Environmental Pollution 302 (2022) 119048 Available online 24 February 2022 0269-7491/© 2022 Elsevier Ltd. All rights reserved. Antioxidative, anti-infammatory and anti-apoptotic action of ellagic acid against lead acetate induced testicular and hepato-renal oxidative damages and pathophysiological changes in male Long Evans rats ☆ Rema Momin Bidanchi, Lalrinsanga Lalrindika, Maurya Khushboo, Baishya Bhanushree, Roy Dinata, Milirani Das, Nisekhoto Nisa, Sailo Lalrinzuali, Bose Manikandan, Laskar Saeed-Ahmed, Sanasam Sanjeev, Meesala Krishna Murthy, Vikas Kumar Roy, Guruswami Gurusubramanian * Department of Zoology, Mizoram University, Aizawl, 796004, Mizoram, India A R T I C L E INFO Keywords: Lead toxicity Ellagic acid Oxidative stress Antioxidant defense Infammation Apoptosis ABSTRACT Lead (Pb), is an environmental toxicant, causes multi-organ dysfunction including reproductive impairments. This study designed to investigate the prospective antioxidative, anti-infammatory and anti-apoptotic effects of ellagic acid (EA) on Pb-mediated testicular and hepato-renal toxicity. Four experimental groups of fve male Long-Evans rats each were used: control, Pb (60 mg/kg), EA (30 mg/kg), and Pb + EA groups. All groups were given their respective treatment orally for 30 days. Pb exposure altered body and organs weight, food and water consumption, rectal temperature, Pb residue levels in tissues, liver and kidney function, sperm quality param- eters, serum metabolic and hematology profles, and impaired the oxidative/antioxidative balance in the testicular and hepato-renal tissue, as shown by the decreased antioxidant proteins (superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione) and increased the oxidative (MDA, lipid hydroper- oxides, conjugated dienes, protein carbonyl, fragmented DNA and GSH:GSSG ratio) stress and infammatory (IL- 1, IL-6, TNF-α, prostaglandin, LTB4, NO, myeloperoxidase, LDH) markers. Moreover, a dysregulation in the stress response (HSP-70) and apoptotic-regulating proteins (BAX, BCL-2, and active Caspase-3) were recorded upon Pb exposure. Remarkably, EA oral administration reduced the Pb residue levels in tissues, improved the liver and kidney function, revived the spermatogenesis and sperm quality, restored redox homeostasis, suppressed the oxidative stress, infammatory and apoptotic responses in the liver, kidney and testis tissue. Our fndings point out that EA can be used as a phyto-chelator to overcome the adverse effects of Pb exposure due to its potent antioxidant, anti-infammatory, and anti-apoptotic effects. 1. Introduction Lead (Pb) has become a global health hazard (0.6%) because of exposure to animals and human beings with ingestion of feed and food, inhalation of industrial emissions, food chain, environment, and water resources (Ericson et al., 2016; Rehman et al., 2018). Globally, blood lead levels of 1 in 3 children (800 million) are estimated to be ≥ 5 μg/dL and over 275 million children in India suffer mild to severe effects of lead poisoning (Rees and Fuller, 2020). Pb is absorbed by the duodenum via DMT1 (divalent metal transporter 1), combined with erythrocyte protein and later dispensed to tissues and organs (García-Ni˜ no and Pedraza-Chaverri, 2014). One third of the total absorbed Pb is stored in the liver due to hepatic conjugation, followed by the kidney and fnally the residual quantity is accumulated in various tissues and organs causing biomolecules (DNA, lipid, protein, RNA) injury, cell damage and cell death (Flora et al., 2006; Chen et al., 2019). Pb is multi-organ cu- mulative toxicants that cause oxidative damage, hemato-biochemical alterations (Al-Omair et al., 2017) and interrupts organ functions causing various metabolic disorders (Caito et al., 2017; Gandhi et al., 2017; Park et al., 2019). Infammation and oxidative stress that play a ☆ This paper has been recommended for acceptance by Wen Chen. * Corresponding author. E-mail address: gurus64@yahoo.com (G. Gurusubramanian). Contents lists available at ScienceDirect Environmental Pollution journal homepage: www.elsevier.com/locate/envpol https://doi.org/10.1016/j.envpol.2022.119048 Received 19 November 2021; Received in revised form 14 February 2022; Accepted 21 February 2022