<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Abstract

Introduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation. Materials and Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks. Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pbinduced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats. Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.

Vitamin D3 Protects Mice from Diquat-Induced Oxidative Stress through the NF-κB/Nrf2/HO-1 Signaling Pathway

“…Nrf2 is a crucial protein playing a key role in cellular defense against oxidative stress as the transcription factor [30]. It could effectively enhance the expression of antioxidant-related genes through binding to the antioxidant response elements (ARE) [31,32].…”

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

“…Lead (Pb) is an omnipresent toxic metal widely used in industry and found not only in environmental air, dust, foods, and drinking water but also in various products such as cosmetics, toys, paints, shot bullets, fishing weights, and lead-acid batteries [ 82 ]. Lead is recognized as an environmental pollutant threatening human health, even in low doses, and causing severe neurological, hematological, gastrointestinal, immunological, cardiovascular, and reproductive disorders [ 82 , 83 , 84 ].…”

“…Lead (Pb) is an omnipresent toxic metal widely used in industry and found not only in environmental air, dust, foods, and drinking water but also in various products such as cosmetics, toys, paints, shot bullets, fishing weights, and lead-acid batteries [ 82 ]. Lead is recognized as an environmental pollutant threatening human health, even in low doses, and causing severe neurological, hematological, gastrointestinal, immunological, cardiovascular, and reproductive disorders [ 82 , 83 , 84 ]. The results of both in vitro and in vivo studies have shown that exposure to Pb can be linked to a decreased antioxidant enzymes activity and expression, while authors have suggested the potential relationship with Nrf2 signaling [ 28 , 85 ].…”

“…In the same study, Pb exposure downregulated Nfe2l2 and HO-1 mRNA expression and amplified the levels of inflammatory markers (TNF-α, IL-1β, and NO) in renal tissue, which were upregulated [ 28 ]. Downregulated gene expression of Nrf2, NQO-1, and HO-1 could be seen in the rat testis as well resulting in oxidative damage, inflammation, and cell death [ 82 ]. Moreover, inhibition of Nrf2 and HO-1 activation, coupled with the decreased nuclear translocation of Nrf2 in mice brain, could be connected with oxidative stress, inflammation, and apoptosis of neurons in hippocampus tissue extracted from mice after 4-week Pb treatment [ 86 ].…”

Effects of Itxasol© Components on Gene Expression in Bacteria Related to Infections of the Urinary Tract and to the Inflammation Process

“…Umb has also demonstrated anti-tumor and anti-arthritic activities due to its antioxidant and anti-inflammatory properties, as shown by multiple studies supporting these characteristics [ 46 , 47 , 64 , 65 ]. Related to its anti-inflammatory activity, Umb has shown in an in vivo study with lead-treated rats that it is capable of attenuating the damage to DNA due to oxidative stress and that it is capable of reducing the gene expression of genes such as BAX, while increasing that of BCL-2 [ 62 ]. All of this led to a reduction of lead-mediated testicular damage in this animal model.…”