Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium‐induced oxidative challenge, inflammation, and apoptosis in rats

Abstract

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl 2)-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl 2 (6.5 mg/kg), and FA + CdCl 2. CdCl 2 treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl 2-induced oxidative damage through exhausting the cellular defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) and downregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression accompanied by increases of malondialdehyde and nitric oxide contents. Testicular inflammation was evident indicated by increased levels of interleukin-1β and tumor necrosis factor-α in CdCl 2-treated rats. CdCl 2 exposure also decreased the expression of the proliferating cell nuclear antigen and augmented apoptotic events associated with prominent histopathological alterations. However, FA coadministration mitigated the impaired hormonal level, apoptotic and inflammatory injuries elicited by CdCl 2, and maintained the oxidant/antioxidant balance in testicular tissue via Nrf2 activation. Practical applications Cadmium is an environmental toxicant and known to cause adverse effects including reproductive toxicity. However, antioxidant application has been found to protect against heavy metals-mediated toxic effects. Here, we examined the potential protective efficacy of ferulic acid against cadmium-mediated testicular impairments through estimating the amount of cadmium in the testis, hormonal profile, oxidative status, inflammatory response, apoptotic and proliferating markers in addition to the histopathological alterations. The obtained findings revealed that ferulic acid supplementation was able to abolish the testicular damages coupled with cadmium exposure. The protective efficiency of ferulic acid may correlated with its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that ferulic acid may be used to ameliorate cadmium-induced testicular deficits. How to cite this article: Kassab RB, Lokman MS, Daabo HMA, et al. Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats.

Caffeine versus antioxidant combination (Antox) and their role in modifying cadmium‐induced testicular injury in adult male albino rats

“…Ultra-structurally, cellular vacuolisation, alteration of intercellular spacing, elongated spermatids with loss of chromatin condensation and acrosomal alterations have been identified(de Souza Predes et al, 2011), running in agreement with our findings.In accordance with the results of the current study,Kassab et al (2020) confirmed the ability of Cd to induce oxidant/antioxidant imbalance, where the authors reported an elevation in MDA and NO levels and a reduction in GSH level, associated with suppression of antioxidant enzymatic activities of SOD. Similar to our results, Habib et al (2019) observed a significant Cd-induced decrease F I G U R E 17 Mean SOD level (unit/mg protein) among the study groups (a: significant difference in comparison with control group I; b: significant difference in comparison with caffeine sham control group II; c: significant difference in comparison with antox sham control group III; d: significant difference in comparison with cadmium-treated group IV; e: significant difference in comparison with cadmium + caffeine-treated group V; f: significant difference in comparison with cadmium + antioxidant-treated group VI) F I G U R E 1 6 Mean ROS level (ng/mg protein) among the study groups (a: significant difference in comparison with control group I; b: significant difference in comparison with caffeine sham control group II; c: significant difference in comparison with antox sham control group III; d: significant difference in comparison with cadmium-treated group IV; e: significant difference in comparison with cadmium + caffeine-treated group V; f: significant difference in comparison with cadmium + antioxidant-treated group VI) in testicular 3β-HSD and 17β-HSD gene expression.…”

Rosinidin Flavonoid Ameliorates Hyperglycemia, Lipid Pathways and Proinflammatory Cytokines in Streptozotocin-Induced Diabetic Rats

“…The analysis of lipid profile levels in this study specified a promising effect of rosinidin for both dosage regimens. These results are in partial agreement with previous results [ 24 ]. Flavonoids are also regarded as safe for use in the treatment of diabetes-related lipid abnormalities as well as other metabolic illnesses, according to clinical evidence [ 25 ].…”

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities

“… 71 Nrf2 is a transcriptional mediator with cytoprotective impacts mediated by controlling the expression of an array of antioxidant proteins, such as HO-1. 72 The antioxidant activity of Se has been correlated with the incorporation of Se in selenoproteins and selenoenzyme structures, which can dampen ROS and reduce oxidative damage. 73 In accordance with our findings, the treatment of epileptic mice with Se nanoparticles restored neuronal oxidative damage through the upregulation of GR, SOD, GPx, and CAT mRNA expression, increased GSH levels, and reduced MDA and NO generation, 30 which were attributed to the enhancement of antioxidant regulators (Nrf2/HO-1).…”