolute weights, and nitric oxide levels were not affected by ABM. However, ABM significantly inhibited acetylcholinesterase (AChE) activity ( p  < 0.001), decreased the activities of antioxidant enzymes, specifically superoxide dismutase (SOD) and glutathione S‐transferase (GST) in cerebral tissue, and catalase (CAT) in erythrocytes ( p  < 0.001). ABM also decreased reduced glutathione (GSH) levels in both the brain ( p  < 0.001) and erythrocytes ( p  < 0.05). In addition, malondialdehyde (MDA) levels significantly increased in the brains of ABM‐intoxicated rats ( p  < 0.01) compared to the control group. These results were accompanied by histopathological changes, notably the remarkable vacuolization of neuropil in brain tissue. Supplementation with MOLE in ABM‐treated rats significantly ameliorated brain AChE ( p  < 0.05) and GST activities, decreased MDA content, and improved GSH levels in both brain and erythrocyte homogenates ( p  < 0.01). MOLE also restored the histopathological alterations observed in the ABM group. Computational modeling revealed that some of the tested molecules, including some present in the studied extract, bound human peroxiredoxin 5, CAT, and glutathione peroxidase with acceptable affinities, which, together with the established molecular interactions and tight embedding satisfactory support the in vivo results. Thus, it may be concluded that ABM impairs brain and erythrocyte function through oxidative damage, and these effects could be prevented by MOLE, likely due to its antioxidant activity.