ORIGINAL ABSTRACT

Recent debate about the harmful effects of Glyphosate-Based Herbicide (GBH) on human health was noticed. Naringenin (NAR) can enhance various antioxidant and anti-inflammatory mediators. The study aimed to evaluate the possible injurious effects of GBH on the kidney and the prospective ameliorative role of NAR. Thirty-two male Wistar albino rats divided into four groups with eight rats per group were used. GBH and NAR were administered orally once daily, for 14 consecutive days at doses of 100 and 50 mg/kg respectively. Histological, immunohistochemical, morphometrical, molecular and laboratory assessments were performed. GBH supplementation caused glomerular atrophy with occasional hypertrophy and congestion, sloughing of the necrotic epithelium with dilatation and cast formation in the proximal and distal tubules. Cytoplasmic vacuolation, nuclear pyknosis, interstitial atrophy, hemorrhage, inflammatory infiltration, destroyed basement membrane and glomerular mesangium, and massively deposited collagen and amyloid were evident. GBH reduced NrF-2, SLC7A-11, and SLC3A-2 expressions, TAC, CAT, SOD, GSH, IL-10, total protein and albumin and enhanced NF-kβ, Caspase-3, NCOA-4, FTH-1, AKT-1, GSK-3β, ROS, MDA, TNF-α, IL-1β, IL-6, urea, creatinine, and uric acid. NAR exerted reno-protective potential from GBH-induced nephrotoxicity by stabilizing cell survival, metabolism, and proliferation through modulating AKT-1, GSK-3β, and NrF-2 axis which promote the antioxidant response. Also, restored the extrinsic pathway of ferroptosis control by adjusting the downregulated SLC7A-11 and SLC3A-2 and GSH level. In addition, NAR balanced ferritinophagy through correcting NCOA-4 and FTH-1 which rescued cells from ROS generation and iron overload. NAR + GBH might be a competent combination in alleviating GBH-induced nephrotoxicity.