Luteolin protects against testicular injury induced by lead acetate by activating the Nrf2/HO‐1 pathway

Abstract

Lead (Pb) is a toxic heavy metal that is harmful to humans, especially male reproductive organs. Luteolin (LUT) is a naturally occurring flavonoid with numerous biological activities. Our aim was to investigate the possible reproprotective effect of LUT against testicular deficits induced by Pb intoxication. In the present study, 28 rats were distributed into 4 groups: control, LUT (50 mg/kg), lead acetate (PbAc, 20 mg/kg), and LUT + PbAc groups, in which rats were pre‐treated with LUT 3 hr before PbAc injection. All animals were treated for 7 days. Oxidative stress, inflammatory and apoptotic markers along with histopathological changes have been examined using spectrophotometric, ELISA, real‐time PCR, and histopathological methods. PbAc injection elevated Pb concentration in testicular tissue and decreased levels of sex hormones. PbAc intoxication exacerbated lipoperoxidation and nitric oxide formation, depleted superoxide dismutase, and catalase activities along with glutathione and its originated enzymes (glutathione peroxidase and glutathione reductase). At the molecular level, PbAc deactivated nuclear factor erythroid 2‐related factor 2 and heme oxygenase‐1 in the testicular tissue. In addition, PbAc toxicity induced inflammatory and apoptotic cascades in testicular tissue as evidenced by the increased tumor necrosis factor‐alpha, interleukin‐1 beta, inducible nitric oxide synthase, Bax, and caspase 3, while Bcl‐2 was declined. Histopathological examination of testicular tissue also revealed that PbAc caused degeneration alterations in spermatogenic cells, the spermatogenic epithelial cells were disconnected from the basement membrane, and the seminiferous tubules were vacuolated. Remarkably, pre‐treatment with LUT minimized significantly the testicular damage induced by PbAc. Therefore, we conclude that LUT may have a beneficial effect against PbAc‐induced testicular injury through preventing oxidative challenge, inflammation, and finally apoptosis.

Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti‐inflammatory, and antiapoptotic properties

“…Spermatozoa have a high content of polyunsaturated fatty acids. Therefore, it is thought to be extremely sensitive to reactive oxygen species (AL‐Megrin et al., 2020; El‐Khadragy et al, 2020). Oxidative stress plays an important role in the formation of Pb toxicity by damaging sperm membranes, proteins, and DNA (Ezejiofor & Orisakwe, 2019).…”

“…According to the previous studies, it has been reported that PbAc suppresses the antioxidant defense system and causes lipid peroxidation. (Abdrabou et al., 2019; AL‐Megrin et al, 2020; Rao et al., 2016). In the present study, it was detected that PbAc weakened antioxidant defense and resulted in lipid peroxidation.…”

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

“…The authors observed nuclear translocation of Nrf2, along with the dose-dependent decrease in GST and GSH, suggesting that the multidrug resistance protein 1 (Mrp1), which was also upregulated upon Pb exposure, might play important roles in lead detoxification by Nrf2 [ 89 ]. The authors speculated that overactivation of nuclear factor kappa B (NF-κB) by free radical overproduction increased the level of Keap1, leading to Nrf2 impairment and a decrease in its antioxidant effects [ 90 ].…”

Effects of Traditional Chinese Medication‐Based Bioactive Compounds on Cellular and Molecular Mechanisms of Oxidative Stress

“…Luteolin exhibits antioxidative property in lipopolysaccharide-stimulated murine macrophages through transforming growth factor betaactivated kinase 1 TAK1 inhibition and Nrf2 activation [66]. Luteolin also enhances the antioxidative process in intracerebral hemorrhage and testicular injury by activating the p62-Keap1-Nrf2 [67] or Nrf2/HO-1 pathway [68]. Moreover, p21 upregulation and mTOR signaling inhibition are involved in the antioxidant effect of luteolin [69].…”