Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2023 | Research

The aqueous extract of Artemisia Absinthium L. stimulates HO-1/MT-1/Cyp450 signaling pathway via oxidative stress regulation induced by aluminium oxide nanoparticles (α and γ) animal model

Authors: Esmaeil Karami, Zahra Goodarzi, Seyed Jamaleddin Shahtaheri, Mehrafarin Kiani, Mohammad Faridan, Mahmoud Ghazi-Khansari

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Abstract

Background

This research aimed to evaluate the protective effects of Artemisia Absinthium L. (Abs) against liver damage induced by aluminium oxide nanoparticles (Al₂O₃ NPs) in rats, including both structural and functional changes associated with hepatotoxicity.

Methods

Thirty-six rats were randomly divided into six groups (n = 6). The first group received no treatment. The second group was orally administered Abs at a dose of 200 mg/kg/b.w. The third and fifth groups were injected intraperitoneally with γ-Al₂O₃ NPs and α-Al₂O₃ NPs, respectively, at a dose of 30 mg/kg/b.w. The fourth and sixth groups were pre-treated with oral Abs at a dose of 200 mg/kg/b.w. along with intraperitoneal injection of γ-Al₂O₃ NPs and α-Al₂O₃ NPs, respectively, at a dose of 30 mg/kg/b.w.

Results

Treatment with γ-Al₂O₃ NPs resulted in a significant decrease (P < 0.05) in total body weight gain, relative liver weight to body weight, and liver weight in rats. However, co-administration of γ-Al₂O₃ NPs with Abs significantly increased body weight gain (P < 0.05). Rats treated with Al₂O₃ NPs (γ and α) exhibited elevated levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), alanine transaminase (ALT), and aspartate aminotransferase (AST). Conversely, treatment significantly reduced glutathione peroxidase (GPx), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (TAC) levels compared to the control group. Furthermore, the expression of heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) mRNAs, cytochrome P450 (CYP P450) protein, and histopathological changes were significantly up-regulated in rats injected with Al₂O₃ NPs. Pre-treatment with Abs significantly reduced MDA, AST, HO-1, and CYP P450 levels in the liver, while increasing GPx and T-SOD levels compared to rats treated with Al₂O₃ NPs.

Conclusion

The results indicate that Abs has potential protective effects against oxidative stress, up-regulation of oxidative-related genes and proteins, and histopathological alterations induced by Al₂O₃ NPs. Notably, γ-Al₂O₃ NPs exhibited greater hepatotoxicity than α-Al₂O₃ NPs.

Ates M, Demir V, Arslan Z, Daniels J, Farah IO, Bogatu C. Evaluation of alpha and gamma aluminum oxide nanoparticle accumulation, toxicity, and depuration in Artemia salina larvae. Environ Toxicol. 2015;30(1):109–18.PubMed

Monteiro-Riviere NA, Oldenburg SJ, Inman AO. Interactions of aluminum nanoparticles with human epidermal keratinocytes. J Appl Toxicol. 2010;30(3):276–85.PubMed

Patlolla AK, Kumari SA, Madhusudhanachary P, Turner T, Tchounwou PB. Biochemical and histopathological evaluation of Al₂O₃ nanomaterials in kidney of Wistar rats. Curr Top Biochem Res. 2018;19:1.PubMedPubMedCentral

Yang Y, He J, Wu G, Hu J. “Thermal Stabilization Effect” of Al 2 O 3 nano-dopants improves the high-temperature dielectric performance of polyimide. Sci Rep. 2015;5(1):1–10.

Levin I, Brandon D. Metastable alumina polymorphs: crystal structures and transition sequences. J Am Ceram Soc. 1998;81(8):1995–2012.

Sliwinska A, Kwiatkowski D, Czarny P, Milczarek J, Toma M, Korycinska A, et al. Genotoxicity and cytotoxicity of ZnO and Al₂O₃ nanoparticles. Toxicol Mech Methods. 2015;25(3):176–83.PubMed

Shumakova A, Tananova O, Arianova E, Trushina É, Mustafina O, Guseva G, et al. Studies of effects of aluminum oxide nanoparticles after intragastric administration. Vopr Pitan. 2012;81(6):54–60.PubMed

Soltaninejad H, Zare-Zardini H, Hamidieh AA, Sobhan MR, Saeed-Banadaky SH, Amirkhani MA, et al. Evaluating the toxicity and histological effects of Al₂O₃ nanoparticles on bone tissue in animal model: a case-control study. J Toxicol. 2020;2020:8870530.PubMedPubMedCentral

Kumari SA, Madhusudhanachary P, Patlolla AK, Tchounwou PB. Hepatotoxicity and ultra structural changes in wistar rats treated with Al₂O₃ nanomaterials. Trends Cell Mol Biol. 2016;11:77.PubMedPubMedCentral

10.

Shrivastava R, Raza S, Yadav A, Kushwaha P, Flora SJ. Effects of sub-acute exposure to TiO2, ZnO and Al₂O₃ nanoparticles on oxidative stress and histological changes in mouse liver and brain. Drug Chem Toxicol. 2014;37(3):336–47.PubMed

11.

Prabhakar P, Reddy UA, Singh S, Balasubramanyam A, Rahman M, Indu Kumari S, et al. Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats. J Appl Toxicol. 2012;32(6):436–45.PubMed

12.

Hamza RZ, Al-Juaid NS, Althubaiti EH. Antioxidant Effect of Carnosine on Aluminum Oxide Nanoparticles (Al₂O₃-NPs)-induced hepatotoxicity and testicular structure alterations in male rats. Int J Pharmacol. 2018;14(5):740–50.

13.

Czyżowska A, Barbasz A. Effect of ZnO, TiO2, Al₂O₃ and ZrO2 nanoparticles on wheat callus cells. Acta Biochim Pol. 2019;66(3):365–70.PubMed

14.

Zhang Q, Li M, Ji J, Gao F, Bai R, Chen C, et al. In vivo toxicity of nano-alumina on mice neurobehavioral profiles and the potential mechanisms. Int J Immunopathol Pharmacol. 2011;24(1 Suppl):23S-S29.PubMed

15.

Liu N, Tang M. Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles. J Appl Toxicol. 2020;40(1):16–36.PubMed

16.

Li X, Zhang C, Bian Q, Gao N, Zhang X, Meng Q, et al. Integrative functional transcriptomic analyses implicate specific molecular pathways in pulmonary toxicity from exposure to aluminum oxide nanoparticles. Nanotoxicology. 2016;10(7):957–69.PubMed

17.

Bahadar H, Maqbool F, Niaz K, Abdollahi M. Toxicity of nanoparticles and an overview of current experimental models. Iran Biomed J. 2016;20(1):1.PubMedPubMedCentral

18.

Chen L, Yokel RA, Hennig B, Toborek M. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol. 2008;3(4):286–95.PubMedPubMedCentral

19.

Saud Alarifi DA, Alkahtani S. Nanoalumina induces apoptosis by impairing antioxidant enzyme systems in human hepatocarcinoma cells. Int J Nanomed. 2015;10:3751.

20.

Semete B. Analysis of metallothionein gene expression in oxidative stress related disorders (Doctoral dissertation, North-West University). 2004.

21.

Bansal S, Biswas G, Avadhani NG. Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity. Redox Biol. 2014;2:273–83.PubMed

22.

Li AP. Accurate prediction of human drug toxicity: a major challenge in drug development. Chem Biol Interact. 2004;150(1):3–7.PubMed

23.

Amat N, Upur H, Blažeković B. In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice. J Ethnopharmacol. 2010;131(2):478–84.PubMed

24.

Mohammadian A, Moradkhani S, Ataei S, Shayesteh TH, Sedaghat M, Kheiripour N, et al. Antioxidative and hepatoprotective effects of hydroalcoholic extract of Artemisia absinthium L. in rat. J HerbMed Pharmacol. 2016;5(1):29–32.

25.

Kasote DM, Katyare SS, Hegde MV, Bae H. Significance of antioxidant potential of plants and its relevance to therapeutic applications. Int J Biol Sci. 2015;11(8):982.PubMedPubMedCentral

26.

Bora KS, Sharma A. Neuroprotective effect of Artemisia absinthium L on focal ischemia and reperfusion-induced cerebral injury. J Ethnopharmacol. 2010;129(3):403–9.PubMed

27.

Moslemi HR, Hoseinzadeh H, Badouei MA, Kafshdouzan K, Fard RMN. Antimicrobial activity of Artemisia absinthium against surgical wounds infected by Staphylococcus aureus in a rat model. Indian J Microbiol. 2012;52(4):601–4.PubMedPubMedCentral

28.

Shafi N, Khan GA, Ghauri E. AntiulcereffectofArtemisiaabsinthium L. in rats. Biol Sci PJSIR. 2004;47(2):130–4.

29.

Wei X, Xia L, Ziyayiding D, Chen Q, Liu R, Xu X, et al. The Extracts of Artemisia absinthium L. suppress the growth of hepatocellular carcinoma cells through induction of apoptosis via endoplasmic reticulum stress and mitochondrial-dependent pathway. Molecules. 2019;24(5):913.PubMedPubMedCentral

30.

Mahmoudi M, Ebrahimzadeh M, Ansaroudi F, Nabavi S, Nabavi S. Antidepressant and antioxidant activities of Artemisia absinthium L. at flowering stage. Afr J Biotechnol. 2009;8(24):7170–5.

31.

Ali M, Abbasi BH. Production of commercially important secondary metabolites and antioxidant activity in cell suspension cultures of Artemisia absinthium L. Ind Crops Prod. 2013;49:400–6.

32.

Hussain M, Raja NI, Akram A, Iftikhar A, Ashfaq D, Yasmeen F, et al. A status review on the pharmacological implications of Artemisia absinthium: a critically endangered plant. Asian Pac J Trop Dis. 2017;7(3):185–92.

33.

Caner A, Döşkaya M, Değirmenci A, Can H, Baykan Ş, Üner A, et al. Comparison of the effects of Artemisia vulgaris and Artemisia absinthium growing in western Anatolia against trichinellosis (Trichinella spiralis) in rats. Exp Parasitol. 2008;119(1):173–9.PubMed

34.

Astghik R. Studies of the dose-dependent antioxidant activity of Artemisia absinthium extracts using in vivo model. Turkish J Biochem. 2003;28:62–224.

35.

Canadanovic-Brunet JM, Djilas SM, Cetkovic GS, Tumbas VT. Free-radical scavenging activity of wormwood (Artemisia absinthium L) extracts. J Sci Food Agric. 2005;85(2):265–72.

36.

Szopa A, Pajor J, Klin P, Rzepiela A, Elansary HO, Al-Mana FA, et al. Artemisia absinthium L.—Importance in the history of medicine, the latest advances in phytochemistry and therapeutical, cosmetological and culinary uses. Plants. 2020;9(9):1063.PubMedPubMedCentral

37.

Sagástegui-Guarniz William Antonio WA, Silva-Correa CR, Torre V-L, Víctor E, Cruzado-Razco JL, Calderón-Peña AA, et al. Hepatoprotective and nephroprotective activity of artemisia absinthium L. on diclofenac-induced toxicity in rats. Pharmacogn J. 2020;12(5):1032–41.

38.

Kharoubi O, Slimani M, Krouf D, Seddick L, Aoues A. Role of wormwood (Artemisia absinthium) extract on oxidative stress in ameliorating lead induced haematotoxicity. Afr J Tradit Complement Altern Med. 2008;5(3):263–70.PubMedPubMedCentral

39.

Kamarauskaite J, Baniene R, Raudone L, Vilkickyte G, Vainoriene R, Motiekaityte V, et al. Antioxidant and mitochondria-targeted activity of caffeoylquinic-acid-rich fractions of wormwood (Artemisia absinthium L.) and silver wormwood (Artemisia ludoviciana nutt.). Antioxidants. 2021;10(9):1405.PubMedPubMedCentral

40.

Tegtmeier M, Harnischfeger G. Methods for the reduction of thujone content in pharmaceutical preparations of Artemisia, Salvia and Thuja. Eur J Pharm Biopharm. 1994;40(5):337–40.

41.

El-Hussainy EHM, Hussein AM, Abdel-Aziz A, El-Mehasseb I. Effects of aluminum oxide (Al₂O₃) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid. Can J Physiol Pharmacol. 2016;94(08):868–78.PubMed

42.

Orct T, Jurasović J, Micek V, Karaica D, Sabolić I. Macro-and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo. J Trace Elem Med Biol. 2017;40:104–11.PubMed

43.

Zheltova AA, Kharitonova MV, Iezhitsa IN, Serebryansky EP, Evsyukov OY, Spasov AA, et al. Low magnesium diet alters distribution of macroelements and trace elements in tissues and organs of female rats. J Trace Elem Med Biol. 2017;39:36–42.PubMed

44.

Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957;28(1):56–63.PubMed

45.

Karami E, Goodarzi Z, Ghanbari A, Bandegi AR, Yosefi S, Dehdashti A. In vivo antioxidant and kidney protective potential of Atorvastatin against cadmium chloride-induced kidney injury in male Wistar rat. All Life. 2022;15(1):1025–36.

46.

Dianat M, Radmanesh E, Badavi M, Mard SA, Goudarzi G. Disturbance effects of PM10 on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia–reperfusion injury in isolated rat heart: protective role of vanillic acid. Environ Sci Pollut Res. 2016;23(6):5154–65.

47.

Pfaffl M. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45 (Find this article online).PubMedPubMedCentral

48.

Zahra G, Esmaeil K, Mohammad F, Rashidy-Pour A, Mahdi M, Mahdi A, et al. Combined effects of the exposure to silver nanoparticles and noise on hearing function and cochlea structure of the male rats. Life Sci. 2022;304:120724.PubMed

49.

Bancroft JD, Gamble M. Theory and practice of histological techniques: Elsevier health sciences. 2008.

50.

Mann PC, Vahle J, Keenan CM, Baker JF, Bradley AE, Goodman DG, et al. International harmonization of toxicologic pathology nomenclature: an overview and review of basic principles. Toxicol Pathol. 2012;40(4_suppl):7S-13S.PubMed

51.

Ezeuko Vitalis C, Nwokocha Chukwuemeka R, Mounmbegna Philippe E, Nriagu CC. Effects of Zingiber officinale on liver function of mercuric chloride-induced hepatotoxicity in adult Wistar rats. Electron J Biomed. 2007;3:40–5.

52.

Yousef M, Al-hamadani M, Kamel M. Reproductive toxicity of aluminum oxide nanoparticles and zinc oxide nanoparticles in male rats. Nanoparticle. 2019;1(1):3.

53.

Mazhar MW. Antioxidant and protective effect of “Artemesia absinthium” and “Nigella sativa” on Albino mice mode of hepatic injury. J Basic Clin Pharm. 2022;13(2):136–9.

54.

Alghriany AA, Omar HE-dM, Mahmoud AM, Atia MM. Assessment of the toxicity of aluminum oxide and its nanoparticles in the bone marrow and liver of male mice: ameliorative efficacy of curcumin nanoparticles. ACS Omega. 2022;7(16):13841–52.PubMedPubMedCentral

55.

Canli EG, Ila HB, Canli M. Response of the antioxidant enzymes of rats following oral administration of metal-oxide nanoparticles (Al₂O₃, CuO, TiO2). Environ Sci Pollut Res. 2019;26(1):938–45.

56.

Zarezade V, Moludi J, Mostafazadeh M, Mohammadi M, Veisi A. Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats. Avicenna J Phytomed. 2018;8(1):51.PubMedPubMedCentral

57.

Pereira A, Fraga-Corral M, García-Oliveira P, Jimenez-Lopez C, Lourenço-Lopes C, Carpena M, et al. Culinary and nutritional value of edible wild plants from northern Spain rich in phenolic compounds with potential health benefits. Food Funct. 2020;11(10):8493–515.PubMed

58.

Ábrahám S, Hermesz E, Szabó A, Ferencz Á, Jancsó Z, Duda E, et al. Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice. Life Sci. 2012;90(3–4):140–6.PubMed

59.

Nath KA. Heme oxygenase-1 and acute kidney injury. Curr Opin Nephrol Hypertens. 2014;23(1):17.PubMedPubMedCentral

60.

Horie M, Fukui H, Endoh S, Maru J, Miyauchi A, Shichiri M, et al. Comparison of acute oxidative stress on rat lung induced by nano and fine-scale, soluble and insoluble metal oxide particles: NiO and TiO2. Inhalation Toxicol. 2012;24(7):391–400.

61.

Ioannides C, V Lewis DF. Cytochromes P450 in the bioactivation of chemicals. Curr Top Med Chem. 2004;4(16):1767–88.PubMed

62.

Kim D-H. Gut microbiota-mediated drug-antibiotic interactions. Drug Metab Dispos. 2015;43(10):1581–9.PubMed

63.

Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450–mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther. 2009;85(4):434–8.PubMed

64.

Robertson G, Leclercq I, Farrell GC. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol. 2001;281(5):G1135–9.PubMed

65.

Gerbal-Chaloin S, Iankova I, Maurel P, Daujat-Chavanieu M. Nuclear receptors in the cross-talk of drug metabolism and inflammation. Drug Metab Rev. 2013;45(1):122–44.PubMed

66.

Wang Y-M, Ong SS, Chai SC, Chen T. Role of CAR and PXR in xenobiotic sensing and metabolism. Expert Opin Drug Metab Toxicol. 2012;8(7):803–17.PubMedPubMedCentral

67.

Kawahara M. Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases. J Alzheimers Dis. 2005;8(2):171–82.PubMed

68.

Amjad S, Umesalma S. Centella asiatica extracts regulates aluminium chloride-induced neurotoxicity in rats: impact on inflammation, apoptosis and biogenic amine levels. J Pharmacol Pharmaceut Pharma Covigil. 2018;2:007.

69.

M’rad I, Jeljeli M, Rihane N, Hilber P, Sakly M, Amara S. Aluminium oxide nanoparticles compromise spatial learning and memory performance in rats. EXCLI J. 2018;17:200.PubMedPubMedCentral

70.

Exley C, Clarkson E. Aluminium in human brain tissue from donors without neurodegenerative disease: A comparison with Alzheimer’s disease, multiple sclerosis and autism. Sci Rep. 2020;10(1):1–7.

71.

Mustafa SA. Histopathology and heavy metal bioaccumulation in some tissues of Luciobarbus xanthopterus collected from Tigris River of Baghdad, Iraq. Egypt J Aquati Res. 2020;46(2):123–9.

72.

Hadi AHA, Jaffat HS. Effect of aluminum-containing antacid on sperm parameters and testicular structure in male rats. Int J PharmTech Res. 2016;9:267–71.

73.

Siddique NA, Mujeeb M, Najmi AK, Aftab A, Aslam J. Free radical scavenging and hepatoprotective activity of Aegle marmelos (linn.) corr leaves against carbon tetrachloride. Int J Compr Pharm. 2011;2(08):1–6.

Title: The aqueous extract of Artemisia Absinthium L. stimulates HO-1/MT-1/Cyp450 signaling pathway via oxidative stress regulation induced by aluminium oxide nanoparticles (α and γ) animal model
Authors: Esmaeil Karami
Zahra Goodarzi
Seyed Jamaleddin Shahtaheri
Mehrafarin Kiani
Mohammad Faridan
Mahmoud Ghazi-Khansari
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04121-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The aqueous extract of Artemisia Absinthium L. stimulates HO-1/MT-1/Cyp450 signaling pathway via oxidative stress regulation induced by aluminium oxide nanoparticles (α and γ) animal model

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Arts-based therapies, practices, and interventions in health

Tracking the effect of roasting and fermentation on the metabolites of licorice root (Glycyrrhiza glabra L.) using UPLC-MS analysis combined with multivariate statistical analysis

Melittin as a safe compound to BALB/c mice immune system; a tiered approach immunotoxicity screening

Correction: Baicalin promotes apoptosis and inhibits proliferation and migration of hypoxia-induced pulmonary artery smooth muscle cells by up-regulating A2a receptor via the SDF-1/CXCR4 signaling pathway

Electroacupuncture for the management of symptom clusters in cancer patients and survivors (EAST)

Retraction Note: Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer’s disease- like alterations through multi-targeting activities in two animal models