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

Rami B Kassab; Maha S Lokman; Hamid M A Daabo; Dalia A Gaber; Ola A Habotta; Mohamed M Hafez; Ahmed S Zhery; Ahmed E Abdel Moneim; Manar S Fouda

doi:10.1111/jfbc.13505

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

J Food Biochem. 2020 Dec;44(12):e13505. doi: 10.1111/jfbc.13505. Epub 2020 Oct 12.

Authors

Rami B Kassab^{1

2}, Maha S Lokman³, Hamid M A Daabo⁴, Dalia A Gaber⁵, Ola A Habotta⁶, Mohamed M Hafez⁷, Ahmed S Zhery⁸, Ahmed E Abdel Moneim¹, Manar S Fouda⁹

Affiliations

¹ Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
² Department of Biology, Faculty of Science and Arts, Al Baha University, Al Baha, Saudi Arabia.
³ Biology Department, College of Science and Humanities, Prince Sattam bin Abdul Aziz University, Alkharj, Saudi Arabia.
⁴ Pharmacy Department, Duhok Technical Institute, Duhok Polytechnic University, Duhok, Iraq.
⁵ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
⁶ Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁷ Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University (ACU), Giza, Egypt.
⁸ Kasr Al-Eini School of Medicine, Cairo University, Cairo, Egypt.
⁹ Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt.

PMID: 33047361
DOI: 10.1111/jfbc.13505

Abstract

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl₂ )-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl₂ (6.5 mg/kg), and FA + CdCl₂ . CdCl₂ treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl₂ -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 CdCl₂ -treated rats. CdCl₂ 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.

Keywords: Nrf2; cadmium; ferulic acid; oxidative stress; rats; reproductive toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cadmium* / toxicity
Coumaric Acids
Inflammation
Male
NF-E2-Related Factor 2* / metabolism
Oxidative Stress
Rats

Substances

Coumaric Acids
NF-E2-Related Factor 2
Cadmium
ferulic acid