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Piceatannol inhibits oxidative stress through modification of Nrf2-signaling pathway in testes and attenuates spermatogenesis and steroidogenesis in rats exposed to cadmium during adulthood

Authors Shi X, Fu L

Received 17 December 2018

Accepted for publication 17 April 2019

Published 13 August 2019 Volume 2019:13 Pages 2811—2824

DOI https://doi.org/10.2147/DDDT.S198444

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Georgios D. Panos


Xiaoxue Shi,1 Lijie Fu2

1Department of Urology Surgery, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of China; 2Department of Urological Surgery 2, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, People’s Republic of China

Background: Cadmium (Cd) is considered a heavy metal and potential pollutant to the environment.
Purpose: The purpose of this study was to evaluate the protective potential of piceatannol (PT; 10 mg/kg body weight/day) against cadmium (Cd; 5 mg/kg body weight/day)-induced testicular dysfunction in Wistar rats.
Materials and methods: Rats were randomly divided into four groups: control, PT, Cd, and Cd + PT.
Results: Treatment with Cd resulted in a significant decrease in body, testicular, and epididymal weights, sperm quantity and quality, steroidogenic marker–enzyme activities, mRNA- and protein-expression levels of SF1, StAR, and P450 side chain–cleaving enzyme, and serum male sex hormonal levels when compared to controls. Testicular malondialdehyde levels were significantly increased, with a significant reduction in enzymatic and nonenzymatic antioxidants in Cd-treated rats compared to control rats. Testicular histomorphometric results supported the biochemical and molecular alterations observed in the study. In addition, significant downregulation in mRNA- and protein-expression levels of cytosolic Nrf2, HO1, γGCS, GPx, and NQO1, as well as significant upregulation in mRNA- and protein-expression levels of Nrf2 and Keap1 in testicular tissue, were noticed in rats administered Cd. PT treatment inCd-treated rats caused marked alleviation in body and organ weights, sperm analysis, steroidogenesis, serum hormonal levels, histomorphometric changes, and oxidative and antioxidative status in testes when compared to Cd alone–treated rats. Further, treatment of rats with PTl showed a marked improvement in mRNA- and protein-expression levels of Nrf2 and its regulated genes and proteins.
Conclusion: The present study provides compelling evidence that PT treatment results in significant protection against Cd-induced testicular dysfunctions, such as spermatogenesis, steroidogenesis, and oxidative stress in rats, possibly through modification of the Nrf2–Keap1 signalling pathway.

Keywords: piceatannol, cadmium, steroidogenesis, oxidative stress, Nrf2–Keap1 pathway


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