دورية أكاديمية

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

التفاصيل البيبلوغرافية
العنوان: Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.
المؤلفون: Saleh DO; Pharmacology Department, National Research Centre, Giza, 12622, Egypt. doabdelfattah@yahoo.com., Baraka SM; Chemistry of Natural Compounds Department, National Research Centre, Giza, 12622, Egypt., Jaleel GAA; Pharmacology Department, National Research Centre, Giza, 12622, Egypt., Hassan A; Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt., Ahmed-Farid OA; Physiology Department, National Organization for Drug Control and Research, Giza, Egypt.
المصدر: Scientific reports [Sci Rep] 2024 Jan 22; Vol. 14 (1), pp. 1910. Date of Electronic Publication: 2024 Jan 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Testis* , Antifibrinolytic Agents*, Male ; Animals ; Rats ; AMP-Activated Protein Kinases ; Eugenol/pharmacology ; Proto-Oncogene Proteins c-akt ; Blood-Testis Barrier ; Phosphatidylinositol 3-Kinases ; Semen ; Signal Transduction ; TOR Serine-Threonine Kinases ; Acrylamide/toxicity ; Amino Acids ; Mammals
مستخلص: This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.
(© 2024. The Author(s).)
References: Boettcher, M. I., Schettgen, T., Kütting, B., Pischetsrieder, M. & Angerer, J. Mercapturic acids of acrylamide and glycidamide as biomarkers of the internal exposure to acrylamide in the general population. Mutat. Res./Genet. Toxicol. Environ. Mutagen. 580, 167–176 (2005). (PMID: 10.1016/j.mrgentox.2004.11.010)
Friedman, M. Acrylamide: Inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans. Food Funct. 6, 1752–1772 (2015). (PMID: 2598936310.1039/C5FO00320B)
Doerge, D. R., Young, J. F., Chen, J. J., DiNovi, M. J. & Henry, S. H. Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity. J. Agric. Food Chem. 56, 6031–6038 (2008). (PMID: 1862443510.1021/jf073042g)
Hagmar, L. et al. Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose. Scand. J. Work Environ. Health 27, 219–226 (2001). (PMID: 1156033510.5271/sjweh.608)
Joint, F., Organization, W. H. & Additives, W. E. C. o. F. Evaluation of certain contaminants in food: seventy-second [72nd] report of the Joint FAO/WHO Expert Committee on Food Additives. (World Health Organization, 2011).
Goudarzi, M. et al. Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol. Res. 41, 419–428 (2019). (PMID: 3073510210.1080/01616412.2019.1576319)
Pan, X. et al. Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs. Toxicol. Lett. 288, 55–64 (2018). (PMID: 2942600210.1016/j.toxlet.2018.02.002)
LoPachin, R. M. & Gavin, T. Acrylamide-induced nerve terminal damage: Relevance to neurotoxic and neurodegenerative mechanisms. J. Agric. Food Chem. 56, 5994–6003 (2008). (PMID: 1862443710.1021/jf703745t)
Raldúa, D. et al. Targeting redox metabolism: The perfect storm induced by acrylamide poisoning in the brain. Sci. Rep. 10, 312 (2020). (PMID: 31941973696217010.1038/s41598-019-57142-y)
Settels, E. et al. Human CYP2E1 mediates the formation of glycidamide from acrylamide. Arch. Toxicol. 82, 717–727 (2008). (PMID: 1841858010.1007/s00204-008-0296-8)
Farag, O. M. et al. Portulaca oleracea seeds’ extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats. BMC Complement. Med. Ther. 21, 1–15 (2021). (PMID: 10.1186/s12906-021-03286-2)
Kucukler, S., Caglayan, C., Darendelioğlu, E. & Kandemir, F. M. Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sci. 261, 118301 (2020). (PMID: 3282754610.1016/j.lfs.2020.118301)
Yilmaz, B. O., Yildizbayrak, N., Aydin, Y. & Erkan, M. Evidence of acrylamide- and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells. Hum. Exp. Toxicol. 36, 1225–1235. https://doi.org/10.1177/0960327116686818 (2017). (PMID: 10.1177/096032711668681828067054)
Song, H. X., Wang, R., Geng, Z. M., Cao, S. X. & Liu, T. Z. Subchronic exposure to acrylamide affects reproduction and testis endocrine function of rats. Zhonghua nan ke xue Natl. J. Androl. 14, 406–410 (2008).
Hamdy, S. M., Bakeer, H. M., Eskander, E. F. & Sayed, O. N. Effect of acrylamide on some hormones and endocrine tissues in male rats. Hum. Exp. Toxicol. 31, 483–491. https://doi.org/10.1177/0960327111417267 (2012). (PMID: 10.1177/096032711141726721878450)
Zhang, P., Zhang, E., Xiao, M., Chen, C. & Xu, W. Study of anti-inflammatory activities of α-d-glucosylated eugenol. Arch. Pharm. Res. 36, 109–115 (2013). (PMID: 2332549010.1007/s12272-013-0003-z)
Navikaite-Snipaitiene, V. et al. Development of antioxidant food packaging materials containing eugenol for extending display life of fresh beef. Meat Sci. 145, 9–15 (2018). (PMID: 2985942210.1016/j.meatsci.2018.05.015)
Dai, J.-P. et al. Drug screening for autophagy inhibitors based on the dissociation of Beclin1-Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity. PLoS ONE 8, e61026 (2013). (PMID: 23613775362888910.1371/journal.pone.0061026)
Hamed, S. F., Sadek, Z. & Edris, A. Antioxidant and antimicrobial activities of clove bud essential oil and eugenol nanoparticles in alcohol-free microemulsion. J. Oleo Sci. 61, 641–648 (2012). (PMID: 2313825310.5650/jos.61.641)
Han, X. & Parker, T. L. Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm. Biol. 55, 1619–1622 (2017). (PMID: 28407719613073410.1080/13880209.2017.1314513)
Taher, Y. A. et al. Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice. Libyan J. Med. 10, 28685 (2015). (PMID: 2633387310.3402/ljm.v10.28685)
Anuj, G. & Sanjay, S. Eugenol: A potential phytochemical with multifaceted therapeutic activities. Pharmacologyonline 2, 108–120 (2010).
Irie, Y. Effects of eugenol on the central nervous system: Its possible application to treatment of Alzheimer’s disease, depression, and Parkinson’s disease. Curr. Bioactive Compd. 2, 57–66 (2006). (PMID: 10.2174/1573407210602010057)
Kaur, G., Athar, M. & Alam, M. S. Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis. Mol. Carcinog. 49, 290–301 (2010). (PMID: 2004329810.1002/mc.20601)
Rahangadale, S. et al. Evaluation of protective effect of vitamin e on acrylamide induced testicular toxicity in wister rats. Toxicol. Int. 19, 158 (2012). (PMID: 22778514338876010.4103/0971-6580.97216)
Sun, X. et al. Eugenol attenuates cerebral ischemia–reperfusion injury by enhancing autophagy via AMPK-mTOR-P70S6K pathway. Front. Pharmacol. 11, 84 (2020). (PMID: 32153404704721110.3389/fphar.2020.00084)
Struck, M. B., Andrutis, K. A., Ramirez, H. E. & Battles, A. H. Effect of a short-term fast on ketamine–xylazine anesthesia in rats. J. Am. Assoc. Lab. Anim. Sci. 50, 344–348 (2011). (PMID: 216400293103284)
Heidari, R. et al. Do Pilea microphylla improve sperm DNA fragmentation and sperm parameters in varicocelized rats?. Acta Medica Iranica 53, 547–554 (2015). (PMID: 26553082)
Sánchez-Álvarez, J., Cano-Corres, R. & Fuentes-Arderiu, X. A complement for the WHO laboratory manual for the examination and processing of human semen (2010). Ejifcc 23, 103 (2012). (PMID: 276834234975259)
Wyrobek, A. & Bruce, W. Chemical induction of sperm abnormalities in mice. Proc. Natl. Acad. Sci. 72, 4425–4429 (1975). (PMID: 106012238873410.1073/pnas.72.11.4425)
Saunders, J., Saunders, J., Morris, S. & Wynne, S. Amino acid analysis of subcellular fractions by PITC and OPA. Chromatogram 9, 2–4 (1988).
Liu, H., Jiang, Y., Luo, Y. & Jiang, W. A simple and rapid determination of ATP, ADP and AMP concentrations in pericarp tissue of litchi fruit by high performance liquid chromatography. Food Technol. Biotechnol. 44, 531–534 (2006).
Pradet, A. & Raymond, P. Adenine nucleotide ratios and adenylate energy charge in energy metabolism. Annu. Rev. Plant Physiol. 34, 199–224 (1983). (PMID: 10.1146/annurev.pp.34.060183.001215)
Folch, J., Lees, M. & Stanley, G. H. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509. https://doi.org/10.1016/S0021-9258(18)64849-5 (1957). (PMID: 10.1016/S0021-9258(18)64849-513428781)
Jayatilleke, E. & Shaw, S. A high-performance liquid chromatographic assay for reduced and oxidized glutathione in biological samples. Anal. Biochem. 214, 452–457 (1993). (PMID: 810973310.1006/abio.1993.1522)
Yoshida, T. Determination of reduced and oxidized glutathione in erythrocytes by high-performance liquid chromatography with ultraviolet absorbance detection. J. Chromatogr. B Biomed. Sci. Appl. 678, 157–164 (1996). (PMID: 10.1016/0378-4347(95)00489-0)
Lazzarino, G., Di Pierro, D., Tavazzi, B., Cerroni, L. & Giardina, B. Simultaneous separation of malondialdehyde, ascorbic acid, and adenine nucleotide derivatives from biological samples by ion-pairing high-performance liquid chromatography. Anal. Biochem. 197, 191–196 (1991). (PMID: 195206510.1016/0003-2697(91)90378-7)
Papadoyannis, I., Samanidou, V. & Nitsos, C. C. Simultaneous determination of nitrite and nitrate in drinking water and human serum by high performance anion-exchange chromatography and UV detection. J. Liq. Chromatogr. Relat. Technol. 22, 2023–2041 (1999). (PMID: 10.1081/JLC-100101783)
Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976). (PMID: 94205110.1016/0003-2697(76)90527-3)
Lanning, L. L. et al. Recommended approaches for the evaluation of testicular and epididymal toxicity. Toxicol. Pathol. 30, 507–520 (2002). (PMID: 1218794210.1080/01926230290105695)
Shapiro, S. S. & Wilk, M. B. An analysis of variance test for normality (complete samples). Biometrika 52, 591–611 (1965). (PMID: 10.1093/biomet/52.3-4.591)
Kuorwel, K., Lumori, C. & Andrew, A. Review of South sudans food safety status in relation to chemical contaminants. MOJ Food Process. Technol 6, 00153 (2018). (PMID: 10.15406/mojfpt.2018.06.00153)
Lebda, M., Gad, S. & Gaafar, H. Effects of lipoic acid on acrylamide induced testicular damage. Materia socio-medica 26, 208 (2014). (PMID: 25126019413068710.5455/msm.2014.26.208-212)
Yang, H. J. et al. Genotoxicity and toxicological effects of acrylamide on reproductive system in male rats. J. Vet. Sci. 6, 103–109 (2005). (PMID: 1593342910.4142/jvs.2005.6.2.103)
Ou, C. & Uo, D. Effects of acrylamide on the reproductive hormones and sperm quality in male rats. Int. J. Sci. Res. 6, 5–8 (2015).
Tyl, R. W. & Friedman, M. A. Effects of acrylamide on rodent reproductive performance. Reprod. Toxicol. 17, 1–13 (2003). (PMID: 1250765310.1016/S0890-6238(02)00078-3)
Tyl, R. W., Marr, M. C., Myers, C. B., Ross, W. P. & Friedman, M. A. Relationship between acrylamide reproductive and neurotoxicity in male rats. Reprod. Toxicol. 14, 147–157 (2000). (PMID: 1082567810.1016/S0890-6238(00)00066-6)
Adler, I.-D., Baumgartner, A., Gonda, H., Friedman, M. & Skerhut, M. 1-Aminobenzotriazole inhibits acrylamide-induced dominant lethal effects in spermatids of male mice. Mutagenesis 15, 133–136 (2000). (PMID: 1071903810.1093/mutage/15.2.133)
O'Donnell, L., Stanton, P. & de Kretser, D. M. Endocrinology of the male reproductive system and spermatogenesis. (2015).
Ekinci Akdemir, F. N. et al. The antiapoptotic and antioxidant effects of eugenol against cisplatin-induced testicular damage in the experimental model. Andrologia 51, e13353 (2019). (PMID: 3124380010.1111/and.13353)
Baba, S. P. & Bhatnagar, A. Role of thiols in oxidative stress. Curr. Opin. Toxicol. 7, 133–139 (2018). (PMID: 30338308618863710.1016/j.cotox.2018.03.005)
Sanocka, D. & Kurpisz, M. Reactive oxygen species and sperm cells. Reprod. Biol. Endocrinol. 2, 1–7 (2004). (PMID: 10.1186/1477-7827-2-12)
Dilber, Y., Inan, S., Ercan, G. A. & Sencan, A. The role of CAPE in PI3K/AKT/mTOR activation and oxidative stress on testis torsion. Acta Histochem. 118, 31–37 (2016). (PMID: 2665195310.1016/j.acthis.2015.11.004)
Wang, H., Wang, J., Zhang, J., Jin, S. & Li, H. Role of PI3K/AKT/mTOR signaling pathway in DBP-induced apoptosis of testicular sertoli cells in vitro. Environ. Toxicol. Pharmacol. 53, 145–150 (2017). (PMID: 2857814410.1016/j.etap.2017.05.013)
Jhanwar-Uniyal, M. et al. Discrete signaling mechanisms of mTORC1 and mTORC2: Connected yet apart in cellular and molecular aspects. Adv. Biol. Regul. 64, 39–48 (2017). (PMID: 2818945710.1016/j.jbior.2016.12.001)
Mok, K.-W., Chen, H., Lee, W. M. & Cheng, C. Y. rpS6 regulates blood–testis barrier dynamics through Arp3-mediated actin microfilament organization in rat Sertoli cells. An in vitro study. Endocrinology 156, 1900–1913 (2015). (PMID: 25714812439876110.1210/en.2014-1791)
Mok, K.-W., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Rictor/mTORC2 regulates blood–testis barrier dynamics via its effects on gap junction communications and actin filament network. FASEB J. 27, 1137 (2013). (PMID: 23288930357427910.1096/fj.12-212977)
Yang, L., Zhang, Y., Yan, Z. & Tian, F. The role of mTOR signaling pathway on cognitive functions in cerebral ischemia-reperfusion. Exp. Ther. Med. 14, 2839–2844 (2017). (PMID: 28912846558588210.3892/etm.2017.4881)
Li, N. & Cheng, C. Y. Mammalian target of rapamycin complex (mTOR) pathway modulates blood–testis barrier (BTB) function through F-actin organization and gap junction. Histol. Histopathol. 31, 961 (2016). (PMID: 269570884938759)
Xue, J., Gruber, F., Tschachler, E. & Zhao, Y. Crosstalk between oxidative stress, autophagy and apoptosis in hemoporfin photodynamic therapy treated human umbilical vein endothelial cells. Photodiagn. Photodyn. Ther. 33, 102137 (2021). (PMID: 10.1016/j.pdpdt.2020.102137)
Tian, Y. et al. Autophagy induced by ROS aggravates testis oxidative damage in diabetes via breaking the feedforward loop linking p62 and Nrf2. Oxid. Med. Cell. Longev. 2020, 1–9 (2020).
Kim, N. et al. Docosahexaenoic acid induces cell death in human non-small cell lung cancer cells by repressing mTOR via AMPK activation and PI3K/Akt inhibition. BioMed Res. Int. 2015, 1–14 (2015). (PMID: 10.1155/2015/812949)
Mihaylova, M. M. & Shaw, R. J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 1016–1023 (2011). (PMID: 21892142324940010.1038/ncb2329)
Yu, L. et al. Chronic arsenic exposure induces ferroptosis via enhancing ferritinophagy in chicken livers. Sci. Total Environ. 890, 164172. https://doi.org/10.1016/j.scitotenv.2023.164172 (2023). (PMID: 10.1016/j.scitotenv.2023.16417237201840)
Valenzuela, R. et al. Molecular adaptations underlying the beneficial effects of hydroxytyrosol in the pathogenic alterations induced by a high-fat diet in mouse liver: PPAR-α and Nrf2 activation, and NF-κB down-regulation. Food Funct. 8, 1526–1537 (2017). (PMID: 2838661610.1039/C7FO00090A)
Liu, B. et al. Protective effects of dietary luteolin against mercuric chloride-induced lung injury in mice: Involvement of AKT/Nrf2 and NF-κB pathways. Food Chem. Toxicol. 113, 296–302 (2018). (PMID: 2942164610.1016/j.fct.2018.02.003)
Liu, B. et al. Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation. J. Nutr. Biochem. 52, 115–123 (2018). (PMID: 2917566810.1016/j.jnutbio.2017.09.025)
Han, B. et al. Dietary melatonin attenuates chromium-induced lung injury via activating the Sirt1/Pgc-1α/Nrf2 pathway. Food Funct. 10, 5555–5565 (2019). (PMID: 3142945810.1039/C9FO01152H)
Indo, H. P. et al. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion 7, 106–118 (2007). (PMID: 1730740010.1016/j.mito.2006.11.026)
المشرفين على المادة: EC 2.7.11.31 (AMP-Activated Protein Kinases)
3T8H1794QW (Eugenol)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
20R035KLCI (Acrylamide)
0 (Amino Acids)
0 (Antifibrinolytic Agents)
EC 2.7.1.1 (mTOR protein, rat)
تواريخ الأحداث: Date Created: 20240122 Date Completed: 20240124 Latest Revision: 20240126
رمز التحديث: 20240127
مُعرف محوري في PubMed: PMC10803763
DOI: 10.1038/s41598-024-52259-1
PMID: 38253778
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-52259-1