Received: 30 December 2016 Revised: 15 March 2017 Accepted: 20 March 2017 DOI: 10.1002/jbt.21928 Investigation of the effect of naringenin on oxidative stress-related alterations in testis of hydrogen peroxide-administered rats Zafer Sahin 1,2 Ahmet Ozkaya 3 Gokhan Cuce 4 Mirac Uckun 5 Ertan Yologlu 6 1 Department of Physiotherapy and Rehabili- tation, Faculty of Health Sciences, Necmettin Erbakan University, Konya, Turkey 2 KONÜDAM Experimental Medicine Applica- tion and Research Center, Necmettin Erbakan University, Konya, Turkey 3 Department of Chemistry, Faculty of Science and Art, Adiyaman University, Adiyaman, Turkey 4 Department of Histology and Embryology, Faculty of Meram Medicine, Necmettin Erbakan University, Konya, Turkey 5 Department of Food Engineering, Faculty of Engineering, Adiyaman University, Adiyaman, Turkey 6 Department of Science Education, Faculty of Education, Adiyaman University, Adiyaman, Turkey Correspondence Zafer Sahin. (E-mail: zafersahin@konya.edu.tr) Contract Grant Sponsor: The Scientific Research Projects Unit of Adiyaman Univer- sity (ADYUBAP). This Funding agency is an local unit of the Adiyaman University. Contract Grant Number: FEFYL 2013/0005. Abstract Testis tissue is prone to oxidation because its plasma membrane contains many polyunsaturated fatty acids. Naringenin is a plant-derived natural flavonoid. We investigated the possible amelio- rative role of naringenin on the hydrogen peroxide (H 2 O 2 )-induced testicular damage in Wistar rats. Animals received 12 mg/kg H 2 O 2 by intraperitoneal injection, and 50 mg/kg naringenin via orogastric gavage for 4 weeks. In the H 2 O 2 group, the testis malondialdehyde level increased, while the amount of reduced glutathione, glutathione transferase activities, and the testis weight decreased. There were severe testicular damages in the H 2 O 2 group otherwise their grade were less in the naringenin + H 2 O 2 group. However, the serum testosterone concentrations decreased in both the H 2 O 2 and the naringenin + H 2 O 2 groups. The testicular zinc and calcium levels reduced in the H 2 O 2 -treated rats. In conclusion, the administration of H 2 O 2 caused oxidative stress in the testes and naringenin supplementation decreased the H 2 O 2 -induced effects, except for changes in testosterone levels. KEYWORDS hydrogen peroxide, naringenin, oxidative stress, testosterone, testis 1 INTRODUCTION Although fertility may decrease with the increasing age, infertil- ity often occurs as a result of reproductive dysfunction and this is more common in males than in females. [1,2] Approximately 20% of these patients have endocrine abnormality involving testosterone and follicle-stimulating hormone (FSH) deficiencies. [2] Several recent reports asserted that oxidative stress-related alterations might have a role in the pathophysiology of male reproductive disorders or infertility. [3–6] Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and enzymatic–non- enzymatic antioxidant defense in any tissue. [5] ROS are a group of free radicals, reactive molecules, and ions that are derived from O 2 . Superoxide anion (O 2 – ), hydroxyl radical (⋅OH), and hydrogen peroxide (H 2 O 2 ) are members of ROS, but H 2 O 2 , which contains no unpaired electrons, is not considered strictly a free radical. [7,8] However, H 2 O 2 is accepted as a ROS because of its ability to generate highly reac- tive hydroxyl free radicals through interactions with reactive transi- tion metals like iron (Fe) and copper (Cu). [7,9,10] Essential elements such as calcium (Ca), magnesium (Mg), zinc (Zn), chromium (Cr), manganese (Mn), and Cu are necessary for many metabolic processes in humans and animals. [11] Of these elements, transition metals like Zn, Cu, and Mn play major roles in male reproductive system, and deficiency of these trace metals may have a negative effect on fertility. [12] In partic- ular, Zn deficiency leads to gonadal dysfunction, decreased testicular weight, and shrinkage of the seminiferous tubules. [13] The plasma membrane of testicular cells is rich in polyunsaturated fatty acids and thus prone to oxidation by H 2 O 2 and other ROS. [14] The generation of ROS is inevitable in aerobic metabolism of the body, and several studies suggest that low levels of endogenous ROS are required for the regulation of vital sperm functions, such as capacita- tion, the acrosome reaction, and sperm-oocyte fusion. [15,16] However, germinal sperm cells are very sensitive and easily compromised by high ROS levels. [3] Therefore, free radical-scavenging/antioxidant system is critical for maintaining the redox balance in the male reproductive system. [17] J Biochem Mol Toxicol. 2017;e21928. c  2017 Wiley Periodicals, Inc. 1 of 6 wileyonlinelibrary.com/journal/jbt https://doi.org/10.1002/jbt.21928