Skip to main content

Advertisement

Log in

The effect of Zataria multiflora on inflammatory cytokine and respiratory symptoms in veterans exposed to sulfur mustard

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

The effect of Zataria multiflora (Z. multiflora) on serum cytokine, chemokines, and respiratory symptoms in the veterans exposed to sulfur mustard (SM) more than two decades (27–30 years) ago was conducted in 2018. Thirty-four patients were randomly assigned to the placebo group (P, mean age (54.40 ± 5.51)) and two treated groups with Z. multiflora extract 5 and 10 mg/kg/day (Z5 and 10; mean age, 58.50 ± 3.60 and 55.18 ± 4.11, respectively). Serum levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), forced expiratory volume-one second (FEV1), and respiratory symptoms including chest wheeze (CW), night wheeze (NW), night cough (NC), and cough and wheeze during exercise (ECW) were assessed at the baseline (phase 0), 1 and 2 months after starting treatment (phase I and II, respectively). The value of FEV1 was significantly increased in Z10 in phase I and II compared with that in phase 0 (p < 0.01 for both) and in Z5 in phase II compared with phase I and 0 (p < 0.001for both). All respiratory symptoms significantly decreased in Z5 and 10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). Serum levels of TNF-α and VEGF were decreased in Z5 and 10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). Serum levels of MCP-1 and EGF were decreased in Z10 in phase I and II compared with those in phase 0 (p < 0.05 to p < 0.001). The percent change of respiratory symptoms, serum levels of cytokines during the treatment period, was significantly improved in the treated groups compared with that in the placebo group. Two months’ of treatment with Z. multiflora improved cytokine levels, respiratory symptom, and FEV1 values in SM-exposed patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abtahi H, Peiman S, Foroumandi M, Safavi E (2016) Long term follow-up of sulfur mustard related bronchiolitis obliterans treatment. Acta Medica Iranica 54(9):605–609

    Google Scholar 

  • Afzali H, Darabi M, Kashanian M (2003) The effect of Zataria multiflora and Foeniculum vulgare in acute cough. Proceeding of the 16th Iran Cong Physiol Pharmacol:19

  • Alavinezhad A, Hedayati M, Boskabady MH (2017) The effect of Zataria multiflora and carvacrol on wheezing, FEV1 and plasma levels of nitrite in asthmatic patients. Avicenna J Phytomed 7(6):531–541

    CAS  Google Scholar 

  • Alavinezhad A, Khazdair MR, Boskabady MH (2018) Possible therapeutic effect of carvacrol on asthmatic patients: a randomized, double blind, placebo-controlled, phase II clinical trial. Phytother Res 32(1):151–159

    Article  CAS  Google Scholar 

  • Amirghofran Z, Ahmadi H, Karimi MH (2012) Immunomodulatory activity of the water extract of Thymus vulgaris, Thymus daenensis, and Zataria multiflora on dendritic cells and T cells responses. J Immun Immunochem 33(4):388–402

    Article  CAS  Google Scholar 

  • Avicenna (1985) Al-Qanun fi al Tibb, (the canon of medicine), Persian edition by Sharaf-Kandi, A.R. Book II

  • Baharara J, Ramezani T, Hosseini N, Mousavi M. (2018) Silver nanoparticles synthesized coating with Zataria multiflora leaves extract induced apoptosis in HeLa cells through p53 activation. Iran J Pharm Res 17(2):627–639

  • Balali-Mood M, Hefazi M (2006) Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic clin pharmacol toxicol 99(4):273–282

    Article  CAS  Google Scholar 

  • Boskabady M, Boskabady MH, Zabihi NA, Boskabady M (2015) The effect of chemical warfare on respiratory symptoms, pulmonary function tests and their reversibility 23–25 years after exposure. Toxicol Ind Health 31(1):79–84

    Article  CAS  Google Scholar 

  • Boskabady MH, Attaran D, Shaffei MN (2008) Airway responses to salbutamol after exposure to chemical warfare. Respirology 13(2):288–293

    Article  Google Scholar 

  • Boskabady MH, Farhadi J (2008) The possible prophylactic effect of Nigella sativa seed aqueous extract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial. J Alternat Complement Med 14(9):1137–1144

    Article  Google Scholar 

  • Boskabady MH, Farhang L, Mahmodinia M, Boskabady M, Heydari GR (2012a) Comparison of pulmonary function and respiratory symptoms in water pipe and cigarette smokers. Respirology 17(6):950–956

    Article  Google Scholar 

  • Boskabady MH, Farhang L, Mahmoodinia M, Boskabady M, Heydari GR (2014a) Prevalence of water pipe smoking in the city of Mashhad (north east of Iran) and its effect on respiratory symptoms and pulmonary function tests. Lung India 31(3):237–243

    Article  Google Scholar 

  • Boskabady MH, Gholami Mhtaj L (2014) Effect of the Zataria multiflora on systemic inflammation of experimental animals model of COPD. Biomed Res Int 2014: 802189

  • Boskabady MH, Jafari Z, Pouraboli I, Babazade B, Rahbardar MG (2012b) Anti-cholinergic effect of Zataria multiflora Boiss on guinea pig tracheal chains. Nat Prod Res 26(16):1523–1528

    Article  CAS  Google Scholar 

  • Boskabady MH, Jalali S, Farkhondeh T, Byrami G (2014b) The extract of Zataria multiflora affect tracheal responsiveness, serum levels of NO, nitrite, PLA2, TP and histamine in sensitized Guinea pigs. J Ethnopharmacol 156:301–308

    Article  Google Scholar 

  • Boskabady MH, Kaveh M, Eftekhar N, Nemati A (2011a) Zataria multiflora Boiss and carvacrol affect β2-adrenoceptors of guinea pig trachea. Evid Based Complement Alternat Med 2011:1–9

    Article  Google Scholar 

  • Boskabady MH, Kolahdoz GH (2002) Prevalence of asthma symptoms among the adult population in the city of Mashhad (north-east of Iran). Respirology 7(3):267–272

    Article  Google Scholar 

  • Boskabady MH, Mehrjardi SS, Rezaee A, Rafatpanah H, Jalali S (2013) The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance. J Ethnopharmacol 150(3):1024–1031

    Article  Google Scholar 

  • Boskabady MH, Tabanfar H (2011) Effect of Zataria multiflora Bois L. on histamine (H1) receptor of guinea pig tracheal chains

  • Boskabady MH, Vahedi N, Amery S, Khakzad MR (2011b) The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. J Ethnopharmacol 137(2):1028–1034

    Article  Google Scholar 

  • Car BD, Meloni F, Luisetti M, Semenzato G, Gialdroni-Grassi G, Walz A (1994) Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Res Crit Care Med 149(3):655–659

    Article  CAS  Google Scholar 

  • Clarke R, Lundy FT, McGarvey L (2015) Herbal treatment in asthma and COPD–current evidence. Clin Phytosci 1(1):4

    Article  CAS  Google Scholar 

  • Darchini-Maragheh E, Balali-Mood M (2018) Delayed complications and long-term management of sulfur mustard poisoning: recent advances by Iranian researchers (part I of II). Iran J Med Sci 43(2):103

    Google Scholar 

  • Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci 94(9):4273–4278

    Article  CAS  Google Scholar 

  • Emad A, Emad V (2007a) Elevated levels of MCP-1, MIP-α and MIP-1β in the bronchoalveolar lavage (BAL) fluid of patients with mustard gas-induced pulmonary fibrosis. Toxicology 240(1–2):60–69

    Article  CAS  Google Scholar 

  • Emad A, Emad Y (2007b) Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J Interf Cytokine Res 27(1):38–43

    Article  CAS  Google Scholar 

  • Evison D, Hinsley D, Rice P (2002) Regular review: chemical weapons. BMJ: Br Med J 324(7333):332–335

    Article  CAS  Google Scholar 

  • Ghabili K, Agutter PS, Ghanei M, Ansarin K, Shoja MM (2010) Mustard gas toxicity: the acute and chronic pathological effects. J Appl Toxicol 30(7):627–643

    Article  CAS  Google Scholar 

  • Gharbi S, Khateri S, Soroush MR, Shamsara M, Naeli P, Najafi A, Korsching E, Mowla SJ (2018) MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care. PLoS One 13(3):e0194530

    Article  CAS  Google Scholar 

  • Gholami Mahtaj L, Boskabady M, Mohamadian Roshan N (2015) The effect of Zataria multiflora and its constituent, carvacrol, on tracheal responsiveness and lung pathology in guinea pig model of COPD. Phytother Res 29:730–736

    Article  CAS  Google Scholar 

  • Ghotbi L, Hassan Z (2002) The immunostatus of natural killer cells in people exposed to sulfur mustard. Int Immunopharmacol 2(7):981–985

    Article  CAS  Google Scholar 

  • Gimeno D, Delclos GL, Ferrie JE, de Vogli R, Elovainio M, Marmot MG, Kivimäki M (2011) Association of CRP and IL-6 with lung function in a middle-aged population initially free from self-reported respiratory problems: the Whitehall II study. Eur J Epidemiol 26(2):135–144

    Article  CAS  Google Scholar 

  • González L, Díaz ME, Miquet JG, Sotelo AI, Fernández D, Dominici FP, Bartke A, Turyn D (2010) GH modulates hepatic epidermal growth factor signaling in the mouse. J Endocrinol 204(3):299–309

    Article  CAS  Google Scholar 

  • Hassan ZM, Ebtekar M (2002) Immunological consequence of sulfur mustard exposure. Immunol Lett 83(3):151–152

    Article  CAS  Google Scholar 

  • Hosseinzadeh H, Ramezani M, G-a S (2000) Antinociceptive, anti-inflammatory and acute toxicity effects of Zataria multiflora Boiss extracts in mice and rats. J Ethnopharmacol 73(3):379–385

    Article  CAS  Google Scholar 

  • Jafari Z, Boskabady MH, Pouraboli I, Babazade B (2011) Zataria multiflora Boiss inhibits muscarinic receptors of incubated tracheal smooth muscle with propranolol. Avicenna J Phytomed 1(1):7–13

    Google Scholar 

  • Karami A, Ghanei M, Alaeddini F, Soltanpour MJ (2011) Vascular endothelial growth factor in bronchoalveolar lavage fluid in sulfur mustard exposed lung patients. Oman Med J 26(2):118–121

    Article  Google Scholar 

  • Karbasi-Afshar R, Shahmari A, Madadi M, Poursaleh Z, Saburi A (2013) Coronary angiography findings in lung injured patients with sulfur mustard compared to a control group. Ann Cardiac Anaesth 16(3):188

    Article  Google Scholar 

  • Keatings VM, Collins PD, Scott DM, Barnes PJ (1996) Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Resp Crit Care Med 153(2):530–534

    Article  CAS  Google Scholar 

  • Khateri S, Balali-Mood M, Blain P, Williams F, Jowsey P, Soroush MR, Behravan E, Sadeghi M (2018) DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure. Toxicol Lett 293:67–72

    Article  CAS  Google Scholar 

  • Khazdair M, Alavinezhad A, Boskabady M (2018a) Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: a randomized double-blind clinical trial. J Clin Pharm Ther 43(5):664–674

    Article  CAS  Google Scholar 

  • Khazdair MR, Boskabady MH (2019) Long term effect of sulfur mustard exposure on hematologic and respiratory status, a case control study. Drug Chem Toxicol 42(3):295–299

    Article  CAS  Google Scholar 

  • Khazdair MR, Boskabady MH (2019a) A double-blind, randomized, placebo-controlled clinical trial on the effect of carvacrol on serum cytokine levels and pulmonary function tests in sulfur mustard induced lung injury. Cytokine 113:311–318

    Article  CAS  Google Scholar 

  • Khazdair MR, Boskabady MH (2019b) The effect of carvacrol on inflammatory mediators and respiratory symptoms in veterans exposed to sulfur mustard, a randomized, placebo-controlled trial. Resp Med 150:21–29

    Article  Google Scholar 

  • Khazdair MR, Boskabady MH, Afshari R, Dadpour B, Behforouz A, Javidi M, Abbasnezhad A, Moradi V, Tabatabaie SS (2012) Respiratory symptoms and pulmonary function testes in lead exposed workers. Iran Red Crescent Med J 14(11):737–742

    Article  Google Scholar 

  • Khazdair MR, Boskabady MH, Ghorani V (2015) Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD. Inhal Toxicol 27(14):731–744

    Article  CAS  Google Scholar 

  • Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH (2018) Pharmacological effects of Zataria multiflora Boiss L. and its constituents, focus on their anti-inflammatory, antioxidant and immunomodulatory effects. Fund Clin Pharmacol 32(1):26–50

    Article  CAS  Google Scholar 

  • Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH (2020) Effect of Zataria multiflora on serum cytokine levels and pulmonary function tests in sulfur mustard-induced lung disorders: a randomized double-blind clinical trial. J Ethnopharmacol 248:112325

    Article  CAS  Google Scholar 

  • Khazdair MR, Rajabi O, Balali-Mood M, Beheshti F, Boskabady MH (2018b) The effect of Zataria multiflora on pulmonary function tests, hematological and oxidant/antioxidant parameters in sulfur mustard exposed veterans, a randomized doubled-blind clinical trial. Env Toxicol Pharmacol 58:180–188

    Article  CAS  Google Scholar 

  • Khosravi A, Franco M, Shokri H, Yahyaraeyat R (2007) Evaluation of the effects of Zataria multiflora, Geranium pelargonium, Myrth and Lemonessences on immune system function in experimental animals. J Vet Res 62(4):119–123

    Google Scholar 

  • Kianmehr M, Rezaei A, Boskabady MH (2016) Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice. Iran J Basic Med Sci 19(4):402–410

    Google Scholar 

  • Kianmehr M, Rezaei A, Hosseini M, Khazdair MR, Rezaee R, Askari VR, Boskabady MH (2017) Immunomodulatory effect of characterized extract of Zataria multiflora on Th 1, Th 2 and Th 17 in normal and Th 2 polarization state. Food Chem Toxicol 99:119–127

    Article  CAS  Google Scholar 

  • Layali I, Shahriary A, Rahmani Talatappe N, Tahmasbpour E, Rostami H, Beigi Harchegani A (2018) Sulfur mustard triggers oxidative stress through glutathione depletion and altered expression of glutathione-related enzymes in human airways. Immunopharmacol Immunotoxicol 40(4):290–296

    Article  CAS  Google Scholar 

  • Mirsadraee M, Attaran D, Boskabady M, Towhidi M (2005) Airway hyperresponsiveness to methacholine in chemical warfare victims. Respiration 72(5):523–528

    Article  CAS  Google Scholar 

  • Mishra NC, Grotendorst GR, Langley RJ et al (2012) Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: possible role of Th17 cells in chronic lung pathology. Int Immunopharmacol 13(1):101–108

    Article  CAS  Google Scholar 

  • Molloy RM, Mc Connell RI, Lamont JV, FitzGerald SP (2005) Automation of biochip array technology for quality results. Clin Chem Lab Med 43(12):1303–1313

    Article  CAS  Google Scholar 

  • Mozaffarian V (1996) A dictionary of Iranian plant names: Latin, English, Persian. Farhang Mo'aser

  • Norooznezhad AH, Keshavarz M, Norooznezhad F, Mansouri K (2017) Inhibition of angiogenesis: a novel effect of Zataria multiflora. Int J Hematol-Oncol Stem Cell Res 11(2):96–101

    Google Scholar 

  • Panahi Y, Davoudi SM, Beiraghdar F, Saadat A, Sahebkar A (2013) Relationship between levels of IFNγ, TNFα, and TGFβ and pruritus in sulfur mustard-exposed veterans. J Immunotoxicol 10(2):173–177

    Article  CAS  Google Scholar 

  • Panahi Y, Ghanei M, Bashiri S, Hajihashemi A, Sahebkar A (2015) Short-term curcuminoid supplementation for chronic pulmonary complications due to sulfur mustard intoxication: positive results of a randomized double-blind placebo-controlled trial. Drug Res 65(11):567–573

    CAS  Google Scholar 

  • Pharmacopoeia IH (2002) Ministry of Health and Medical Publications. Tehran, Iran

    Google Scholar 

  • Saei-Dehkordi SS, Tajik H, Moradi M, Khalighi-Sigaroodi F (2010) Chemical composition of essential oils in Zataria multiflora Boiss. From different parts of Iran and their radical scavenging and antimicrobial activity. Food Chem Toxicol 48(6):1562–1567

    Article  CAS  Google Scholar 

  • Singh G, Marimuthu P, de Heluani CS, Catalan C (2005) Chemical constituents and antimicrobial and antioxidant potentials of essential oil and acetone extract of Nigella sativa seeds. J Sci Food Agric 85(13):2297–2306

    Article  CAS  Google Scholar 

  • Soltani M, Sheikhzadeh N, Ebrahimzadeh-Mousavi H, Zargar A (2010) Effects of Zataria multiflora essential oil on innate immune responses of common carp (Cyprinus carpio). J Fish Aquatic Sci 5(3):191–199

    Article  CAS  Google Scholar 

  • Somani S, Babu S (1989) Toxicodynamics of sulfur mustard. Int J Clin Pharmacol Ther Toxicol 27(9):419–435

    CAS  Google Scholar 

  • Yaraee R, Hassan ZM, Pourfarzam S, Rezaei A, Faghihzadeh S, Ebtekar M, Soroush MR, Ardestani SK, Kazemi H, Mahmoudi M, Ghazanfari Z, Foroutan A, Jalaie S, Ghazanfari T (2013) Fibrinogen and inflammatory cytokines in spontaneous sputum of sulfur-mustard-exposed civilians—Sardasht-Iran cohort study. Int Immunopharmacol 17(3):968–973

    Article  CAS  Google Scholar 

  • Zargari A (1990) Herbal medicines, vol 83. Publication of Tehran University, Tehran

    Google Scholar 

  • Zhang L, Wang J-N, Tang J-M, Kong X, Yang JY, Zheng F, Guo LY, Huang YZ, Zhang L, Tian L, Cao SF, Tuo CH, Guo HL, Chen SY (2012) VEGF is essential for the growth and migration of human hepatocellular carcinoma cells. Mol Biol Rep 39(5):5085–5093

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohammad Hossein Boskabady.

Ethics declarations

This clinical trial was approved by the Ethical Committee of the Mashhad University of Medical Sciences (Code: 920537) in 2017, and all subjects signed informed consent, and it was emphasized that their personal information will be confidential.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible Editor: Philippe Garrigues

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khazdair, M.R., Rezaeetalab, F., Rafatpanah, H. et al. The effect of Zataria multiflora on inflammatory cytokine and respiratory symptoms in veterans exposed to sulfur mustard. Environ Sci Pollut Res 27, 22451–22460 (2020). https://doi.org/10.1007/s11356-020-08855-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-020-08855-5

Keywords

Navigation