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Protective effects of jervine purified from Veratrum album on paracetamol-induced liver toxicity in rats

Year 2024, Volume: 49 Issue: 1, 150 - 158, 29.03.2024
https://doi.org/10.17826/cumj.1398401

Abstract

Purpose: Since paracetamol toxicity is a very common type of poisoning, we planned to investigate whether Jervine has an effect on paracetamol toxicity by utilizing its anti-inflammatory effect.
Materials and Methods: In our study, 42 Sprague Dawley rats of 8 weeks of age were used. Seven groups were formed with 6 animals in each group. At the 24th hour of the study, all groups underwent laparotomy under anesthesia, and liver dissection was performed. Hematoxylin and Eosin (H&E) staining was performed to evaluate liver histopathology. SOD, CAT, GSH, and MDA levels were analyzed biochemically.
Results: Histopathological, while liver tissues were normal in the control group, we observed degeneration areas, inflammation, and hemorrhage in the paracetamol group. Jervine reduced the severity of paracetamol toxicity and prevented liver damage. Jervine significantly increased SOD levels. Paracetamol administration significantly decreased CAT levels. Paracetamol significantly decreased GSH levels compared to the control group.
Conclusion: Jervine reduced the adverse effects of paracetamol toxicity on liver tissue, such as degeneration, inflammation, and hemorrhage. Jervine increased antioxidant activity and reduced the harmful effects of NAPQI, the toxic metabolite of paracetamol, on liver tissue.

Ethical Statement

Author Contributions: Concept/Design :SY,MY; Data acquisition:SY; Data analysis and interpretation:TA,LD,AAK; Drafting manuscript:SB; Critical revision of manuscript:İY; Final approval and accountability:SY; Technical or material support:SY; Supervision:SAB; Ethical Approval: With decision 2021-129, the Kafkas University Local Ethics Committee for Animal Experiments gave its consent. Peer-review: Externally peer-reviewed. Conflict of Interest: Authors declared no conflict of interest. Financial Disclosure: The authors have declared that they do not receive financial support

References

  • Soliman AM, Rizk HA, Shalaby MA, Elkomy AA. Mechanisms of hepato-renal protective activity of Ocimum basilicum leaf extract against paracetamol toxicity in rat model. Adv Anim Vet Sci. 2020;8:385-91.
  • Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH et al. Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother. 2021;140:111732.
  • Ghaffar UB.Tadvi NA. Paracetamol toxicity: a review. J Contemp Med A Dent. 2014;2:12-5.
  • McGregor AH, More LJ, Simpson KJ.Harrison DJ. Liver death and regeneration in paracetamol toxicity. Hum Exp Toxicol. 2003;22:221-7.
  • Ibrahim T, Agnihotri S.Agnihotri AK. Paracetamol toxicity-an overview. Emergency Medicine. 2013;3:1-3.
  • Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, di Luca NM et al. Hepatotoxicity of paracetamol and related fatalities. Eur Rev Med Pharmacol Sci. 2017;21:95-101.
  • El Menyiy N, Al-Waili N, El Ghouizi A, Al-Waili W.Lyoussi B. Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats. Nutr Res Pract. 2018;12:535-40.
  • Herzenberg LA. History of N-acetylcysteine. In The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine (Eds RE Frye, M Berk):3-15. Cham, Springer, 2018.
  • Dumlu FA, Aydin T, Odabasoglu F, Berktas OA, Kutlu Z, Erol HS et al. Anti-inflammatory and antioxidant properties of Jervine, a sterodial alkaloid from rhizomes of Veratrum album. Phytomedicine. 2019;55:191-9.
  • Yakan S, Aydin T, Gulmez C, Ozden O, Eren Erdogan K, Daglioglu YK et al. The protective role of Jervine against radiation-induced gastrointestinal toxicity. J Enzyme Inhib Med Chem. 2019;34:789-98.
  • Ali RA, Choudhary MI, Sener B.Turkoz S. New steroidal alkaloids from rhizomes of Veratrum album. Journal of Natural Products. 1992;55:565-70.
  • Shang Y, Du Q, Liu S, Staadler M, Wang S.Wang D. Antitumor activity of isosteroidal alkaloids from the plants in the genus veratrum and fritillaria. Curr Protein Pept Sci. 2018;19:302-10.
  • Kul'kova VV, Shakirov R.D'Yakonov AL. Steroid alkaloids of the plant and animal Kingdoms. Chemistry of natural compounds. 1999;35:107-49.
  • Aydin T, Cakir A, Kazaz C, Bayrak N, Bayir Y.Taşkesenligil Y. Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado potato beetle, Leptinotarsa decemlineata. Chem Biodivers. 2014;11:1192-204.
  • Sahin L, Toktay E, Yayla M, Kilicle PA, Harmankaya A, Cem O et al. The effect of dragon fruit extract on experimental mesentery arterial ischemia-reperfusion in rats. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2021;27:575-81.
  • Sun Y, Oberley LW.Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.
  • Campo GM, Avenoso A, Campo S, Ferlazzo AM, Micali C, Zangh L et al. Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury. Life Sci. 2004;74:1289-305.
  • Sedlak J.Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205.
  • Ohkawa H, Ohishi N.Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
  • Brune K, Renner B.Tiegs G. Acetaminophen/paracetamol: A history of errors, failures and false decisions. Eur J Pain. 2015;19:953-65.
  • Alvarellos ML, McDonagh EM, Patel S, McLeod HL, Altman RB.Klein TE. PharmGKB summary: succinylcholine pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2015;25:622-30.
  • Wang M, Liu CY, Wang T, Yu HM, Ouyang SH, Wu YP et al. (+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis. Cell Death Dis. 2020;11:781.
  • Xu Y, Ding J, An JN, Qu YK, Li X, Ma XP et al. Effect of the interaction of veratrum nigrum with panax ginseng on estrogenic activity in vivo and in vitro. Sci Rep. 2016;6:26924.
  • Li Q, Yang KX, Zhao YL, Qin XJ, Yang XW, Liu L et al. Potent anti-inflammatory and analgesic steroidal alkaloids from Veratrum taliense. J Ethnopharmacol. 2016;179:274-9.
  • Tang J, Li HL, Shen YH, Jin HZ, Yan SK, Liu XH et al. Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum. Phytother Res. 2010;24:821-6.
  • Nguyen NT, Du K, Akakpo JY, Umbaugh DS, Jaeschke H.Ramachandran A. Mitochondrial protein adduct and superoxide generation are prerequisites for early activation of c-jun N-terminal kinase within the cytosol after an acetaminophen overdose in mice. Toxicol Lett. 2021;338:21-31.
  • Manyike PT, Kharasch ED, Kalhorn TF.Slattery JT. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther. 2000;67:275-82.
  • McGill MR.Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013;30:2174-87.
  • Bi H, Li F, Krausz KW, Qu A, Johnson CH.Gonzalez FJ. Targeted metabolomics of serum acylcarnitines evaluates hepatoprotective effect of wuzhi tablet (schisandra sphenanthera extract) against acute acetaminophen toxicity. Evid Based Complement Alternat Med. 2013;2013:985257.
  • Mutlib AE, Goosen TC, Bauman JN, Williams JA, Kulkarni S.Kostrubsky S. Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity. Chem Res Toxicol. 2006;19:701-9.
  • Hinson JA, Reid AB, McCullough SS.James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev. 2004;36:805-22.
  • Wang ZZ, Zhao WJ, Zhang XS, Tian XF, Wang YZ, Zhang F et al. Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver. World J Gastroenterol. 2007;13:564-71.
  • Sandilands EA.Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009;47:81-8.

Sıçanlarda parasetamolle indüklenen karaciğer toksisitesi üzerine Veratrum album bitkisinden saflaştırılan jervinin koruyucu etkisi

Year 2024, Volume: 49 Issue: 1, 150 - 158, 29.03.2024
https://doi.org/10.17826/cumj.1398401

Abstract

Amaç: Parasetamol toksisitesi de çok yaygın bir zehirlenme tipi olduğundan dolayı bizde jervinin antiinflamatuvar etkisinden faydalanarak parasetamol toksisitesi üzerinde etkisinin olup olmadığını araştırmayı planladık.
Gereç ve Yöntem: Çalışmamızda 42 adet Sprague Dawley cinsi 8 haftalık sıçan kullanıldı. Her grupta 6 dişi hayvan olacak şekilde 7 grup oluşturuldu. Çalışmanın 24. saatinde tüm gruplara anestezi altında laparotomi uygulandı ve karaciğer diseksiyonu yapıldı. Karaciğer histopatolojisini değerlendirmek için Hematoksilen ve Eozin (H&E) boyama yapıldı. Biyokimyasal olarak SOD, CAT, GSH ve MDA seviyelerine bakıldı.
Bulgular: Histopatolojik olarak kontrol grubunda karaciğer dokuları normal iken, parasetamol grubunda dejenerasyon alanları, enflamasyon ve hemoraji gözlemledik. Jervin parasetamol toksisitesinin şiddetini azaltmış ve karaciğer hasarını önlemiştir. Jervin SOD seviyelerini önemli ölçüde artırmıştır. Parasetamol uygulaması CAT seviyelerini önemli ölçüde azaltmıştır. Parasetamol, kontrol grubuna kıyasla GSH seviyelerini önemli ölçüde azaltmıştır.
Sonuç: Çalışmamız, Jervinin parasetamol toksisitesinin karaciğer dokusu üzerindeki dejenerasyon, inflamasyon ve hemoraji gibi olumsuz etkilerini azalttığını ortaya koymuştur. Jervin antioksidan aktiviteyi arttırmış ve parasetamolün toksik metaboliti olan NAPQI'nin karaciğer dokusu üzerindeki zararlı etkilerini azaltmıştı

References

  • Soliman AM, Rizk HA, Shalaby MA, Elkomy AA. Mechanisms of hepato-renal protective activity of Ocimum basilicum leaf extract against paracetamol toxicity in rat model. Adv Anim Vet Sci. 2020;8:385-91.
  • Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH et al. Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother. 2021;140:111732.
  • Ghaffar UB.Tadvi NA. Paracetamol toxicity: a review. J Contemp Med A Dent. 2014;2:12-5.
  • McGregor AH, More LJ, Simpson KJ.Harrison DJ. Liver death and regeneration in paracetamol toxicity. Hum Exp Toxicol. 2003;22:221-7.
  • Ibrahim T, Agnihotri S.Agnihotri AK. Paracetamol toxicity-an overview. Emergency Medicine. 2013;3:1-3.
  • Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, di Luca NM et al. Hepatotoxicity of paracetamol and related fatalities. Eur Rev Med Pharmacol Sci. 2017;21:95-101.
  • El Menyiy N, Al-Waili N, El Ghouizi A, Al-Waili W.Lyoussi B. Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats. Nutr Res Pract. 2018;12:535-40.
  • Herzenberg LA. History of N-acetylcysteine. In The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine (Eds RE Frye, M Berk):3-15. Cham, Springer, 2018.
  • Dumlu FA, Aydin T, Odabasoglu F, Berktas OA, Kutlu Z, Erol HS et al. Anti-inflammatory and antioxidant properties of Jervine, a sterodial alkaloid from rhizomes of Veratrum album. Phytomedicine. 2019;55:191-9.
  • Yakan S, Aydin T, Gulmez C, Ozden O, Eren Erdogan K, Daglioglu YK et al. The protective role of Jervine against radiation-induced gastrointestinal toxicity. J Enzyme Inhib Med Chem. 2019;34:789-98.
  • Ali RA, Choudhary MI, Sener B.Turkoz S. New steroidal alkaloids from rhizomes of Veratrum album. Journal of Natural Products. 1992;55:565-70.
  • Shang Y, Du Q, Liu S, Staadler M, Wang S.Wang D. Antitumor activity of isosteroidal alkaloids from the plants in the genus veratrum and fritillaria. Curr Protein Pept Sci. 2018;19:302-10.
  • Kul'kova VV, Shakirov R.D'Yakonov AL. Steroid alkaloids of the plant and animal Kingdoms. Chemistry of natural compounds. 1999;35:107-49.
  • Aydin T, Cakir A, Kazaz C, Bayrak N, Bayir Y.Taşkesenligil Y. Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado potato beetle, Leptinotarsa decemlineata. Chem Biodivers. 2014;11:1192-204.
  • Sahin L, Toktay E, Yayla M, Kilicle PA, Harmankaya A, Cem O et al. The effect of dragon fruit extract on experimental mesentery arterial ischemia-reperfusion in rats. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2021;27:575-81.
  • Sun Y, Oberley LW.Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.
  • Campo GM, Avenoso A, Campo S, Ferlazzo AM, Micali C, Zangh L et al. Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury. Life Sci. 2004;74:1289-305.
  • Sedlak J.Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205.
  • Ohkawa H, Ohishi N.Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
  • Brune K, Renner B.Tiegs G. Acetaminophen/paracetamol: A history of errors, failures and false decisions. Eur J Pain. 2015;19:953-65.
  • Alvarellos ML, McDonagh EM, Patel S, McLeod HL, Altman RB.Klein TE. PharmGKB summary: succinylcholine pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2015;25:622-30.
  • Wang M, Liu CY, Wang T, Yu HM, Ouyang SH, Wu YP et al. (+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis. Cell Death Dis. 2020;11:781.
  • Xu Y, Ding J, An JN, Qu YK, Li X, Ma XP et al. Effect of the interaction of veratrum nigrum with panax ginseng on estrogenic activity in vivo and in vitro. Sci Rep. 2016;6:26924.
  • Li Q, Yang KX, Zhao YL, Qin XJ, Yang XW, Liu L et al. Potent anti-inflammatory and analgesic steroidal alkaloids from Veratrum taliense. J Ethnopharmacol. 2016;179:274-9.
  • Tang J, Li HL, Shen YH, Jin HZ, Yan SK, Liu XH et al. Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum. Phytother Res. 2010;24:821-6.
  • Nguyen NT, Du K, Akakpo JY, Umbaugh DS, Jaeschke H.Ramachandran A. Mitochondrial protein adduct and superoxide generation are prerequisites for early activation of c-jun N-terminal kinase within the cytosol after an acetaminophen overdose in mice. Toxicol Lett. 2021;338:21-31.
  • Manyike PT, Kharasch ED, Kalhorn TF.Slattery JT. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther. 2000;67:275-82.
  • McGill MR.Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013;30:2174-87.
  • Bi H, Li F, Krausz KW, Qu A, Johnson CH.Gonzalez FJ. Targeted metabolomics of serum acylcarnitines evaluates hepatoprotective effect of wuzhi tablet (schisandra sphenanthera extract) against acute acetaminophen toxicity. Evid Based Complement Alternat Med. 2013;2013:985257.
  • Mutlib AE, Goosen TC, Bauman JN, Williams JA, Kulkarni S.Kostrubsky S. Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity. Chem Res Toxicol. 2006;19:701-9.
  • Hinson JA, Reid AB, McCullough SS.James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev. 2004;36:805-22.
  • Wang ZZ, Zhao WJ, Zhang XS, Tian XF, Wang YZ, Zhang F et al. Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver. World J Gastroenterol. 2007;13:564-71.
  • Sandilands EA.Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009;47:81-8.
There are 33 citations in total.

Details

Primary Language English
Subjects Histology and Embryology
Journal Section Research
Authors

Serdar Yiğit 0000-0001-5631-2335

Tuba Aydın 0000-0002-7653-6480

Soner Bitiktaş 0000-0002-6040-3771

Seyit Ali Bingöl 0000-0001-6422-9582

Muhammed Yayla This is me 0000-0002-0659-3084

Lale Duysak 0000-0001-7872-3880

İsa Yeşilyurt 0000-0002-2164-4580

Ali Alper Kahraman 0000-0003-2924-2655

Publication Date March 29, 2024
Submission Date December 1, 2023
Acceptance Date March 8, 2024
Published in Issue Year 2024 Volume: 49 Issue: 1

Cite

MLA Yiğit, Serdar et al. “Protective Effects of Jervine Purified from Veratrum Album on Paracetamol-Induced Liver Toxicity in Rats”. Cukurova Medical Journal, vol. 49, no. 1, 2024, pp. 150-8, doi:10.17826/cumj.1398401.