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Background and Objective: Obesity has been found to be associated with testicular dysfunction, resulting in decreased sperm quality, testosterone production and consequently male infertility. The aim of this study was to determine the effects of limonin on sperm count and motility and serum testosterone level in obese rats.
Methods: Male Sprague-Dawley rats were divided into the following groups; the control, the diet induced-obesity (Obesity), the obesity treated with limonin at dose 100 mg/kg (LM 100) groups at the last four week of the experiment. At the end of experiment, body weight and retroperitoneal fat were measured. Sperm count and motility measurement was performed. Serum testosterone and testicular MDA level were investigated.
Results: Obesity significantly elevated body weight and fat accumulation while decreased the caudal epididymal sperm concentrations and percentages of sperm motility and serum testosterone compared to the control groups (p < 0.05). Treatment with limonin significantly reduced body weight and fat mass (p < 0.05). An improvement of sperm concentrations and percentages of sperm motility and serum testosterone was observed in LM 100 group (p < 0.01). Testicular MDA significantly increased in Obesity, while limonin treatment significantly diminished testicular MDA level (p < 0.01).
Conclusion: Limonin treatment potentially represents as a supplementation for the prevention of testicular dysfunction induced by obesity.
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Seo CW, Um IC, Rico CW, Kang MY. Antihyperlipidemic and body fat-lowering effects of silk proteins with different fibroin/sericin compositions in mice fed with high fat diet. J Agric Food Chem 2011; 59: 4192-7. doi: 10.1021/jf104812g.
Morrison CD, Brannigan RE. Metabolic syndrome and infertility in men. Best Pract Res Clin Obstet Gynaecol 2015; 29: 507-15. doi: 10.1016/j.bpobgyn.2014.10.006.
Zafar U, Khaliq S, Ahmad HU, Manzoor S, Lone KP. Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links. Hormones 2018; 17: 299-313. doi: 10.1007/s42000-018-0051-3.
Estienne A, Bongrani A, Reverchon M, Ramé C, Ducluzeau PH, Froment P, et al. Involvement of novel adipokines, chemerin, visfatin, resistin and apelin in reproductive functions in normal and pathological conditions in humans and animal models. Int J Mol Sci 2019; 20(18):4431. doi: 10.3390/ijms20184431.
Morgan DH, Ghribi O, Hui L, Geiger JD, Chen X. Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits. Am J Physiol Endocrinol Metab 2014; 307: E1125-30. doi: 10.1152/ajpendo.00416.2014.
Choubey M, Ranjan A, Bora PS, Baltazar F, Krishna A. Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice. Gen Comp Endocrinol 2019; 279: 1-11. doi: 10.1016/j.ygcen.2018.06.002.
Manna P, Jain SK. Obesity, oxidative stress, Adipose tissue dysfunction, and the associated health risks: Causes and Therapeutic Strategies. Metab Syndr Relat Disord 2015; 10: 423-44. doi: 10.1089/met.2015.0095.
Su Z, Wang C, Chang D, Zhu X, Sai C, Pei J. Limonin attenuates the stemness of breast cancer cells via suppressing MIR216A methylation. Biomed Pharmacother 2019; 112: 108699. doi: 10.1016/j.biopha.2019.108699
Yang Y, Wang X, Zhu Q, Gong G, Luo D, Jiang A, et al. Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility. Bioorg Med Chem Lett 2014; 24: 1851-5. doi: 10.1016/j.bmcl.2014.02.003.
Vikram A, Jesudhasan PR, Jayaprakasha GK, Pillai BS, Patil BS. Grapefruit bioactive limonoids modulate E. coli O157:H7 TTSS and biofilm. Int J Food Microbiol 2010; 140: 109-16. doi: 10.1016/j.ijfoodmicro.2010.04.012.
Yang R, Song C, Chen J, Zhou L, Jiang X, Cao X, et al. Limonin ameliorates acetaminophen-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1. Phytomedicine 2020; 69: 153211. doi: 10.1016/j.phymed.2020.153211.
Sun C, KunSong C, Yang C, QingJun C. Contents and antioxidant capacity of limonin and nomilin in different tissues of citrus fruit of four cultivars during fruit growth and maturation. Food Chemistry 2005; 93: 599-605. doi.org/10.1016/j.foodchem.2004.10.037
Ono E, Inoue J, Hashidume T, Shimizu M, Sato R. Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet. Biochem Biophys Res Commun 2011;410: 677-81. doi: 10.1016/j.bbrc.2011.06.055.
Hassan NA, Bassossy HE, Fahmy A, Mahmoud MF. Limonin alleviates macro- and micro-vascular complications of metabolic syndrome in rats: A comparative study with azelnidipine. Phytomedicine 2018; 43: 92-102. doi: 10.1016/j.phymed.2018.03.044.
Wang J, Zhu H, Wang K, Yang Z, Liu Z. Protective effect of quercetin on rat testes against cadmium toxicity by alleviating oxidative stress and autophagy. Environ Sci Pollut Res Int 2020; 27: 25278-86. doi: 10.1007/s11356-020-08947-2.
Ding N, Zhang X, Zhang XD, Jing J, Liu SS, Mu YP, et al. Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes. Gut 2020; 69: 1608-19. doi: 10.1136/gutjnl-2019-319127.
Handelsman DJ. Testosterone, spermatogenesis, and unravelling the mysteries of puberty. Endocrinology 2020; 161. doi: 10.1210/endocr/bqaa120.
Heinrich A, DeFalco T. Essential roles of interstitial cells in testicular development and function. Andrology 2020; 8: 903-14. doi: 10.1111/andr.12703.
Alkafafy ME, Sayed SM, El-Shehawi AM, El-Shazly S, Farouk S, Alotaibi SS, et al. Moringa oleifera ethanolic extract ameliorates the testicular dysfunction resulted from HFD-induced obesityrat model. Andrologia 2021; 53: e14126. doi: 10.1111/and.14126.
Oladele CA, Akintayo CO, Badejogbin OC, Oniyide AA, Omoaghe AO, Agunbiade TB, et al. Melatonin ameliorates endocrine dysfunction and defective sperm integrity associated with high-fat diet-induced obesity in male Wistar rats. Andrologia 2022; 54: e14242. doi: 10.1111/and.14242.
Jiang QC, Maresch, SF, Petry A, Paradowska DS, Bhushan Y, Chang C. Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome. JCI Insight 2020; 5. doi: 10.1172/jci.insight.134882.
Hu X, Ge X, Liang W, Shao Y, Jing J, Wang C, et al. Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis. Syst Biol Reprod Med 2018; 64: 368-80. doi: 10.1080/19396368.2018.1471554.
Wagner IV, Klöting N, Savchuk I, Eifler L, Kulle A, Kralisch-Jäcklein S, J. Dötsch, et al. Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible By Insulin Treatment. Endocrinology 2021; 162. doi: 10.1210/endocr/bqab017.
Yan WJ, Mu Y, Yu N, Yi TL, Zhang Y, Pang XL, et al. Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet. J Assist Reprod Genet 2015;9:097-104 doi: 10.1007/s10815-015-0506-2.
Sedha S, Kumar S, Shukla S. Role of Oxidative Stress in Male Reproductive Dysfunctions with Reference to Phthalate Compounds. Urol J 2015; 12: 2304-16. doi.org/10.22037/uj.v12i5.3009
Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review. J Clin Diagn Res 2017;11:Ie01-ie05. doi: 10.7860/JCDR/2017/23927.9886.
Rahali D, Dallagi Y, Hupkens E, Veegh G, Entee K, Asmi ME, et al. Spermatogenesis and steroidogenesis disruption in a model of metabolic syndrome rats. Arch Physiol Biochem 2020: 1-11. doi: 10.1080/13813455.2020.1812665.
Prasad S, Tiwari M, Pandey AN, Shrivastav TG, Chaube SK. Impact of stress on oocyte quality and reproductive outcome. J Biomed Sci 2016; 23: 1-5. doi: 10.1186/s12929-016-0253-4.
Leisegang L, Kristian A, Henkel R, Agarwal A. Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system. American journal of reproductive immunology 2019; 82: e13178. doi: 10.1111/aji.13178.
Wang D, Zhang H, Fang J, Zhong Y, Yu C. Effects of limoninon on LPS-induced acute lung injury in mice. Chinese Journal of Clinical Pharmacology and Therapeutics 2018; 23: 8. doi: 10.12092/j.issn.1009-2501.2018.01.002
Ishak NM, Mohamed S, Madzuki IN, Mustapha NM. Esa NM. Limonin modulated immune and inflammatory responses to suppress colorectal adenocarcinoma in mice model. Naunyn Schmiedebergs Arch Pharmacol 2021; 394: 1907-15. doi: 10.1007/s00210-021-02101-6.
García-Salas, Patricia, AM, David AR, Antonio SR, Eduardo GH, Belén GV, et al. Influence of technological processes on phenolic compounds, organic acids, furanic derivatives, and antioxidant activity of whole-lemon powder. Food Chemistry 2013; 141: 869-78. doi: 10.1016/j.foodchem.2013.02.124.