Testicular Toxicity following Subacute Exposure of Arsenic and Mancozeb alone and in Combination: Ameliorative Efficacy of Quercetin and Catechin

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  • Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN
  • Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN
  • Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN
  • Division of Veterinary Pathology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN
  • Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN
  • Division of Animal Reproduction and Gynaecology, Faculty of Veterinary Science and Animal Husbandry, R. S. Pura - 181102, Jammu and Kashmir ,IN




Arsenic, Catechin, Mancozeb, Quercetin, Testicular Damage


Mancozeb (MZ) is a contact fungicide having low toxicity in non-target species, but its continuous exposure can be harmful. The aim of the present study was to determine the impact of the toxic interaction between MZ and arsenic on the testicular tissue of rats and to compare the amelioration potential of quercetin and catechin against the induced toxicity. Sixty adult rats were randomly allocated into 10 groups with 6 animals in each. A significant (p<0.05) decline in TAS, TTH, SOD, CAT, GPx, GR and TTH and a rise (p<0.05) in MDA and AOPP-were recorded in testicular tissue of MZ-treated rats in comparison to control. Exposure to different doses of arsenic (10, 50, 100 ppb) also produced a dose-dependent effect on these oxidative biomarkers. Arsenic exposure produces potentiating MZ-induced testicular toxicity in Wistar rats. Testicular damage was further corroborated by extremely severe histopathological changes viz., interstitial as well as sub-capsular congestion, oedema aside from degeneration, necrosis and loss of seminiferous tubules and a drastic deterioration in sperm motility in this group. In contrast, administration of toxicants along with quercetin or catechin markedly attenuated the alterations in oxidative as well as cellular damage biomarkers and testicular histopathological alterations. Our results suggested that simultaneous low dose exposure to arsenic potentiated testicular toxicity induced by MZ. Furthermore, catechin was more potent as compared to quercetin in ameliorating testicular changes induced by concurrent arsenic and MZ exposure.


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Yousuf, R., Verma, P. K., Sharma, P., Sood, S., Pankaj, N. K., & Agarwal, S. (2023). Testicular Toxicity following Subacute Exposure of Arsenic and Mancozeb alone and in Combination: Ameliorative Efficacy of Quercetin and Catechin. Toxicology International, 30(3), 255–267. https://doi.org/10.18311/ti/2023/v30i3/32276
Received 2023-01-01
Accepted 2023-06-30
Published 2023-09-20



Zubrod JP, Bundschuh M, Arts G, Brühl CA, Imfeld G, Knäbel A, Payraudeau S, Rasmussen JJ, Rohr J, Scharmüller A, Smalling K, Stehle S, Schulz R, Schäfer RB. Fungicides: An overlooked pesticide class? Environ Sci Technol. 2019; 53(7):3347-65. https://doi.org/10.1021/acs.est.8b04392 PMid:30835448 PMCid:PMC6536136. DOI: https://doi.org/10.1021/acs.est.8b04392

Goswami SK, Singh V, Chakdar H, Choudhary P. Harmful effects of fungicides-current status. Int J Agri Envirn Biotech. 2018; 11:1025-33.

Belpoggi F, Soffritti M, Guarino M, Lambertini L, Cevolani D, Maltoni C. Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (Mancozeb) in rats. Ann N Y Acad Sci. 2002; 982:123-36. https://doi.org/10.1111/j.1749-6632.2002.tb04928.x PMid:12562632. DOI: https://doi.org/10.1111/j.1749-6632.2002.tb04928.x

Pavlovic V, Cekic S, Kamenov B, Ciric M, Krtinic D. The effect of ascorbic acid on mancozeb-induced toxicity in rat thymocytes. Folia Biologica. 2015; 61(3):116-23.

Edward IR, Ferry DG, Temple WA, Kamrin, MA. Thiodithiocarbamates. In: Pesticide profiles: Toxicity, environmental impact, and fate. New York: CRC Lewis Publishers; 1997. p. 91-132.

Runkle J, Flocks J, Economos J, Dunlop AL. A systematic review of Mancozeb as a reproductive and developmental hazard. Environ Int. 2017; 99:29-42. https://doi. org/10.1016/j.envint.2016.11.006 PMid:27887783. DOI: https://doi.org/10.1016/j.envint.2016.11.006

Mahadevaswami MP, Jadaramkunti UC, Hiremath MB, Kaliwal BB. Effect of mancozeb on ovarian compensatory hypertrophy and biochemical constituents in hemicastrated albino rat. Reprod Toxicol. 2000; 14(2):127-34. https://doi. org/10.1016/S0890-6238(00)00064-2 PMid:10825676. DOI: https://doi.org/10.1016/S0890-6238(00)00064-2

Baligar PN, Kaliwal BB. Induction of gonadal toxicity to female rats after chronic exposure to mancozeb. Ind Health. 2001; 39(3):235-43. https://doi.org/10.2486/ indhealth.39.235 PMid:11499999. DOI: https://doi.org/10.2486/indhealth.39.235

Rossi G, Buccione R, Baldassarre M, Macchiarelli G, Palmerini MG, Cecconi S. Mancozeb exposure in vivo impairs mouse oocyte fertilizability. Reprod Toxicol. 2006; 21(2):216-9. https://doi.org/10.1016/j.reprotox.2005.08.004 PMid:16213123. DOI: https://doi.org/10.1016/j.reprotox.2005.08.004

Ksheersagar RL, Kaliwal BB. Temporal effects of mancozeb on testes, accessory reproductive organs and biochemical constituents in albino mice. Environ Toxicol Pharmacol. 2003; 15:9-17. https://doi.org/10.1016/j.etap.2003.08.006 PMid:21782674. DOI: https://doi.org/10.1016/j.etap.2003.08.006

Joshi SC, Gulati N, Gajraj A. Evaluation of toxic impacts of mancozeb on testis in rats. Asian J Exp Sci. 2005; 19(1):73- 83.

Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M. Arsenic: Toxicity, oxidative stress and human disease. J Appl Toxicol. 2011; 31(2):95-107. https://doi.org/10.1002/jat.1649 PMid:21321970. DOI: https://doi.org/10.1002/jat.1649

Singh AP, Goel RK, Kaur T. Mechanisms pertaining to arsenic toxicity. Toxicol Int. 2011; 18(2):87-93. https://doi. org/10.4103/0971-6580.84258 PMid:21976811 PMCid: PMC3183630. DOI: https://doi.org/10.4103/0971-6580.84258

Sodhi KK, Kumar M, Agrawal PK, Singh DK. Perspectives on arsenic toxicity, carcinogenicity and its systemic remediation strategies. Environ Tech Innovation. 2019; 16:100462. https://doi.org/10.1016/j.eti.2019.100462. DOI: https://doi.org/10.1016/j.eti.2019.100462

Ratnaike RN. Acute and chronic arsenic toxicity. Postgraduate Med J. 2003; 79(933):391-96. https://doi. org/10.1136/pmj.79.933.391 PMid:12897217 PMCid: PMC1742758. DOI: https://doi.org/10.1136/pmj.79.933.391

Baltaci BB, Uygur R, Caglar V, Aktas C, Aydin M, Ozen OA. Protective effects of quercetin against arsenic‐induced testicular damage in rats. Andrologia. 2016; 48(10):1202- 13. https://doi.org/10.1111/and.12561 PMid:26992476. DOI: https://doi.org/10.1111/and.12561

Zeng Q, Yi H, Huang L, An Q, Wang H. Long-term arsenite exposure induces testicular toxicity by redox imbalance, G2/M cell arrest and apoptosis in mice. Toxicol. 2019; 411:122-32. https://doi.org/10.1016/j.tox.2018.09.010 PMid:30278210. DOI: https://doi.org/10.1016/j.tox.2018.09.010

Erkan M, Aydin Y, Yilmaz BO, Yildizbayrak N. Arsenicinduced oxidative stress in reproductive systems. Toxicol. 2021; 145-155. https://doi.org/10.1016/B978-0-12-819092- 0.00016-9. DOI: https://doi.org/10.1016/B978-0-12-819092-0.00016-9

Mahajan L, Verma PK, Raina R, Sood S. Potentiating effect of imidacloprid on arsenic-induced testicular toxicity in Wistar rats. BMC Pharmacol Toxicol. 2018; 19:48. https://doi.org/10.1186/s40360-018-0239-9 PMid: 30064523 PMCid: PMC6069554. DOI: https://doi.org/10.1186/s40360-018-0239-9

Kayode AO, Abimbola A, Adesola AF, Teslim FD, Dorcas WA. Catechin attenuates the effect of combined arsenic and deltamethrin toxicity by abrogation of oxidative stress and inflammation in Wistar rats. Adv Biochem. 2019; 7(2):51. https://doi.org/10.11648/j.ab.20190702.12. DOI: https://doi.org/10.11648/j.ab.20190702.12

Lovaković BT. Cadmium, arsenic, and lead: Elements affecting male reproductive health. Curr Opin Toxicol. 2020; 19:7-14. https://doi.org/10.1016/j.cotox.2019.09.005. DOI: https://doi.org/10.1016/j.cotox.2019.09.005

Liu P, Li R, Tian X, Zhao Y, Li M, Wang M, Yan X. Co-exposure to fluoride and arsenic disrupts intestinal flora balance and induces testicular autophagy in offspring rats. Ecotoxicol Environ Safety. 2021; 222:112506. https:// doi.org/10.1016/j.ecoenv.2021.112506 PMid:34265531. DOI: https://doi.org/10.1016/j.ecoenv.2021.112506

Ramos-Treviño J, Bassol-Mayagoitia S, Hernández-Ibarra JA, Ruiz-Flores P, Nava-Hernández MP. Toxic effect of cadmium, lead, and arsenic on the sertoli Cell: Mechanisms of damage involved. DNA Cell Biol. 2018; 37(7):600-8. https://doi.org/10.1089/dna.2017.4081 PMid:29746152. DOI: https://doi.org/10.1089/dna.2017.4081

Wu S, Zhong G, Wan F, Jiang X, Tang Z, Hu T, Rao G, Lan J, Hussain R, Tang L, Zhang H, Huang R, Hu L. Evaluation of toxic effects induced by arsenic trioxide or/and antimony on autophagy and apoptosis in testis of adult mice. Environ Sci Pollut Res Int. 2021; 28(39):54647-60. https://doi. org/10.1007/s11356-021-14486-1 PMid:34014480. DOI: https://doi.org/10.1007/s11356-021-14486-1

Gullino ML, Tinivella F, Garibaldi A, Kemmitt GM, Bacci L, Sheppard B. Mancozeb past, present and future. Plant Dis. 2010; 94(9):1076-86. https://doi.org/10.1094/PDIS-94- 9-1076 PMid:30743728. DOI: https://doi.org/10.1094/PDIS-94-9-1076

Iorio R, Castellucci A, Rossi G, Cinque B, Cifone MG, Macchiarelli G, Cecconi S. Mancozeb affects mitochondrial activity, redox status, and ATP production in mouse granulosa cells. Toxicol In Vitro. 2015; 30(1PtB):438-45. https://doi.org/10.1016/j.tiv.2015.09.018 PMid:26407525. DOI: https://doi.org/10.1016/j.tiv.2015.09.018

Girish BP, Reddy PS. Forskolin ameliorates mancozebinduced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis. J Biochem Mol Toxicol. 2018; 32(2). https://doi.org/10.1002/jbt.22026 PMid:29283200. DOI: https://doi.org/10.1002/jbt.22026

Kwon D, Chung HK, Shin WS, Park YS, Kwon SC, Song JS, Park BG. Toxicological evaluation of dithiocarbamate fungicide mancozeb on the endocrine functions in male rats. Mol Cell Toxicol. 2018; 14(1):105-12. https://doi. org/10.1007/s13273-018-0013-5. DOI: https://doi.org/10.1007/s13273-018-0013-5

Mehrzadi S, Bahrami N, Mehrabani M, Motevalian M, Mansouri E, Goudarzi M. Ellagic acid: A promising protective remedy against testicular toxicity induced by arsenic. Biomed Pharmacother. 2018; 103:1464-72. https:// doi.org/10.1016/j.biopha.2018.04.194 PMid:29864931. DOI: https://doi.org/10.1016/j.biopha.2018.04.194

Zhang M, Swarts SG, Yin L, Liu C, Tian Y, Cao Y, Swarts M, Yang S, Zhang SB, Zhang K, Ju S, Olek DJ Jr, Schwartz L, Keng PC, Howell R, Zhang L, Okunieff P. Antioxidant properties of quercetin. Adv Exp Med Biol. 2011; 701:283-9. https:// doi.org/10.1007/978-1-4419-7756-4_38 PMid:21445799. DOI: https://doi.org/10.1007/978-1-4419-7756-4_38

Nirankari S, Kamal R, Dhawan DK. Neuroprotective role of quercetin against arsenic induced oxidative stress in rat brain. Environ Analyt Toxicol. 2016; 6(2):359-64. https:// doi.org/10.4172/2161-0525.1000359. DOI: https://doi.org/10.4172/2161-0525.1000359

Wongmekiat O, Peerapanyasut W, Kobroob A. Catechin supplementation prevents kidney damage in rats repeatedly exposed to cadmium through mitochondrial protection. Naunyn-Schmiedebergs Arch Pharmacol. 2018; 391(4):385-94. https://doi.org/10.1007/s00210-018-1468-6 PMid:29356841. DOI: https://doi.org/10.1007/s00210-018-1468-6

Manach C, Texier O, Morand C, Crespy V, Régérat F, Demigné C, Rémésy C. Comparison of the bioavailability of quercetin and catechin in rats. Free Radic Biol Med. 1999; 27(11-12):1259-66. https://doi.org/10.1016/S0891- 5849(99)00159-8 PMid:10641719. DOI: https://doi.org/10.1016/S0891-5849(99)00159-8

Bharrhan S, Koul A, Chopra K, Rishi P. Catechin suppresses an array of signaling molecules and modulates alcoholinduced endotoxin mediated liver injury in a rat model. PLoS ONE. 2011; 6(6):e20635. https://doi.org/10.1371/journal. pone.0020635 PMid:21673994 PMCid:PMC3108820. DOI: https://doi.org/10.1371/journal.pone.0020635

Chen XQ, Hu T, Han Y, Huang W, Yuan HB, Zhang YT, Du Y, Jiang YW. Preventive effects of catechins on cardiovascular disease. Molecules. 2016; 21(12):1759. https://doi.org/ 10.3390/molecules21121759 PMid:28009849 PMCid: PMC6273873. DOI: https://doi.org/10.3390/molecules21121759

Coșarcă S, Tanase C, Muntean DL. Therapeutic aspects of catechin and its derivatives- An update. Acta Biologica Marisiensis. 2019; 2(1):21-9. https://doi.org/10.2478/abmj- 2019-0003. DOI: https://doi.org/10.2478/abmj-2019-0003

Grzesik M, Naparło K, Bartosz G, Sadowska-Bartosz I. Antioxidant properties of catechins: Comparison with other antioxidants. Food Chem. 2018; 241:480-92. https:// doi.org/10.1016/j.foodchem.2017.08.117 PMid:28958556. DOI: https://doi.org/10.1016/j.foodchem.2017.08.117

Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999; 26(9-10):1231-7. https://doi.org/10.1016/ S0891-5849(98)00315-3 PMid:10381194. DOI: https://doi.org/10.1016/S0891-5849(98)00315-3

Motchnik PA, Frei B, Ames BN. Measurement of antioxidants in human blood plasma. Meth Enzymol. 1994; 234:269-79. https://doi.org/10.1016/0076-6879(94)34094-3 PMid:7808294. DOI: https://doi.org/10.1016/0076-6879(94)34094-3

Aebi HE. Catalase, In: Bergmeyer HU, eds. Methods of enzymatic analysis. New York: Academic Press; 1983. p. 276-286.

Hafeman DG, Sunde RA, Hoekstra WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr. 1974; 104(5):580-7. https://doi.org/10.1093/ jn/104.5.580 PMid:4823943. DOI: https://doi.org/10.1093/jn/104.5.580

Marklund S, Marklund G. Involvement of the superoxide anion radical in autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974; 47:469- 74. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x PMid:4215654. DOI: https://doi.org/10.1111/j.1432-1033.1974.tb03714.x

Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975; 250(14):5475-80. https://doi.org/10.1016/ S0021-9258(19)41206-4 PMid:237922. DOI: https://doi.org/10.1016/S0021-9258(19)41206-4

Rehman SU. Lead-induced regional lipid peroxidation in brain. Toxicol Lett. 1984; 21(3):333-7. https://doi. org/10.1016/0378-4274(84)90093-6 PMid: 6740722. DOI: https://doi.org/10.1016/0378-4274(84)90093-6

Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49(5):1304-13. https://doi.org/10.1038/ki.1996.186 PMid:8731095. DOI: https://doi.org/10.1038/ki.1996.186

Domico LM, Cooper KR, Bernard LP, Zeevalk GD. Reactive Oxygen Species generation by the Ethylene- Bis-Dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells. Neurotoxicology. 2007; 28(6):1079-91. https://doi. org/10.1016/j.neuro.2007.04.008 PMid:17597214 PMCid: PMC2141682. DOI: https://doi.org/10.1016/j.neuro.2007.04.008

Srivastava AK, Ali W, Singh R, Bhui K, Tyagi S, Al-Khedhairy AA, Srivastava PK, Musarrat J, Shukla Y. Mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes. Life Sci. 2012; 90(21-22):815-24. https://doi.org/10.1016/j.lfs.2011.12.013 PMid:22289270. DOI: https://doi.org/10.1016/j.lfs.2011.12.013

Calviello G, Piccioni E, Boninsegna A, Tedesco B, Maggiano N, Serini S, Wolf FI, Palozza P. DNA damage and apoptosis induction by the pesticide mancozeb in rat cells: Involvement of the oxidative mechanism. Toxicol Applied Pharmacol. 2006; 211(2):87-96. https://doi.org/10.1016/j. taap.2005.06.001 PMid: 16005924. DOI: https://doi.org/10.1016/j.taap.2005.06.001

Renu K, Madhyastha H, Madhyastha R, Maruyama M, Vinayagam S, Gopalakrishnan AV. Review on molecular and biochemical insights of arsenic-mediated male reproductive toxicity. Life Sci. 2018; 212:37-58. https://doi. org/10.1016/j.lfs.2018.09.045 PMid:30267786. DOI: https://doi.org/10.1016/j.lfs.2018.09.045

Nava-Rivera LE, Betancourt-Martínez ND, Lozoya- Martínez R, Carranza-Rosales P, Guzmán-Delgado NE, Carranza-Torres IE, Morán-Martínez J. Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure. Sci Reports. 2021; 11(1):1-16. https://doi.org/10.1038/s41598-021-87677-y PMid:33859283 PMCid:PMC8050275. DOI: https://doi.org/10.1038/s41598-021-87677-y

Elsharkawy EE, Abd El-Nasser M, Bakheet AA. Mancozeb impaired male fertility in rabbits with trials of glutathione detoxification. Reg Toxicol Pharmacol. 2019; 105:86-98. https://doi.org/10.1016/j.yrtph.2019.04.012 PMid:31014950. DOI: https://doi.org/10.1016/j.yrtph.2019.04.012

Mahdi H, Tahereh H, Esmaiel S, Massood E. Vitamins E and C prevent apoptosis of testicular and ovarian tissues following mancozeb exposure in the first-generation mouse pups. Toxicol Ind Health. 2019; 35(2):136-44. https://doi. org/10.1177/0748233718818692 PMid:30651039. DOI: https://doi.org/10.1177/0748233718818692

Sharma A, Kshetriyanum C, Patel B, Kashyap R, Sadhu HG, Kumar S. Prevention of arsenic induced testicular oxidative stress and DNA damage by coenzyme Q10 and vitamin E in Swiss Albino mice. J Infertility Reprod Biol. 2021; 9(2):93-9.

Han Y, Liang C, Yu Y, Manthari RK, Cheng C, Tan Y, Li X, Tian X, Fu W, Yang J, Yang W, Xing Y, Wang J, Zhang J. Chronic arsenic exposure lowered sperm motility via impairing ultra-microstructure and key proteins expressions of sperm acrosome and flagellum formation during spermiogenesis in male mice. Sci Total Environ. 2020; 734:139233. https://doi.org/10.1016/j. scitotenv.2020.139233 PMid:32460071. DOI: https://doi.org/10.1016/j.scitotenv.2020.139233

Mohammadi-Sardoo M, Mandegary A, Nabiuni M, Nematollahi-Mahani SN, Amirheidari B. Mancozeb induces testicular dysfunction through oxidative stress and apoptosis: Protective role of N-acetylcysteine antioxidant. Toxicol Ind Health. 2018; 34(11):798-811. https://doi. org/10.1177/0748233718778397 PMid:30037311. DOI: https://doi.org/10.1177/0748233718778397

Concessao P, Bairy LK, Raghavendra AP. Effect of aqueous seed extract of Mucuna pruriens on arsenic-induced testicular toxicity in mice. Asian Pac J Reprod. 2020; 9 (2):77. https://doi.org/10.4103/2305-0500.281077. DOI: https://doi.org/10.4103/2305-0500.281077

Kackar R, Srivastava MK, Raizada RB. Induction of gonadal toxicity to male rats after chronic exposure to mancozeb. Indust Health. 1997; 35(1):104-11. https://doi.org/10.2486/ indhealth.35.104 PMid:9009508. DOI: https://doi.org/10.2486/indhealth.35.104

Izak-Shirian F, Najafi-Asl M, Azami B, Heidarian E, Najafi M, Khaledi M, Nouri A. Quercetin exerts an ameliorative effect in the rat model of diclofenacinduced renal injury through mitigation of inflammatory response and modulation of oxidative stress. Eur J Inflam. 2022; 20:1721727X221086530. https://doi. org/10.1177/1721727X221086530. DOI: https://doi.org/10.1177/1721727X221086530

Arslan AS, Seven I, Mutlu SI, Arkali G, Birben N, Seven PT. Potential ameliorative effect of dietary quercetin against lead-induced oxidative stress, biochemical changes, and apoptosis in laying Japanese quails. Ecotoxicol Environ Saf. 2022; 231:113200. https://doi.org/10.1016/j. ecoenv.2022.113200 PMid:35051762. DOI: https://doi.org/10.1016/j.ecoenv.2022.113200

Akinmoladun AC, Olaniyan OO, Famusiwa CD, Josiah SS, Olaleye MT. Ameliorative effect of quercetin, catechin, and taxifolin on rotenone-induced testicular and splenic weight gain and oxidative stress in rats. J Basic Clin Physiol Pharmacol. 2020; 15(3):31. https://doi.org/10.1515/jbcpp- 2018-0230 PMid:31940286. DOI: https://doi.org/10.1515/jbcpp-2018-0230