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Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis

  • Sirui Liu ORCID logo , Jiaxin Wu , Wanqing Liang , Yinkun Liu , Shuangshuang Wan and Shu Tang EMAIL logo
Published/Copyright: December 6, 2024

Abstract

Heat stress impacts male reproduction in animal husbandry. Carnosic acid (CA), a potent antioxidant, mitigates oxidative stress and apoptosis. αB-crystallin, a small heat shock protein, regulates apoptosis and oxidative stress. This study examines the protective effects of CA on the testis in wild-type and αB-crystallin knockout mice under heat stress. CA pretreatment increased testosterone levels and preserved testicular structure in wild-type mice, but no changes in knockout mice. CA reduced Hsp27, Hsp70, and cleaved caspase-3 levels, while knockout mice showed increased cleaved caspase-3. These results suggest that CA protects the testis by modulating heat shock and apoptosis-related proteins.


Corresponding author: Shu Tang, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China, E-mail:

Funding source: the National Key R&D Program of Ningxia Hui Autonomous Region of China

Award Identifier / Grant number: 21BEF02019

Funding source: the National Natural Science Foundation of China

Award Identifier / Grant number: 31602027

Funding source: the Natural Science Foundation of Ningxia Province

Award Identifier / Grant number: 2023AAC05052

  1. Research ethics: All experiments were performed in accordance with the guidelines of the Animal Ethics Committee of Jiangsu Province (China) and were approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University, China.

  2. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Conceptualization, Sirui Liu; Data curation, Yinkun Liu; Investigation, Sirui Liu and Jiaxin Wu; Methodology, Sirui Liu; Software, Jiaxin Wu; Supervision, Shu Tang; Validation, Shuangshuang Wan; Visualization, Wanqing Liang; Writing – original draft, Sirui Liu; Writing – review & editing, Shu Tang.

  3. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  4. Conflict of interest: The authors state no conflict of interest.

  5. Research funding: This work was supported by the Natural Science Foundation of Ningxia Province [grant number 2023AAC05052]; the National Key R&D Program of Ningxia Hui Autonomous Region of China [grant number 21BEF02019]; and the National Natural Science Foundation of China [grant number 31602027].

  6. Data availability: The raw data can be obtained on request from the corresponding author.

References

Aldahhan, R.A. and Stanton, P.G. (2021). Heat stress response of somatic cells in the testis. Mol. Cell. Endocrinol. 527: 111216, https://doi.org/10.1016/j.mce.2021.111216.Search in Google Scholar PubMed

Asadi, M., Taghizadeh, S., Kaviani, E., Vakili, O., Taheri-Anganeh, M., Tahamtan, M., and Savardashtaki, A. (2022). Caspase-3: structure, function, and biotechnological aspects. Biotechnol. Appl. Biochem. 69: 1633–1645, https://doi.org/10.1002/bab.2233.Search in Google Scholar PubMed

Birtić, S., Dussort, P., Pierre, F.-X., Bily, A.C., and Roller, M. (2015). Carnosic acid. Phytochemistry 115: 9–19, https://doi.org/10.1016/j.phytochem.2014.12.026.Search in Google Scholar PubMed

Cao, D., Li, H., Yi, J., Zhang, J., Che, H., Cao, J., Yang, L., Zhu, C., and Jiang, W. (2011). Antioxidant properties of the mung bean flavonoids on alleviating heat stress. PLoS One 6: e21071, https://doi.org/10.1371/journal.pone.0021071.Search in Google Scholar PubMed PubMed Central

Chauhan, S.S., Rashamol, V.P., Bagath, M., Sejian, V., and Dunshea, F.R. (2021). Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration. Int J. Biometeorol 65: 1231–1244, https://doi.org/10.1007/s00484-021-02083-3.Search in Google Scholar PubMed

Claps, G., Faouzi, S., Quidville, V., Chehade, F., Shen, S., Vagner, S., and Robert, C. (2022). The multiple roles of LDH in cancer. Nat. Rev. Clin. Oncol. 19: 749–762, https://doi.org/10.1038/s41571-022-00686-2.Search in Google Scholar PubMed

Davidyan, A., Pathak, S., Baar, K., and Bodine, S.C. (2021). Maintenance of muscle mass in adult male mice is independent of testosterone. PLoS One 16: e0240278, https://doi.org/10.1371/journal.pone.0240278.Search in Google Scholar PubMed PubMed Central

Hu, C., Yang, J., Qi, Z., Wu, H., Wang, B., Zou, F., Mei, H., Liu, J., Wang, W., and Liu, Q. (2022). Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities. MedComm 3: e161, https://doi.org/10.1002/mco2.161.Search in Google Scholar PubMed PubMed Central

Kim, Y., Kim, J., Seo, Y.R., Park, J.H.Y., Choi, M., and Sung, M. (2014). Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity. Mol. Nutr. Food Res. 58: 2274–2285, https://doi.org/10.1002/mnfr.201400293.Search in Google Scholar PubMed

Kocak, C., Kocak, F.E., Akcilar, R., Isiklar, O.O., Kocak, H., Bayat, Z., Simsek, H., Taser, F., and Altuntas, I. (2016). Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life Sci. 147: 15–23, https://doi.org/10.1016/j.lfs.2016.01.038.Search in Google Scholar PubMed

Lang, B.J., Guerrero, M.E., Prince, T.L., Okusha, Y., Bonorino, C., and Calderwood, S.K. (2021). The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response. Arch. Toxicol. 95: 1943–1970, https://doi.org/10.1007/s00204-021-03070-8.Search in Google Scholar PubMed

Lesnak, J.B., Inoue, S., Lima, L., Rasmussen, L., and Sluka, K.A. (2020). Testosterone protects against the development of widespread muscle pain in mice. Pain 161: 2898–2908, https://doi.org/10.1097/j.pain.0000000000001985.Search in Google Scholar PubMed PubMed Central

Li, C., Ye, J., Chen, Q., Hu, W., Wang, L., Fan, Y., Lu, Z., Chen, J., Chen, Z., Chen, S., et al.. (2020). Elevated lactate dehydrogenase (LDH) level as an independent risk factor for the severity and mortality of COVID-19. Aging 12: 15670, https://doi.org/10.18632/aging.103770.Search in Google Scholar PubMed PubMed Central

Paul, C., Murray, A.A., Spears, N., and Saunders, P.T. (2008). A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction 136: 73–84, https://doi.org/10.1530/rep-08-0036.Search in Google Scholar PubMed

Rashamol, V.P., Sejian, V., Bagath, M., Krishnan, G., Archana, P.R., and Bhatta, R. (2018). Physiological adaptability of livestock to heat stress: an updated review. J. Anim. Behav. Biometeorol. 6: 62–71, https://doi.org/10.31893/2318-1265jabb.v6n3p62-71.Search in Google Scholar

Rizzoto, G., Boe-Hansen, G., Klein, C., Thundathil, J.C., and Kastelic, J.P. (2020). Acute mild heat stress alters gene expression in testes and reduces sperm quality in mice. Theriogenology 158: 375–381, https://doi.org/10.1016/j.theriogenology.2020.10.002.Search in Google Scholar PubMed

Robinson, B.R., Netherton, J.K., Ogle, R.A., and Baker, M.A. (2023). Testicular heat stress, a historical perspective and two postulates for why male germ cells are heat sensitive. Biol. Rev. 98: 603–622, https://doi.org/10.1111/brv.12921.Search in Google Scholar PubMed

Saeed, M., Babazadeh, D., Naveed, M., Arain, M.A., Hassan, F.U., and Chao, S. (2017). Reconsidering betaine as a natural anti-heat stress agent in poultry industry: a review. Trop. Anim. Health Prod. 49: 1329–1338, https://doi.org/10.1007/s11250-017-1355-z.Search in Google Scholar PubMed

Shahat, A.M., Rizzoto, G., and Kastelic, J.P. (2020). Amelioration of heat stress-induced damage to testes and sperm quality. Theriogenology 158: 84–96, https://doi.org/10.1016/j.theriogenology.2020.08.034.Search in Google Scholar PubMed

Sun, J., Yin, B., Tang, S., Zhang, X., Xu, J., and Bao, E. (2019). Vitamin C mitigates heat damage by reducing oxidative stress, inducing HSP expression in TM4 Sertoli cells. Mol. Reprod. Dev. 86: 673–685, https://doi.org/10.1002/mrd.23146.Search in Google Scholar PubMed

Thornton, P., Nelson, G., Mayberry, D., and Herrero, M. (2022). Impacts of heat stress on global cattle production during the 21st century: a modelling study. Lancet Planet. Health 6: e192–e201, https://doi.org/10.1016/s2542-5196(22)00002-x.Search in Google Scholar PubMed

Varasteh, S., Braber, S., Akbari, P., Garssen, J., and Fink-Gremmels, J. (2015). Differences in susceptibility to heat stress along the chicken intestine and the protective effects of galacto-oligosaccharides. PLoS One 10: e0138975, https://doi.org/10.1371/journal.pone.0138975.Search in Google Scholar PubMed PubMed Central

Vostakolaei, M.A., Hatami-Baroogh, L., Babaei, G., Molavi, O., Kordi, S., and Abdolalizadeh, J. (2021). Hsp70 in cancer: a double agent in the battle between survival and death. J. Cell. Physiol. 236: 3420–3444, https://doi.org/10.1002/jcp.30132.Search in Google Scholar PubMed

Wasti, S., Sah, N., and Mishra, B. (2020). Impact of heat stress on poultry health and performances, and potential mitigation strategies. Animals 10: 1266, https://doi.org/10.3390/ani10081266.Search in Google Scholar PubMed PubMed Central

Xia, G., Wang, X., Sun, H., Qin, Y., and Fu, M. (2017). Carnosic acid (CA) attenuates collagen-induced arthritis in db/db mice via inflammation suppression by regulating ROS-dependent p38 pathway. Free Radic. Biol. Med. 108: 418–432, https://doi.org/10.1016/j.freeradbiomed.2017.03.023.Search in Google Scholar PubMed

Xiang, Q., Liu, Z., Wang, Y., Xiao, H., Wu, W., Xiao, C., and Liu, X. (2013). Carnosic acid attenuates lipopolysaccharide-induced liver injury in rats via fortifying cellular antioxidant defense system. Food Chem. Toxicol. 53: 1–9, https://doi.org/10.1016/j.fct.2012.11.001.Search in Google Scholar PubMed

Yin, B., Tang, S., Sun, J., Zhang, X., Xu, J., Di, L., Li, Z., Hu, Y., and Bao, E. (2018). Vitamin C and sodium bicarbonate enhance the antioxidant ability of H9C2 cells and induce HSPs to relieve heat stress. Cell Stress Chaperones 23: 735–748, https://doi.org/10.1007/s12192-018-0885-2.Search in Google Scholar PubMed PubMed Central

Zhang, J., Liu, J., Wu, J., Li, W., Chen, Z., and Yang, L. (2019). Progression of the role of CRYAB in signaling pathways and cancers. OncoTargets Ther. 12: 4129–4139, https://doi.org/10.2147/ott.s201799.Search in Google Scholar PubMed PubMed Central

Zhou, Z., Arroum, T., Luo, X., Kang, R., Lee, Y.J., Tang, D., Hüttemann, M., and Song, X. (2024). Diverse functions of cytochrome c in cell death and disease. Cell Death Differ. 31: 387–404, https://doi.org/10.1038/s41418-024-01284-8.Search in Google Scholar PubMed PubMed Central

Received: 2023-12-20
Accepted: 2024-11-25
Published Online: 2024-12-06
Published in Print: 2024-12-17

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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