Antioxidant, anti-apoptotic and anti-inflammatory effects of acacetin against deltamethrin-induced hepatotoxicity in mice: a biochemical and histopathological study

authors:

avatar Ali Ghanbari ORCID , avatar Cyrus Jalili ORCID , avatar Kaveh Shahveisi , avatar Farshid Raissi , avatar Fatemeh Mazini , avatar Nasim Akhshi ORCID , *

Koomesh: Vol.25, issue 4; 486-494
published online: December 03, 2023
article type: Research Article
received: August 02, 2023
accepted: September 03, 2023

how to cite: Ghanbari A, Jalili C, Shahveisi K, Raissi F, Mazini F, et al. Antioxidant, anti-apoptotic and anti-inflammatory effects of acacetin against deltamethrin-induced hepatotoxicity in mice: a biochemical and histopathological study. koomesh. 2023;25(4):e152847. 

Abstract

Introduction: Agricultural pesticides are widely used all over the world. Relatively, Deltamethrin is a synthetic pyrethroid insecticide used in agriculture. Oxidative stress induction is one of its toxicity mechanisms. It has been found that natural compounds with antioxidant properties play an essential role in maintaining people's health against the dangers of chemicals such as pesticides. Therefore, the present study aimed to investigate the role of acacetin; a natural secondary metabolite, in deltamethrin-induced liver damage in rats. Materials and Methods: Thirty-two male Balb/C mice were randomly divided into four groups (8 mice in each group) containing control, acacetin (50 mg/kg), deltamethrin (5 mg/kg/day), and deltamethrin+acacetin. The mice for 2 weeks received 0.01% Dimethyl sulfoxide or deltamethrin (5 mg/kg/day) by gavage and acacetin (50 mg/kg) intraperitoneally. The histopathological changes in liver tissue, serum levels of liver-related enzymes, tissue values of total antioxidant capacity, malondialdehyde, number of apoptotic cells, and inflammatory cytokines were evaluated. Results: The total antioxidant capacity of liver tissue in the deltamethrin group was significantly lower than the control group. In contrast, other parameters in the deltamethrin group were considerably higher than the control group (P<0.01). A significant increase in the total antioxidant capacity of liver tissue was seen in the deltamethrin+acacetin group compared to the deltamethrin group (P<0.01). At the same time, other studied parameters showed a significant decrease in this comparison (P<0.01). Conclusion: Acacetin with its antioxidant, anti-apoptotic, and anti-inflammatory properties improves liver tissue damage caused by deltamethrin.

References

  • 1.

    darbandi z, Zazouli Ma, Shokrzadeh M, Mousavi nasab n, rostamali e. Photocatalytic degradation of diazinon using Zno/TiO2 nano-photocatalysts. Koomesh 2016; 18: 343-349. (Persian).

  • 2.

    Rahbari A, Nazem H, Fazilati M, Mehri F. Protective effect of resveratrol against sub-acute diazinon-induced oxidative stress in rat kidney. Koomesh 2021; 23: 794-800. (Persian).

  • 3.

    Soderlund D, Knipple D. The molecular biology of knockdown resistance to pyrethroid insecticides. Insect Biochem Mol Biol 2003; 33: 563-577.

  • 4.

    Saillenfait AM, Ndiaye D, Sabat JP. Pyrethroids: exposure and health effects-an update. Int J Hyg Environ Health 2015; 218: 281-292.

  • 5.

    Abdallah FB, Hamden K, GaleraudDenis I, El Feki A, KeskesAmmar L. An in vitro study on reproductive toxicology of deltamethrin on rat spermatozoa. Andrologia 2010; 42: 254-259.

  • 6.

    Abdel-Daim M, El-Bialy BE, Rahman HG, Radi AM, Hefny HA, Hassan AM. Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: biochemical and histopathological studies. Biomed Pharmacother 2016; 77: 79-85.

  • 7.

    Abdou RH, Abdel-Daim MM. Alpha-lipoic acid improves acute deltamethrin-induced toxicity in rats. Can J Physiol Pharmacol 2014; 92: 773-779.

  • 8.

    Ncir M, Ben Salah G, Kamoun H, Makni Ayadi F, Khabir A, El Feki A, et al. Histopathological, oxidative damage, biochemical, and genotoxicity alterations in hepatic rats exposed to deltamethrin: modulatory effects of garlic (Allium sativum). Can J Physiol Pharmacol 2016; 94: 571-578.

  • 9.

    Nieradko-Iwanicka B, Borzcki A. Subacute poisoning of mice with deltamethrin produces memory impairment, reduced locomotor activity, liver damage and changes in blood morphology in the mechanism of oxidative stress. Pharmacol Rep 2015; 67: 535-541.

  • 10.

    Abdel-Daim MM, El-Ghoneimy A. Synergistic protective effects of ceftriaxone and ascorbic acid against subacute deltamethrin-induced nephrotoxicity in rats. Ren Fail 2015; 37: 297-304.

  • 11.

    Amin KA, Hashem KS. Deltamethrin-induced oxidative stress and biochemical changes in tissues and blood of catfish (Clarias gariepinus): antioxidant defense and role of alpha-tocopherol. BMC Vet Res 2012; 8: 1-8.

  • 12.

    Ncir M, Saoudi M, Sellami H, Rahmouni F, Lahyani A, Makni Ayadi F, et al. In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney. Arch Physiol Biochem 2018; 124: 207-217.

  • 13.

    Osama E, Galal AA, Abdalla H, ElSheikh SM. Chlorella vulgaris ameliorates testicular toxicity induced by deltamethrin in male rats via modulating oxidative stress. Andrologia 2019; 51: e13214.

  • 14.

    Behtaripour M, Meshkini S, Tafi AA. The acute and chronic effects of Deltamethrin insecticide on brain acetylcholinesterase, blood catalase enzymes and histopathology of Carassius auratus in the presence of vitamin C. J Aquac Res Dev 2022; 16: 49-62.##https://doi.org/10.52547/aqudev.16.2.49.

  • 15.

    Ozkan F, Gndz SG, Berkz M, Hunt AO, Yaln S. The protective role of ascorbic acid (vitamin C) against chlorpyrifos-induced oxidative stress in Oreochromis niloticus. Fish Phys Biochem 2012; 38: 635-643.

  • 16.

    Abdel-Daim MM, Abd Eldaim MA, Mahmoud MM. Trigonella foenum-graecum protection against deltamethrin-induced toxic effects on haematological, biochemical, and oxidative stress parameters in rats. Can J Physiol Pharmacol 2014; 92: 679-685.

  • 17.

    Abdel-Daim MM, Abdelkhalek NK, Hassan AM. Antagonistic activity of dietary allicin against deltamethrin-induced oxidative damage in freshwater Nile tilapia; Oreochromis niloticus. Ecotoxicol Environ Saf 2015; 111: 146-152.

  • 18.

    Shivanoor SM, David M. Protective role of turmeric against deltamethrin induced renal oxidative damage in rats. Biomed Prev Nutr 2014; 4: 543-553.##https://doi.org/10.1016/j.bionut.2014.08.007.

  • 19.

    Mekircha F, Chebab S, Gabbianelli R, Leghouchi E. The possible ameliorative effect of Olea europaea L. oil against deltamethrin-induced oxidative stress and alterations of serum concentrations of thyroid and reproductive hormones in adult female rats. Ecotoxicol Environ Saf 2018; 161: 374-382.

  • 20.

    Singh S, Gupta P, Meena A, Luqman S. Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders. Food Chemical Toxicol 2020; 145: 111708.

  • 21.

    Chang W, Wu QQ, Xiao Y, Jiang XH, Yuan Y, Zeng XF, et al. Acacetin protects against cardiac remodeling after myocardial infarction by mediating MAPK and PI3K/Akt signal pathway. J Pharmacol Sci 2017; 135: 156-163.

  • 22.

    Semwal RB, Semwal DK, Combrinck S, Trill J, Gibbons S, Viljoen A. Acacetin-A simple flavone exhibiting diverse pharmacological activities. Phytochem Lett 2019; 32: 56-65.##https://doi.org/10.1016/j.phytol.2019.04.021.

  • 23.

    Jiang Z, Sun H, Miao J, Sheng Q, Xu J, Gao Z, et al. The natural flavone acacetin protects against high-fat diet-induced lipid accumulation in the liver via the endoplasmic reticulum stress/ferroptosis pathway. Biochem Biophys Res Commun 2023; 640: 183-191.

  • 24.

    Liou CJ, Wu SJ, Shen SC, Chen LC, Chen YL, Huang WC. Acacetin protects against non-alcoholic fatty liver disease by regulating lipid accumulation and inflammation in mice. Int J Mol Sci 2022; 23: 10.

  • 25.

    Jalili C, Akhshi N, Raissi F, Shiravi A, Alvani A, Vaezi G, et al. Acacetin alleviates hepatitis following renal ischemia-reperfusion in male Balb/C mice by antioxidants regulation and inflammatory markers suppression. J Invest Surg 2021; 34: 495-503.

  • 26.

    Alvani A, Jalili C, Shiravi A, Vaezi G, Ghanbari A. Acacetin Inhibits Oxidative Stress and Inflammation in Renal Ischemia-Reperfusion Injury. Jentashapir J Cell Mol Biol 2023; 14:##https://doi.org/10.5812/jjcmb-136185.

  • 27.

    Simsek H, Akaras N. Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. Int J Med Biochem 2023; 6: 96-103.##https://doi.org/10.14744/ijmb.2023.07830.

  • 28.

    Wu WY, Cui YK, Li YD, Li G, Wu Y, Wang Y, et al. Molecular Mechanism of the Natural Flavone Acacetin in Cardioprotection Against Hypoxia-Reoxygenation Injury. Circulation 2017; 136: A17254-A17254.

  • 29.

    Rehman H, Ali M, Atif F, Kaur M, Bhatia K, Raisuddin S. The modulatory effect of deltamethrin on antioxidants in mice. Clin Chim Acta 2006; 369: 61-65.

  • 30.

    Ben Slima A, Ali MB, Barkallah M, Traore AI, Boudawara T, Allouche N, et al. Antioxidant properties of Pelargonium graveolens L'Her essential oil on the reproductive damage induced by deltamethrin in mice as compared to alpha-tocopherol. Lipids Health Dis 2013; 12: 1-9.

  • 31.

    Jalili C, Farzaei MH, Rashidi I, Mohammadnezamian A, Ghanbari A. Royal jelly protects dichlorvos liver-induced injury in male Wistar rats. Res Pharmace Sci 2022; 17: 209-218.

  • 32.

    Trocha M, Merwid-Ld A, Pieniewska M, Kwiatkowska J, Fereniec-Gobiewska L, Kowalski P, et al. Age-related differences in function and structure of rat livers subjected to ischemia/reperfusion. Arch Med Sci 2018; 14: 388-395.

  • 33.

    Shahneh FZ, Valiyari S, Azadmehr A, Hajiaghaee R, Yaripour S, Bandehagh A, et al. Inhibition of growth and induction of apoptosis in fibrosarcoma cell lines by Echinophora platyloba DC: in vitro analysis. Adv Pharmacol Sci 2013; 2013: 512931.

  • 34.

    Ghanbari A, Jalili C, Salahshoor MR, Javanmardy S, Ravankhah S, Akhshi N. Harmine mitigates cisplatin-induced renal injury in male mice through antioxidant, anti-inflammatory, and anti-apoptosis effects. Res Pharmace Sci 2022; 17: 417-427.

  • 35.

    Samiei S, Khadem M, Pourbabaki R, Ghazi-Khansari M, Shahtaheri SJ. Protective effect of salvia officinalis extract on deltamethrin-induced hepatotoxicity in rats. J Mazandaran Univ Med Sci 2019; 29: 134-140. (Persian).

  • 36.

    Samiei S, Pourbabaki R, Khadem M, Shahtaheri SJ. Antioxidant and protective effects of plant extract against deltamethrin-induced oxidative stress in liver and kidney: A review. Razi J Med Sci 2020; 27: 25-39. (Persian).

  • 37.

    Mokhtari M, Shariati M, Azarnoosh Z. Gabergolyn effect on liver enzymes and serum proteins in rats. J Shahrekord Univ Med Sci 2010; 12: 45-50. (Persian).

  • 38.

    Li S, Zheng X, Zhang X, Yu H, Han B, Lv Y, et al. Exploring the liver fibrosis induced by deltamethrin exposure in quails and elucidating the protective mechanism of resveratrol. Ecotoxicol Environ Saf 2021; 207: 111501.

  • 39.

    Mohafrash SMM, Mossa A-TH. Herbal syrup from chicory and artichoke leaves ameliorate liver damage induced by deltamethrin in weanling male rats. Environ Sci Pollut Res Int 2020; 27: 7672-7682.

  • 40.

    Khalatbary AR, Ghabaee DN, Ahmadvand H, Amiri FT, Lehi ST. Deltamethrin-induced hepatotoxicity and virgin olive oil consumption: an experimental study. Iran J Med Sci 2017; 42: 586. (Persian).

  • 41.

    Shokri V, Jalili C, Raissi F, Akhshi N, Ghanbari A. Evaluating the effects of acacetin versus a low dose of cisplatin drug on male reproductive system and kidney in mice: with emphasis on inflammation process. Andrologia 2020; 52: e13444.##https://doi.org/10.1111/and.13444.

  • 42.

    Khalatbary AR, Ahmadvand, Hassan, Ghabaee DNZ, Malekshah AK, Navazesh A. Virgin olive oil ameliorates deltamethrin-induced nephrotoxicity in mice: A biochemical and immunohistochemical assessment. Toxicol Rep 2016; 3: 584-590.

  • 43.

    Maalej A, Mahmoudi A, Bouallagui Z, Fki I, Marrekchi R, Sayadi S. Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis. Food Chem Toxicol 2017; 106: 455-465.

  • 44.

    Refaie AA-E, Mohafrash SMM, Ibrahim AW, Mossa A-TH. Sub-acute 28-days Oral toxicity study of deltamethrin on female rats and the protective role of moringa tea. Trends Appl Sci Res 2017; 12: 10-17.##https://doi.org/10.3923/tasr.2017.10.17.

  • 45.

    Rjeibi I, Saad AB, Hfaiedh N. Oxidative damage and hepatotoxicity associated with deltamethrin in rats: The protective effects of Amaranthus spinosus seed extract. Biomed Pharmacother 2016; 84: 853-860.

  • 46.

    Saoudi M, Badraoui R, Bouhajja H, Ncir M, Rahmouni F, Grati M, et al. Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Biomed Pharmacother 2017; 94: 955-963.

  • 47.

    Kkler S, Kandemir FM, zdemir S, omakl S, Caglayan C. Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis. Environ Sci Pollut Res 2021; 28: 62975-62990.

  • 48.

    Birsen A. Effects of thiacloprid, deltamethrin and their combination on oxidative stress in lymphoid organs, polymorphonuclear leukocytes and plasma of rats. Pestic Biochem Phys 2011; 100: 165-171.##https://doi.org/10.1016/j.pestbp.2011.03.006.

  • 49.

    Hazarika A, Sarkar S, Hajare S, Kataria M, Malik J. Influence of malathion pretreatment on the toxicity of anilofos in male rats: a biochemical interaction study. Toxicology 2003; 185: 1-8.

  • 50.

    Shiravi A, Jalili C, Vaezi G, Ghanbari A, Alvani A. Acacetin attenuates renal damage-induced by ischemia-reperfusion with declining apoptosis and oxidative stress in mice. Int J Prev Med 2020; 11: 22.