Sperm and testicular dysfunction during cecal ligation and puncture-induced sepsis in male rats and effects of tannic acid through reducing testicular oxidative stress and inflammation

Document Type : Original Article


1 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Reproductive Biology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


Objective(s): One of the problems caused by infectious diseases is the decrease in sperm count and motility. Tannic acid is known as an anti-oxidant and anti-inflammatory agent. In this study, Cecal Ligation and Puncture (CLP) sepsis model was induced to investigate the effect of tannic acid on oxidative stress and inflammation in testicular and sperm structure and function.
Materials and Methods: Twenty-four male Wistar rats (250–300 g) were randomly divided into 3 groups of 8: 1) sham, 2) sepsis, and 3) sepsis + tannic acid (20 mg/kg at 6, 12, and 24 hr after sepsis induction). Thirty hours after induction of sepsis, testicular samples were collected to measure SOD activity and MDA, IL-6, and TNF-α levels. Another part of the testis was fixed in 10% formalin for histological examinations. 
Results: In the sepsis group, testicular MDA, TNF-α, and IL-6 levels increased and SOD activity decreased compared with the sham group. In addition, the percentage of motile sperm and the survival rate of sperm decreased significantly in the sepsis group. Administration of tannic acid significantly decreased inflammatory markers (TNF-α and IL-6) and MDA levels and increased SOD activity. Furthermore tannic acid significantly improved sperm parameters and increased sperm and animal survival rates.
Conclusion: The results of this study showed that the reproductive system may be strongly affected by the conditions created during sepsis. Tannic acid improved reproductive dysfunction in sepsis by reducing oxidative stress and inflammation.


1. Brunner RJ, Demeter JH, Sindhwani P. Review of guidelines for the evaluation and treatment of leukocytospermia in male infertility. World J Mens Health 2019;37:128-137.
2. Durairajanayagam D, Agarwal A, Ong C. Causes, effects and molecular mechanisms of testicular heat stress. Reprod Biomed Online 2015;30:14-27.
3. Dugar S, Choudhary C, Duggal A. Sepsis and septic shock: Guideline-based management. Cleve Clin J Med 2020;87:53-64.
4. Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Med 2019;7:1-13.
5. Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative stress on testicular function and the role of anti-oxidants in improving it: a review. J Clin Diagn Res 2017;11:1-5.
6. Martin-Hidalgo D, Bragado MJ, Batista AR, Oliveira PF, Alves MG. Anti-oxidants and male fertility: from molecular studies to clinical evidence. Antioxidants 2019;8:89-109.
7. Gülçin İ, Huyut Z, Elmastaş M, Aboul-Enein HY. Radical scavenging and anti-oxidant activity of tannic acid. Arab J Chem 2010;3:43-53.
8. Ramalho-Santos J, Amaral S, Oliveira PJ. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008;4:46-54.
9. Dai X, Zhou L-Y, Xu T-T, Wang Q-Y, Luo B, Li Y-Y, et al. Reproductive responses of the male Brandt’s vole, Lasiopodomys brandtii (Rodentia: Cricetidae) to tannic acid. Zoologia (Curitiba) 2020;37-48.
10. Chen CH, Liu TZ, Chen CH, Wong CH, Chen CH, Lu FJ, et al. The efficacy of protective effects of tannic acid, gallic acid, ellagic acid, and propyl gallate against hydrogen peroxide-induced oxidative stress and DNA damages in IMR-90 cells. Mol Nutr Food Res 2007;51:962-968.
11. Song D, Zhao J, Deng W, Liao Y, Hong X, Hou J. Tannic acid inhibits NLRP3 inflammasome-mediated IL-1β production via blocking NF-κB signaling in macrophages. Biochem Biophys Res Commun 2018;503:3078-3085.
12. Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue III LW, Bland KI, et al. Cecal ligation and puncture. Shock 2005;24:52-57.
13. Esterbauer H, Cheeseman KH. [42] Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990;186:407-421.
14. Mahmood T, Yang P-C. Western blot: technique, theory, and trouble shooting. N Am J Med Sci 2012;4:429-434.
15. Organization WH. World health statistics 2010: World Health Organization; 2010.
16. Abdel-Aziem SH, Hassan AM. Ameliorative Effect of tannic acid against benzo (A) pyrene-induced cytotoxicity and alterations in gene expressions in testicular tissues of rats. Inter J of Cancer Res 2013;47:1118-1152.
17. Long S, Dawe S, Woodward B. Reduced sperm concentration in a patient from a suspected post-operative infection: A case study. Br J Biomed Sci 2020;77:148-151.
18. Karuppagounder V, Arumugam S, Thandavarayan RA, Pitchaimani V, Sreedhar R, Afrin R, et al. Tannic acid modulates NFκB signaling pathway and skin inflammation in NC/Nga mice through PPARγ expression. Cytokine 2015;76:206-213.
19. Zhang J, Cui L, Han X, Zhang Y, Zhang X, Chu X, et al. Protective effects of tannic acid on acute doxorubicin-induced cardiotoxicity: involvement of suppression in oxidative stress, inflammation, and apoptosis. Biomed Pharmacother 2017;93:1253-1260.
20. Soyocak A, Kurt H, Cosan DT, Saydam F, Calis I, Kolac U, et al. Tannic acid exhibits anti-inflammatory effects on formalin-induced paw edema model of inflammation in rats. Hum Exp Toxicol 2019;38:1296-1301.
21. Garami A, Steiner AA, Romanovsky AA. Fever and hypothermia in systemic inflammation. Handb Clin Neurol 2018;157:565-597.
22. Marik P, Zaloga G. Hypothermia and cytokines in septic shock. Intensive Care Med 2000;26:716-721.
23.    Romeo C, Santoro G. Free radicals in adolescent varicocele testis. Oxid Med Cell Longev. 2014;1-5.
24.    Walczak–Jedrzejowska R, Wolski JK, Slowikowska–Hilczer J. The role of oxidative stress and anti-oxidants in male fertility. Cent European J Urol 2013;66:60-67.
25.    Durairajanayagam D, Agarwal A, Ong C, Prashast P. Lycopene and male infertility. Asian J Androl 2014;16:420-425.
26.    Andrade Jr RG, Dalvi LT, Silva Jr JMC, Lopes GK, Alonso A, Hermes-Lima M. The anti-oxidant effect of tannic acid on the in vitro copper-mediated formation of free radicals. Arch Biochem Biophys 2005;437:1-9.
27.    Yang Y, Zhao J, Gao H, Wang R, Li J, Li X, et al. Tannic Acid Alleviates Lipopolysaccharide-Induced H9C2 Cell Apoptosis by Suppressing ROS-Mediated ER Stress. Mol Med Rep 2021;24:1-11.
28.    Mašek T, Starčević K. Lipogenesis and lipid peroxidation in rat testes after long-term treatment with sucrose and tannic acid in drinking water. Andrologia 2017;49:e12632.
29.    Sahoo DK, Roy A, Chainy GB. Protective effects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress. Chem Biol Interact 2008;176:121-128.