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Rhus tripartite methanolic extract alleviates propylparaben-induced reproductive toxicity via anti-inflammatory, antioxidant, 5-α reductase in male rats

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Abstract

Evidence showed that herbal medicine could be beneficial for protection against diseases that may be exist in consequence of exposure to environmental toxicants. Propylparaben (PrP) is used as preservative in food, pharmaceuticals, and cosmetics. It is classified as one of endocrine disruptive chemicals (EDCs). This study evaluated the protective effect of Rhus tripartita methanolic extract (RTME) against reproductive toxicity induced by PrP in male rats. A total of 60 Wister albino rats were divided into four groups (15 rats for each group). Group I (control): rats received the vehicle (DMSO), group II: normal rats received RTME (10 mg/kg/day), group III: rats received PrP (10 mg/kg/day), and group IV: rats received PrP (10 mg/kg/day) and RTME (10 mg/kg/day) for 4 weeks. At the end of experiment, levels of testosterone, dihydrotestosterone (DHT), and 5α-reductase were analyzed in sera. Data obtained showed a significant reduction in the levels of testosterone, dihydrotestosterone (DHT), and 5α- reductase in rats given PrP versus control (p < 0.001) and RTME treatment improved these parameters but not returned to normal. Data obtained showed a significant elevation in levels of IL-6 and TNF-α in the testis of rats given PrP versus control (p < 0.001), these inflammatory mediators were significant reduced in rats treated with RTME compared with untreated rats (p < 0.001). There was a positive correlation between level of DHT and antioxidant enzymes activities (r = 0.56). A significant elevation in the levels of MDA with reduction in the activities of GST, GSPx, SOD, and catalase (p < 0.001) in rat testicular tissues of PrP group versus control (p < 0.001) was found. Treatment with RTME significantly reduced the levels of MDA and enhanced activities of GST, GSPx, SOD, and catalase (p < 0.001) compared to untreated group (p < 0.001). In conclusion, the active ingredient components of RTME abrogate the toxicity of PrP by exhibiting antioxidative and anti-inflammatory effects, enhancing 5-α reductase with improved hormonal status against PrP- induced testicular damage.

Graphical Abstract

Toxicity of propylparaben, and effect of Rhus tripartita methanolic extract

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Data availability

All datasets generated or analyzed during this study are included in the manuscript.

Abbreviations

RTME:

Rhus tripartita methanolic extract

PrP:

propylparaben

DHT:

dihydrotestosterone

MDA:

malondialdehyde

GTS:

glutathione transferase

SOD:

superoxide dismutase

GPXs:

glutathione peroxidase

IL-6:

interlukine-6

TNF-α:

tumor necrosis factor

PBs:

parabens

References

  • Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, Arafa M, Panner Selvam MK, Shah R (2021) Male infertility. Lancet 397:319–333

    Google Scholar 

  • Akram A, Oroojan AA, Heidari H, Ghaedi E, Nooshabadi MRR (2014) Effects of hydro-alcoholic extract of Rhus coriaria (Sumac) seeds on reproductive complications of nicotinamide-streptozotocin induced type-2 diabetes in male mice. World J Mens Health 32(3):151–158

    Google Scholar 

  • Alahmar AT (2019) Role of oxidative stress in male infertility: an updated review. J Hum Reprod Sci 12(1):4–18

    CAS  Google Scholar 

  • Amory JK, Bremner WJ (2003) Regulation of testicular function in men: implications for male hormonal contraceptive development. J Steroid Biochem Mol Biol 85:357–361

    CAS  Google Scholar 

  • Anderson MT, Staal F, Gitler C, Herzenberg LA (1994) Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. Proc Natl Acad Sci 91:11527–11531

    CAS  Google Scholar 

  • Ates PS, Unal I, Ustundag UV, Alturfan AA, Yigitbasi T, Emekli-Alturfan E (2018) Methylparaben induces malformations and alterations on apoptosis, oxidant-antioxidant status, ccnd1 and myca expressions in zebrafish embryos. J Biochem Mol Toxicol 32(3):e22036

    Google Scholar 

  • Alimi H, Mbarki S, Barka ZB, Feriani A, Bouoni Z, Hfaeidh N et al (2013) Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark extract against ethanol-induced ulcer in rats. Gen Physiol Biophys 32:115e27

    Google Scholar 

  • Brand W, Boon PE, Hessel EVS, Meesters JAJ, Weda M, Schuur AG (2017) Exposure to and toxicity of methyl-, ethyl- and propylparaben: a literature review with a focus on endocrine-disrupting properties. RIVM Rep 28:1–109

    Google Scholar 

  • Bräuner EV, Uldbjerg CS, Lim YH, Gregersen LS, Krause M, Frederiksen H, Andersson AM (2022) Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid. Environ Int 158:106987

    Google Scholar 

  • Błedzka D, Gromadzi´nska J, Wasowicz W (2014) Parabens. From environmental studies to human health. Environ Int 67:27–42

    Google Scholar 

  • Bodin L, Rogiers V, Bernauer U, Chaudhry Q, Coenraads PJ, Dusinska M, Ezendam J, Galli C L GE, Granum B et al (2021) Opinion of the Scientific Committee on Consumer safety (SCCS)—Final opinion on propylparaben. Regul Toxicol Pharmacol 125:105005

    Google Scholar 

  • Baker BH, Wu H, Laue HE, Boivin A, Gillet V, Langlois MF, Bellenger JP, Baccarelli AA, Takser L (2020) Methylparaben in meconium and risk of maternal thyroid dysfunction, adverse birth outcomes, and attention-deficit hyperactivity disorder (ADHD). Environ Int 139:105716

    CAS  Google Scholar 

  • Ben Barka Z et al (2016a) Protective effects of edible Rhus tripartita (Ucria) stem extract against ethanol-induced gastric ulcer in rats. J Funct Foods 30:260–269

    CAS  Google Scholar 

  • Ben Barka Z et al (2016b) Evaluation of the anti-diarrheal activity of the hydromethanolic root extract of Rhus tripartita (Ucria) (Anacardiaceae). Biomed Pharmacother Biomed Pharmacother 83:827–834

    Google Scholar 

  • Bereketoglu C, Pradhan A (2019) Comparative transcriptional analysis of methylparaben and propylparaben in zebrafish. Sci Total Environ 671:129–139

    CAS  Google Scholar 

  • Borochov-Neori H, Lazarovitch N, Judeinstein S, Patil BS, Holland D (2013) Climate and salinity effects on color and health promoting properties in the pomegranate (punica granatum l.) fruit arils. ACS Symp Ser 1129:43–61. https://doi.org/10.1021/bk-2013-1129.ch003

    Article  CAS  Google Scholar 

  • Brown SE, Sant KE, Fleischman SM, Venezia O, Roy MA, Zhao L, Timme- Laragy AR (2018) Pancreatic beta cells are a sensitive target of embryonic exposure to butylparaben in zebrafish (Danio rerio). Birth Defects Res 110:933–948

    CAS  Google Scholar 

  • Cotran RS (1999) Acute and chronic inflammation. Robbins Pathological Basis of Disease; Elsevier Health Sciences. PA, USA, Philadelphia, pp 50–88

    Google Scholar 

  • Darbre PD, Harvey PW (2008) Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks. J Appl Toxicol 28:561–578

    CAS  Google Scholar 

  • Darbre PD (2017) Endocrine disruptors and obesity. Curr Obes Rep 6:18–27

    Google Scholar 

  • Dewalque L, Pirard C, Charlier C (2014) Measurement of urinary biomarkers of parabens, benzophenone-3, and phthalates in a Belgian population. Biomed Res Int 2014:1–13, 649314

  • Dutta S, Sengupta P, Slama P, Roychoudhury S (2021) Oxidative stress, testicular inflammatory pathways, and male reproduction. Int J Mol Sci 22(18):10043

    CAS  Google Scholar 

  • El-Mokasabi F (2014) The state of the art of traditional herbal medicine in the eastern Mediterranean coastal region of Libya. Middle East J Sci Res 21:575e82

    Google Scholar 

  • Flohé L, Brigelius-Flohé R, Saliou C, Traber MG, Packer L (1997) Redox regulation of NF-kappa B activation. Free Radic Biol Med 22:1115–1126

    Google Scholar 

  • Gazin V, Marsden E, Marguerite F (2013) Oral propylparaben administration to juvenile male wistar rats did not induce toxicity in reproductive organs. Toxicol Sci 136(2):392–401

    CAS  Google Scholar 

  • Hines EP, Mendola P, von Ehrenstein OS, Ye X, Calafat AM, Fenton SE (2015) Concentrations of environmental phenols and parabens in milk, urine and serum of lactating North Carolina women. Reprod Toxicol 54:120–128

    CAS  Google Scholar 

  • Hegazy HG, Ali EH, Elgoly AH (2015) Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model. Cytokine 71:173–180

    CAS  Google Scholar 

  • Hajizadeh Y, Feizabadi GK, Feizi A (2020) Dietary habits and personal care product use as predictors of urinary concentrations of parabens in Iranian adolescents. Environ Toxicol Chem 39:2378–2388

    CAS  Google Scholar 

  • Haman C, Dauchy X, Rosin C, Munoz J-F (2015) Occurrence, fate and behavior of parabens in aquatic environments: A review. Water Res 68:1–11

    CAS  Google Scholar 

  • Imen A, Criad P, Salmieri S, Najjaa H, Isoda H, Neffati M, Lacroix M (2019) Edible Rhus tripartita fruit as source of health-promoting compounds: characterization of bioactive components and antioxidant properties. Eur Food Res Technol 245:2641–2654

    CAS  Google Scholar 

  • Jeong PS, Lee S, Park SH, Kim MJ, Kang HG, Nanjidsuren T, Son HC, Song BS, Koo DB, Sim BW, Kim SU (2020) Butylparaben is toxic to porcine oocyte maturation and subsequent embryonic development following in vitro fertilization. Int J Mol Sci 21:3692

    CAS  Google Scholar 

  • Kang S, Kim S, Park J, Kim H-J, Lee J, Choi G, Choi S, Kim S, Kim SY, Moon H-B et al (2013) Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers. Sci Total Environ 461–462:214–221

    Google Scholar 

  • Liu W, Zhou Y, Li J, Sun X, Li H, Jiang Y, Peng Y, Zhao H, Xia W, Li Y et al (2019) Parabens exposure in early pregnancy and gestational diabetes mellitus. Environ Int 126:468–475

    CAS  Google Scholar 

  • Linder RE, Strader LF, Rehnberg GL (1990) Effect of acute exposure to boric acid on the male reproductive system of the rat. J Toxicol Environ Health 31(2):133–146

    CAS  Google Scholar 

  • Mahjoub MA, Ammar S, Mighri Z (2005) A new biflavonoid and an isobiflavonoid from Rhus tripartitum. Nat Prod Res 9:723e9

    Google Scholar 

  • Meng F, Jiao XF, Chen F, Zhang XY, Duan ZQ, Ding ZM, Wu D, Wang YS, Zhang SX, Miao YL, Huo LJ (2020) Isobutylparaben negatively affects porcine oocyte maturation through increasing oxidative stress and cytoskeletal abnormalities. Environ Mol Mutagen 61:433–444

    CAS  Google Scholar 

  • Mohammed AEI (2015) Phytoconstituents and the study of antioxidant, antimalarial and antimicrobial activities of Rhus tripartite growing in Egypt. J Pharmacogn Phytochem 4:2762–2781

    Google Scholar 

  • Nowak K, Ratajczak-Wrona W, G´orska M, Jabło´nska E (2018) Parabens and their effects on the endocrine system. Mol Cell Endocrinol 474:238–251

    CAS  Google Scholar 

  • Oluwafemi OA, Nwafor-Ezeh PI, Rotimi DE, Iyobhebhe M, Ogunlakin AD, Ojo AB (2023) Apoptosis, inflammation, and oxidative stress in infertility: a mini review. Toxicology Reports 10:448–462

    CAS  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1):158–169

    CAS  Google Scholar 

  • Pedersen KL, Pedersen SN, Christiansen LB, Korsgaard B, Bjerregaard P (2000) The preservatives ethyl-, propyl- and butylparaben are oestrogenic in an in vivo fish assay. Pharmacol Toxicol 86:110–113

    CAS  Google Scholar 

  • Rayne S, Mazza G (2007) Biological activities of extracts from sumac (Rhus spp.): a review. Plant Foods Hum Nutr 62:165–175

    Google Scholar 

  • Roshankhah S, Gholami MR, Salahshoor MR (2020) Evaluation of male infertility treatment following Rhus coriaria extract administration on rats exposed to morphine. Mol Biol Rep. 47:6073–6081

    CAS  Google Scholar 

  • Sahreen S, Khan MR, Khan RA, Shah NA (2013) Effect of Carissa opaca leaves extract on lipid peroxidation, antioxidant activity and reproductive hormones in male rats. Lipids Health Dis 12:90

    Google Scholar 

  • Schilit SL, Menon S, Friedrich C, Kammin T, Wilch E, Hanscom C, Jiang S, Kliesch S, Talkowski ME, Tüttelmann F, MacQueen AJ (2020) SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility. J Hum Genet 106(1):41–57. https://doi.org/10.1016/j.ajhg

    Article  CAS  Google Scholar 

  • Schreibe E, Garcia T, Sharma RP, Torrente M, Domingo JL, Gomez M (2019) Oxidative stress in testes of rats exposed to n-butylparaben. Food Chem Toxicol 131:110573

    Google Scholar 

  • Shahat AA, Alsaid MS, Rafatullah S, Al-Sohaibani MO, Parvez MK, Mohammed S, Al-Dosaril MS, Exarchou V, Pieters L (2016b) Treatment with Rhus tripartita extract curtails isoproterenol-elicited cardiotoxicity and oxidative stress in rats. BMC Complement Altern Med 16:351

    Google Scholar 

  • Shahat AA, Ibrahim AY, Al-Ghamdi AAM, Alsaid MS (2016a) Phytochemical investigation of Rhus tripartita and its activity against cyclooxygenases and acetylcholinesterase. Trop J Pharm Res 15(8):1697–1706

    CAS  Google Scholar 

  • Shekhar S, Sood S, Showkat S, Lite C, Chandrasekhar A, Vairamani M, Barathi S, Santosh W (2017) Detection of phenolic endocrine disrupting chemicals (EDCs) from maternal blood plasma and amniotic fluid in Indian population. Gen Comp Endocrinol 241:100–107

    CAS  Google Scholar 

  • Soni MG, Carabin IG, Burdock GA (2005) Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol 43:985

    CAS  Google Scholar 

  • Tlili N, Tir M, Benlajnef H, Khemir C, Mejri H, Rejeb S et al (2014a) Variation in protein and oil content and fatty acid composition of Rhus tripartitum fruits collected at different maturity stages in different locations. Ind. Crops Prod 50:197–201

    Google Scholar 

  • Tlili N, Mejri H, Ahia Y, Saadaoui E, Rejeb S, Khaldi A et al (2014b) Phytochemicals and antioxidant activities of Rhus tripartitum (Ucria) fruits depending on locality and different stages of maturity. Food Chem 160:98–103

    CAS  Google Scholar 

  • Tlili N et al (2016) Effects of Rhus tripartitum fruit extract on CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 94:801–807

    CAS  Google Scholar 

  • Titi-Lartey OA, Khan YS (2022) Embryology, testicle. Stat Pearls Publishing, Treasure Island (FL) Available at: http://www.ncbi.nlm.nih.gov/books/NBK557763/. Accessed Apr 2022

    Google Scholar 

  • Tanaka T, Kanatsu-Shinohara M, Lei Z, Rao CV, Shinohara T (2016) The luteinizing hormone-testosterone pathway regulates mouse spermatogonial stem cell self-renewal by suppressing WNT5A expression in sertoli cells. Stem Cell Rep 7:279–291

    CAS  Google Scholar 

  • Walker M H & Tobler K J, Female Infertility (2020). PubMed; Stat Pearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK556033/. Accessed Apr 2022

  • Wei F, Mortimer M, Cheng H, Sang N, Guo LH (2021) Parabens as chemicals of emerging concern in the environment and humans: a review. Sci. Total Environ 778:146150

    CAS  Google Scholar 

  • Wiwat R, Toppari J, Virtanen HE (2023) Environmental toxicants and male fertility. Best Pract Res Clin Obstet Gynaecol 86:102298

    Google Scholar 

  • World Health Organization (2020) Infertility. https://www.who.int/news-room/fact-sheets/detail/infertility. Accessed Apr 2022

  • Yang C, Lim W, Bazer FW, Song G (2018) Butyl paraben promotes apoptosis in human trophoblast cells through increased oxidative stress-induced endoplasmic reticulum stress. Environ Toxicol 33:436–445

    CAS  Google Scholar 

  • Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Vanderpoel S (2009) International committee for monitoring assisted reproductive technology and the world health organization revised glossary of ART terminology. Fertil Steril 92:1520–152

    CAS  Google Scholar 

  • Zhang H, Quan Q, Li X, Sun W, Zhu K, Wang X, Sun X, Zhan M, Xu W, Lu L et al (2020) Occurrence of parabens and their metabolites in the paired urine and blood samples from Chinese university students: Implications on human exposure. Environ Res 183:109288

    CAS  Google Scholar 

  • Zhao H, Zheng Y, Zhu L, Xiang L, Zhou Y, Li J, Fang J, Xu S, Xia W, Cai Z (2020) Paraben exposure related to purine metabolism and other pathways revealed by mass spectrometry-based metabolomics. Environ Sci Technol 54:3447–3454

    CAS  Google Scholar 

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Acknowledgements

The authors acknowledge DSR for technical and financial support.

Funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant no. (IFPIP:207-130-1443).

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia

    Rami M. Mosaoa & Taha A. Kumosani

  2. Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Rami M. Mosaoa, Taha A. Kumosani & Soonham S. Yaghmoor

  3. Production of Bioproducts for Industrial Applications Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

    Taha A. Kumosani & Soonham S. Yaghmoor

  4. Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt

    Shaimaa Rihan & Said S. Moselhy

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  1. Rami M. Mosaoa
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Contributions

TAK and SSM design the experiments. RM and SSY run the practical section. SSM: data analysis and interpretation. All authors share in write and review manuscript.

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Correspondence to Said S. Moselhy.

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The study protocol was approved by the Ethics Committee of King Abdulaziz University, Jeddah, Saudi Arabia. The protocol was done according to the ethical guidelines of the 1975 Declaration of Helsinki.

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Mosaoa, R.M., Kumosani, T.A., Yaghmoor, S.S. et al. Rhus tripartite methanolic extract alleviates propylparaben-induced reproductive toxicity via anti-inflammatory, antioxidant, 5-α reductase in male rats. Environ Sci Pollut Res 30, 76969–76976 (2023). https://doi.org/10.1007/s11356-023-27802-8

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