Cadmium as a testicular toxicant: A Review

Abstract

Cadmium (Cd) is a toxic heavy metal with no known biological functions in the human body. Due to a considerably long biological half-life and very low rate of excretion, accumulation of Cd in different body organs (eg, liver, kidney, and testes) over time is associated with perturbed functioning of these organs. Recent studies have shown the extreme sensitivity of the testes to Cd toxicity. In testes, Cd has been reported to induce oxidative stress, apoptosis of spermatogenic cells, reduction in androgen production and sperm functions. Moreover, Cd in combination with other environmental toxicants may be responsible for the declining fertility of males in both animals and humans. Pinpointing how Cd toxicity affects various testicular processes will be imperative for the development of preventative measures to promote fertility among males. Therefore, in the present review, we summarize the recent findings related to the Cd-induced oxidative toxicity, apoptotic toxicity, steroidogenic toxicity, and spermatotoxicity, along with their possible mechanisms in testicular tissue of different animal species. In addition, the utilization of various antioxidant compounds, medicinal plants and other compounds for the management of Cd toxicity in testes is discussed.

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

“…Testes are particularly sensitive to Cd-induced injury, with the seminiferous epithelium showing morphological and functional changes, often irreversible. It has been suggested that oxidative stress, inflammation, and apoptosis play a central role in detrimental effects brought on by Cd in testes [ 62 ]. Therefore, the use of nutraceuticals able to counteract these damages might be the best preventive/therapeutic approach.…”

Quercetin mediated attenuation of cadmium‐induced oxidative toxicity and apoptosis of spermatogenic cells in caprine testes in vitro

“…However, mounting evidence has recently proved the efficacy of numerous substances with antioxidant capacity in preventing the Cd‐induced testicular damage (Bashir et al ., 2019; Bhardwaj et al ., 2020a; Wang et al ., 2020). In the present study, co‐incubation with Qcn provides significant protection to the Cd‐induced oxidative stress in testis by inhibiting the lipid peroxidation (decrease in MDA level), and restoring the Cd‐induced reduction in total antioxidant capacity (FRAP activity) with the simultaneous restoration of antioxidant enzymes' (CAT, SOD, GST) activity.…”

“…Among the complexity of factors involved in Cd‐induced testicular pathogenesis, oxidation‐mediated toxicity represents the main reason. Numerous studies have demonstrated the involvement of oxidative stress in Cd‐induced testicular injury (Almeer et al ., 2018; Bhardwaj et al ., 2020a). In testes, Cd‐induced oxidative damage occurs via excessive generation of free radicals, enhanced lipid peroxidation, and alteration in the activities of endogenous antioxidant enzymes, eventually endangering male fertility (Bashir et al ., 2019; Elmallah et al ., 2017; Erboga et al ., 2016).…”

“…In testes, Cd‐induced oxidative damage occurs via excessive generation of free radicals, enhanced lipid peroxidation, and alteration in the activities of endogenous antioxidant enzymes, eventually endangering male fertility (Bashir et al ., 2019; Elmallah et al ., 2017; Erboga et al ., 2016). In recent times, studies have been exploring the use of numerous antioxidant compounds for managing the Cd‐mediated oxidative toxicity in testes (Bhardwaj et al ., 2020a; Mitra et al ., 2016).…”

Activation of Nrf2/HO‐1 signaling pathway attenuates ROS‐mediated autophagy induced by silica nanoparticles in H9c2 cells

“…It has been well established that Nrf2 is activated under stress conditions caused by ROS or electrophiles 50,51 and plays a key role in cell protection. Nrf2 can bind to ARE in the nucleus and activate genes regulated by oxidative response elements, including endogenous antioxidants (SOD, CAT, GSH-PX), phase II detoxification enzymes (GCL, NADPH, HO-1), and so on.…”