Evaluation of the effects of overdose Acetaminophen toxicity in rats: Ozone, which can be preferred as a complementary therapy

  • Emre Kaya Firat University, Faculty of Veterinary Medicine, Department of Biochemistry. Elazig, Türkiye
  • Seval Yilmaz Firat University, Faculty of Veterinary Medicine, Department of Biochemistry. Elazig, Türkiye
  • Feyza Aksu Firat University, Faculty of Medicine, Department of Anatomy, Elazig, Türkiye
  • Ahmet Kavaklı Firat University, Faculty of Medicine, Department of Anatomy, Elazig, Türkiye
Keywords: Acetaminophen, antioxidant, ozone, oxidative stress, toxicity

Abstract

This study aims to investigate the effects of Ozone therapy used in traditional and complementary medicine on possible toxicity caused by Acetaminophen (APAP). There was no intervention in first group (control). The second group received 150 µg·kg-1 day, i.p. for three weeks of ozone, 2 g·kg-1 orally single dose APAP to third group, and APAP+Ozone to fourth group. APAP was administered on 21st day of ozone application. Malondialdehyde (MDA) levels, reduced glutathione (GSH) levels, and antioxidant enzyme activities were all measured to assess their contribution to pathogenesis of toxicity in blood tissues. Compared to the control group, the group receiving APAP showed increased MDA levels (P=0.009) and decreased GSH levels (P<0.001), as well as reduced CAT (P<0.001), GSH–Px (P<0.001) and SOD (P<0.001) enzyme activities. However, in the group treated with ozone and APAP, levels of MDA and GSH, as well as the activities of the antioxidant enzymes, were similar to those of the control group, indicating a protective effect of ozone against APAP–induced oxidative stress. In conclusion, the results of the study showed that APAP caused oxidative stress in blood tissue. The present study showed that ozone had potential protective effects against toxicity induced with APAP through various mechanisms in different cellular processes. This may be related to cytoprotective and antioxidant properties of ozone. Ozone can provide a chemical basis for some health benefits against toxicities. Ozone may be protective against APAP–induced oxidative damage. As a result, it was concluded that ozone may be a natural and effective antioxidant that can be used to reduce the toxicity caused by APAP.

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References

Lee WM. Acetaminophen toxicity: A history of serendipity and unintended consequences. Clin. Liver Dis. [Internet]. 2020; 16(1):34. doi: https://doi.org/mpnw

Xiao Q, Zhao Y, Ma L, Piao R. Orientin reverses acetaminophen–induced acute liver failure by inhibiting oxidative stress and mitochondrial dysfunction. J. Pharmacol. Sci. [Internet]. 2022; 149(1):11–19. doi: https://doi.org/mpnx

Ghanem CI, Pérez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharm. Res. [Internet]. 2016; 109:119–131. doi: https://doi.org/f8thtw

Chowdhury A, Nabila J, Temitope IA, Wang S. Current etiological comprehension and therapeutic targets of acetaminophen–induced hepatotoxicity. Pharmacol. Res. [Internet]. 2020; 161:105102. doi: https://doi.org/mpnz

Sun F, Peng Y, Li Y, Xu M, Cai T. Fenton–reaction–triggered metabolism of acetaminophen for enhanced cancer therapy. Chinese Chem. Lett. [Internet]. 2023; 34(2):107507. doi: https://doi.org/gtpjjf

Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol. Sci. [Internet]. 2002; 65(2):166–176. doi: https://doi.org/czdczc

Akgun E, Boyacioglu M, Kum S. The potential protective role of folic acid against acetaminophen–induced hepatotoxicity and nephrotoxicity in rats. Exp. Anim. [Internet]. 2021; 70(1):54–62. doi: https://doi.org/mpn2

Eshrati R, Jafari M, Gudarzi S, Nazari A, Samizadeh E, Hesami MG. Comparison of ameliorative effects of Taraxacum syriacum and N–acetylcysteine against acetaminophen–induced oxidative stress in rat liver and kidney. J. Biochem. [Internet]. 2021; 169(3):337–350. doi: https://doi.org/mpn3

Najafizadeh A, Kaeidi A, Rahmani M, Hakimizadeh E, Hassanshahi J. The protective effect of carvacrol on acetaminophen–induced renal damage in male rats. Mol. Biol. Rep. [Internet]. 2022; 49(3):1763–1771. doi: https://doi.org/mpn4

Olaniyi KS, Agunbiade TB. α–tocopherol attenuates acetaminopheninduced testicular dysfunction in adult male rats. Intern. J. Health All Sci. [Internet]. 2018; 7(1):6–11. doi: https://doi.org/mpn5

Clavo B, Martínez–Sánchez G, Rodríguez–Esparragón F, Rodríguez–Abreu D, Galván S, Aguiar–Bujanda D, Marrero–Callico G. Modulation by ozone therapy of oxidative stress in chemotherapy–induced peripheral neuropathy: The background for a randomized clinical trial. Intern. J. Mol. Sci. [Internet]. 2021; 22(6):2802. doi: https://doi.org/mpn6

Tahmasebi S, Qasim MT, Krivenkova MV, Zekiy AO, Thangavelu L, Aravindhan S, Roshangar L. The effects of oxygen–ozone therapy on regulatory T‐cell responses in multiple sclerosis patients. Cell Biol. Inter. [Internet]. 2021; 45(7):1498–1509. doi: https://doi.org/mpn7

Cattel F, Giordano S, Bertiond C, Lupia T, Corcione S, Scaldaferri M, De Rosa FG. Ozone therapy in COVID–19: A narrative review. Virus Res. [Internet]. 2021; 291:198207. doi: https://doi.org/gmnjd6

Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch. Med. Res. [Internet]. 2006; 37(4):425–435. doi: https://doi.org/bwgfx6

Delgadillo–Valero LF, Hernández–Cruz EY, Pedraza–Chaverri J. The Protective role of ozone therapy in kidney disease: A review. Life [Internet]. 2023; 13(3):752. doi: https://doi.org/mppd

Guven A, Gundogdu G, Sadir S, Topal T, Erdogan E, Korkmaz A, Surer I, Ozturk H. The efficacy of ozone therapy in experimental caustic esophageal burn. J. Ped. Surg. [Internet]. 2008; 43(9):1679–1684. doi: https://doi.org/c7sr69

Di Mauro R, Cantarella G, Bernardini R, Di Rosa M, Barbagallo I, Distefano A, Longhitano L, Vicario N, Nicolosi D, Lazzarino G, Tibullo D, Gulino ME, Spampinato M, Avola R, Li Volti G. The biochemical and pharmacological properties of ozone: the smell of protection in acute and chronic diseases. Intern. J. Mol. Sci. [Internet]. 2019; 20(3):634. doi: https://doi.org/gjrtfs

Khelfallah A, Aouay B, Kebieche M, Fetoui H. CYP2E1 inhibition and NF_κB signaling pathway are involved in the protective molecular effect of origanum floribundum against acetaminophen–induced acute hepatotoxicity in rats. Iranian J. Pharm. Res. [Internet]. 2021; 20(3):577. doi: https://doi.org/mppk

Madej P, Plewka A, Madej JA, Plewka D, Mroczka W, Wilk K, Dobrosz Z. Ozone therapy in induced endotoxemic shock. II. The effect of ozone therapy upon selected histochemical reactions in organs of rats in endotoxemic shock. Inflammation [Internet]. 2007; 30(3):69–86. doi: https://doi.org/fvbrqr

Placer ZA, Cushman L, Johnson BC. Estimation of products of lipid peroxidation in biological fluids. Anal. Biochem. [Internet]. 1966; 16(2):359–364. doi: https://doi.org/b96rpj

Ellman GL. Tissue sulfhydryl groups. Arch. Biochem. Biophys. [Internet]. 1959; 82(1):70–77. doi: https://doi.org/bz2vt8

Aebi H. Catalase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. 2nd ed. Vol 2. New York: Academic Press; 1974. p. 673–684.

Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods. 3rd ed. Orlando, FL, USA: Grune & Stratton; 1984. p. 310–311.

Sun Y, Oberly LW, Ying LA. Simple method for clinical assay of superoxide dismutase. Clin. Chem. [Internet]. 1988; 34: 497–500. https://doi.org/10.1093/clinchem/34.3.497

Frankel S, Reitman S, Sonnen AC. A textbook on laboratory procedure and their interpretation. In: Gradwohl RBH, editor. Gradwohl's Clinical Laboratory Methods and Diagnosis. St. Louis, MO, USA: C.V. Mosby; 1970. p 403–404.

Hamid A, Lee LS, Karim SR, Jufri NF. Hepatoprotective effects of zerumbone against paracetamol–induced acute hepatotoxicity in rats. Malaysian J. Med. Sci. 2018; 25(2):64–71. doi: https://doi.org/mppn

Tejo J. Curcumin, antioxidant activity, and paracetamol toxicity. Toxicol. [Internet]. 2021; 469–477. doi: https://doi.org/mppq

Bührer C, Endesfelder S, Scheuer T, Schmitz T. Paracetamol (Acetaminophen) and the developing brain. Intern. J. Mol. Sci. [Internet]. 2021; 22(20):11156. doi: https://doi.org/mppr

Jaeschke H, Ramachandran A, Chao X, Ding WX. Emerging and established modes of cell death during acetaminophen–induced liver injury. Arch. Toxicol. [Internet]. 2019; 93:3491–3502. doi: https://doi.org/gsjv5j

Abdulrazzaq AM, Badr M, Gammoh O, Abu Khalil AA, Ghanim BY, Alhussainy TM, Qinna NA. Hepatoprotective actions of ascorbic acid, alpha lipoic acid and silymarin or their combination against acetaminophen–induced hepatotoxicity in rats. Med. [Internet]. 2019; 55(5):181. doi: https://doi.org/mpps

Lalert L, Ji–au W, Srikam S, Chotipinit T, Sanguanrungsirikul S, Srikiatkhachorn A, Grand SM. Alterations in synaptic plasticity and oxidative stress following long–term paracetamol treatment in rat brain. Neurotox. Res. [Internet]. 2020; 37(2):455–468. doi: https://doi.org/mppt

Suhail M, Ahmad I. In vivo effects of acetaminophen on rat RBC and role of vitamin E. Indian J. Exp. Biol. 1995; 33(4):269–271. Cited in: PubMed; PMID 7558183.

Abdul–Hamid Z, Budin SB, Wen Jie N, Hamid A, Husain H, Mohamed J. Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract against paracetamol–induced nephrotoxicity and oxidative stress in rats. J. Zhejiang Uni. Sci. B. [Internet]. 2012; 13(3):176–185. doi: https://doi.org/f3wtm5

Kumar G, Banu GS, Kannan V, Pandian MR. Antihepatotoxic effect of beta–carotene on paracetamol induced hepatic damage in rats. Indian J. Exp. Biol. [Internet]. 2005; 43(4):351–355. Cited in: PubMed; PMID 15875720.

Kuriakose GC, Kurup MG. Antioxidant and hepatoprotective activity of Aphanizomenon flos–aquae Linn against paracetamol intoxication in rats. Indian J. Exp. Biol. 2010; 48(11):1123–1130. Cited in: PubMed; PMID 21117453.

Sakran M, Selim Y, Zidan N. A new isoflavonoid from seeds of Lepidium sativum L. and its protective effect on hepatotoxicity induced by paracetamol in male rats. Molecules. 2014; 19(10):15440–15451. doi: https://doi.org/gchmxc

Wang Y, Li D, Cheng N, Goa H, Xue X, Cao W, Sun L. Antioxidant and hepatoprotective activity of vitex honey against paracetamol induced liver damage in mice. Food Funct. [Internet]. 2015; 6:2339–2349. doi: https://doi.org/f7vxw3

Zubairi MB, Ahmed JH, Al–Haroon SS. Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol–induced hepatotoxicity in rabbits. Indian J. Pharmacol. [Internet]. 2014; 46(6):644–648. doi: https://doi.org/mppv

Chellappan DK, Ganasen S, Batumalai S, Candasamy M, Krishnappa P, Dua K, Chellian J, Gupta G. The protective action of the aqueous extract of Auricularia polytricha in paracetamol induced hepatotoxicity in rats. Recent Pat. Drug Deliv. Formulat. [Internet]. 2016; 10(1):72–76. doi: https://doi.org/f8vqjs

Bhatt S, Sharma A, Dogra A, Sharma P, Kumar A, Kotwal P, Nandi U. Glabridin attenuates paracetamol–induced liver injury in mice via CYP2E1–mediated inhibition of oxidative stress. Drug Chem. Toxicol. 2022; 45(5):2352–2360. doi: https://doi.org/grk2xn

Yılmaz S, Kaya E. [Protective effects of propolis and artichoke in cyclophosphamide–induced hemorrhagic cystitis in rats]. F. Ü. Sağ. Bil. Tıp. Derg. [Internet] 2018 [cited 18 Oct 2023]; 32(2):93–98. Turkish. Available in: https://goo.su/E8yd

Hussain Z, Khan JA, Arshad A, Asif P, Rashid H, Asrhad MI. Protective effects of Cinnamomum zeylanicum L.(Darchini) in acetaminophen–induced oxidative stress, hepatotoxicity and nephrotoxicity in mouse model. Biomed. Pharm. [Internet]. 2019; 109:2285–2292. doi: https://doi.org/gf4376

Kannappan SGP, Raghunath G, Sivanesan S, Vijayaraghavan R, Swaminathan M. Inhibition of oxidative stress, inflammation and apoptosis by Terminalia arjuna against acetaminophen–induced hepatotoxicity in Wistar albino rats. Indian J. Biochem. Biophys. [Internet]. 2020; 57(1):51–57. doi: https://doi.org/mppw

Güvenç M, Cellat M, Gökçek İ, Özkan H, Arkalı G, Yakan A, Özsoy ŞY, Aksakal M. Nobiletin attenuates acetaminophen‐induced hepatorenal toxicity in rats. J. Biochem. Mol. Toxicol. [Internet]. 2020; 34(2):e22427. doi: https://doi.org/mmw5

Tripathi SS, Singh S, Garg G, Kumar R, Verma AK, Singh AK, Bissoyi A, Rivzi SI. Metformin ameliorates acetaminophen–induced sub–acute toxicity via antioxidant property. Drug Chem. Toxicol. [Internet]. 2022; 45(1):52–60. https://doi.org/mpp2

Aycan İÖ, Tüfek A, Tokgöz O, Evliyaoğlu O, Fırat U, Kavak GÖ, Turgut H, Yüksel MU. Thymoquinone treatment against acetaminophen–induced hepatotoxicity in rats. Intern. J. Surg. [Internet]. 2014; 12(3):213–218. doi https://doi.org/gjr2q7

Eroğlu H, Makav M, Adali Y, Citil M. Effects of ozone and L–carnitine on kidney MDA, GSH, and GSHPx levels in acetaminophen toxicity. Kafkas Univ. Vet. Fak. Derg. [Internet]. 2020; 26(1): 127–134. doi: https://doi.org/mpp3

Ucar F, Taslipinar MY, Alp BF, Aydin I, Aydin FN, Agilli M, Toygar M, Ozkan E, Macit E, Oztosun M, Cayci T, Ozcan A. The effects of N–acetylcysteine and ozone therapy on oxidative stress and inflammation in acetaminophen–induced nephrotoxicity model. Renal Fail. [Internet]. 2013; 35(5):640–647. doi: https://doi.org/mpp4

Pivotto AP, Banhuk FW, Staffen IV, Daga MA, Ayala TS, Menolli RA. Clinical Uses and Molecular Aspects of Ozone Therapy: A Review. Online J. Biol. Sci. [Internet]. 2020; 20(1):37–49. doi: https://doi.org/mpp5

Weast RC, editor. Handbook of Chemistry and Physics: 1st student ed. Boca Raton, FL, USA: CRC Press; 1988.

Clavo B, Rodríguez–Esparragón F, Rodríguez–Abreu D, Martínez–Sánchez G, Llontop P, Aguiar–Bujanda D, Fernández–Pérez L, Santana–Rodríguez N. Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy–Induced Toxicity: Review and Prospects. Antioxidants [Internet]. 2019; 8(12):588. doi: https://doi.org/gntgh7

Sciorsci RL, Lillo E, Occhiogrosso L, Rizzo A. Ozone therapy in veterinary medicine: a review. Res. Vet. Sci. [Internet]. 2020; 130:240–246. https://doi.org/gnqvpw

Van der Zee J, Mulder GJ, Van Steveninck J. Acetaminophen protects human erythrocytes against oxidative stress. Chem–Biol. Interact. [Internet]. 1988; 65(1):15–23. doi: https://doi.org/ddhv5q

Published
2024-04-03
How to Cite
1.
Kaya E, Yilmaz S, Aksu F, Kavaklı A. Evaluation of the effects of overdose Acetaminophen toxicity in rats: Ozone, which can be preferred as a complementary therapy. Rev. Cient. FCV-LUZ [Internet]. 2024Apr.3 [cited 2024May17];34(1):9. Available from: https://www.produccioncientificaluz.org/index.php/cientifica/article/view/41862
Section
Veterinary Medicine