Повреждения печени и почек у мышей, вызванные ацетаминофеном: лечение корневищем Alpinia officinarum

Парацетамол (ацетаминофен) широко используется во всем мире в качестве анальгетика и жаропонижающего средства. Он эффективен и безопасен при приеме в терапевтических дозах, однако его передозировка может привести к токсическому поражению печени и почек как у людей, так и у животных. Лекарственные растения являются важным компонентом в рационе питания человека, а также активно применяются в области здравоохранения, и многие из них обладают защитным эффектом от повреждений печени и почек. Данное исследование направлено на изучение защитных эффектов различных экстрактов Alpinia officinarum (галангал, I) для печени и почек у мышей, подвергшихся воздействию ацетаминофена. В частности, в ходе работы изучено влияние экстрактов, полученных с помощью различных растворителей, включая полярные, неполярные органические растворители и водные растворы. Результаты исследования показали, что эфирные масла, этанольные и хлороформенные экстракты оказывают наиболее выраженное защитное влияние на печень и почки. Это защитное влияние может быть обусловлено наличием флавоноидов, алкалоидов, терпеноидов, жирных кислот и фитостеролов в указанных экстрактах. В заключение следует отметить, что эфирное масло, этанол и хлороформ, использованные для экстракции корневища галангала, эффективно изолировали различные биоактивные компоненты, что обеспечило существенную защиту от поражения печени и почек, вызванного парацетамолом у мышей.

1. Kaplowitz N. Drug-induced liver disorders: implications for drug development and regulation. Drug Safety. 2001;24:483-490. DOI: 10.2165/00002018-200124070-00001.

2. Maddrey W. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. Gastroenterology. 2000;118(5):984-985. DOI: 10.1016/S0016-5085(00)70192-2.

3. Kaplowitz N. Drug-induced liver injury. Clinical Infectious Diseases. 2004;38(sup.2):S44-S48. DOI: 10.1086/381446.

4. Perazella M.A. Pharmacology behind common drug nephrotoxicities. Clinical Journal of the American Society of Nephrology. 2018;13(12):1897-1908. DOI: 10.2215/cjn.00150118.

5. Stern S.T., Bruno M.K., Hennig G.E., Horton R.A., Roberts J.C., Cohen S.D. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity in CD-1 mice: I. Enhancement of acetaminophen nephrotoxicity by acetaminophen-cysteine. Toxicology and Applied Pharmacology. 2005;202(2):151-159. DOI: 10.1016/j.taap.2004.06.030.

6. Jaeschke H., Bajt M.L. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicological Sciences. 2006;89(1):31-41. DOI: 10.1093/toxsci/kfi336.

7. He M., Zhang S., Jiao Y., Lin X., Huang J., Chen C., et al. Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice. Food and Chemical Toxicology. 2012;50(9):3142-3149. DOI: 10.1016/j.fct.2012.06.020.

8. Gao C., Liu C., Chen Y., Wang Q., Hao Z. Protective effects of natural products against drug-induced nephrotoxicity: a review in recent years. Food and Chemical Toxicology. 2021;153:112255. DOI: 10.1016/j.fct.2021.112255.

9. Liao J., Lu Q., Li Z., Li J., Zhao Q., Li J. Acetaminophen-induced liver injury: molecular mechanism and treatments from natural products. Frontiers in Pharmacology. 2023;14:1122632. DOI: 10.3389/fphar.2023.1122632.

10. Ding P., Yang L., Feng C., Xian J. Research and application of Alpinia officinarum in medicinal field. Chinese Herbal Medicines. 2019;11(2):132-140. DOI: 10.1016/j.chmed.2019.04.003.

11. Ahmed M., Riaz S., Ahmad A., Farooq R., Mubeen U., Hussain M., et al. Alpinia officinarum (Galangal): a beneficial plant. Journal of Medicine and Public Health. 2023;4(1):1057.

12. Amraoui W., Adjabi N., Bououza F., Boumendjel M., Taibi F., Boumendjel A., et al. Modulatory role of selenium and vitamin E, natural antioxidants, against bisphenol a-induced oxidative stress in Wistar albinos rats. Toxicological Research. 2018;34:231-239. DOI: 10.5487/tr.2018.34.3.231.

13. Zuo X., Gao L., Peng X., Dong L., Huang M., Hu T., et al. Unveiling the role of mtDNA in Liver-Kidney Crosstalk: insights from trichloroethylene hypersensitivity syndrome. International Immunopharmacology. 2024;138:112513. DOI: 10.1016/j.intimp.2024.112513.

14. An Q., Ren J.-N., Li X., Fan G., Qu S.-S., Song Y., et al. Recent updates on bioactive properties of linalool. Food & Function. 2021;12(21):10370-10389. DOI: 10.1039/D1FO02120F.

15. Ahmadi A., Khalili M., Margedari S., Nahri-Niknafs B. Antidiabetic and antilipidemic effects of some polar and nonpolar extracts of Securigera securidaca flowers. Pharmaceutical Chemistry Journal. 2016;49:753-759. DOI: 10.1007/s11094-016-1365-6.

16. Ahmadi A., Khalili M., Mashaee F., Nahri-Niknafs B. The effects of solvent polarity on hypoglycemic and hypolipidemic activities of Vaccinium arctostaphylos L. unripe fruits. Pharmaceutical Chemistry Journal. 2017;50:746-752. DOI: 10.1007/s11094-017-1524-4.

17. Ahmadi A., Khalili M., Roghani A., Behi A., Nazirzadeh S. The effects of solvent polarity on hypoglycemic and hypolipidemic activities of Portulaca oleracea and Achillea eriophora DC extracts. Pharmaceutical Chemistry Journal. 2021;54:1243-1254. DOI: 10.1007/s11094-021-02350-y.

18. Ahmadi A., Roghani M., Parsianfard M., Seyedmomeni F., Gheraati S., Sobhanian S.A. Antihyperglycemic and antihyperlipidemic evaluation of Zingiber officinale, Anethum graveolens and Citrullus colocynthis extracts with different polarities in streptozotocin-induced diabetic rats. Pharmaceutical Chemistry Journal. 2022;55:1062-1070. DOI: 10.1007/s11094-021-02538-2.

19. Zheng H., Zhao J., Zheng Y., Wu J., Liu Y., Peng J., et al. Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non-alcoholic fatty liver disease in rats. Molecular Medicine Reports. 2014;10(4):1758-1764. DOI: 10.3892/mmr.2014.2403.

20. Rui Y., Li S., Luan F., Li D., Liu R., Zeng N. Several alkaloids in Chinese herbal medicine exert protection in acute kidney injury: focus on mechanism and target analysis. Oxidative Medicine and Cellular Longevity. 2022:2427802. DOI: 10.1155/2022/2427802

21. Faria J., Ahmed S., Gerritsen K.G.F., Mihaila S.M., Masereeuw R. Kidney-based in vitro models for drug-induced toxicity testing. Archives of Toxicology. 2019;93:3397-3418. DOI: 10.1007/s00204-019-02598-0.

22. Downes K.J., Hayes M., Fitzgerald J.C., Pais G.M., Liu J., Zane N.R., et al. Mechanisms of antimicrobial-induced nephrotoxicity in children. Journal of Antimicrobial Chemotherapy. 2020;75(1):1-13. DOI: 10.1093/jac/dkz325.

23. Svenia P.J., Asha S., Krishnakumar I.M., Ratheesh M., Savitha S., Sandya S., et al. Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers. Biomedicine & Pharmacotherapy. 2017;85:128-135. DOI: 10.1016/j.biopha.2016.11.117.

24. Xiang H., Song Y., Wang Y., Fu W., Xiao N. A novel NIR fluorescent probe for in situ visualizing Fe(II) and its application in drug-induced liver/kidney injury. Materials Advances. 2024;5(13):5624-5631. DOI: 10.1039/d4ma00361f.

25. Akakpo J.Y., Ramachandran A., Orhan H., Curry S.C., Rumack B.H., Jaeschke H. 4-Methylpyrazole protects against acetaminophen-induced acute kidney injury. Toxicology and Applied Pharmacology. 2020;409:115317. DOI: 10.1016/j.taap.2020.115317.

26. Zeng X., Chen J., Yu S., Liu Z., Ma M. A highly selective and sensitive “turn-on” fluorescent probe for Fe 2+ and its applications. Journal of Luminescence. 2022;250:119069. DOI: 10.1016/j.jlumin.2022.119069.

27. Wu L., Liu J., Tian X., Groleau R.R., Bull S.D., Li P., et al. Fluorescent probe for the imaging of superoxide and peroxynitrite during drug-induced liver injury. Chemical Science. 2021;12(11):3921-3928. DOI: 10.1039/d0sc05937d.

28. Guengerich F.P. Cytochrome P450 2E1 and its roles in disease. Chemico-Biological Interactions. 2020;322:109056. DOI: 10.1016/j.cbi.2020.109056.

29. Begriche K., Penhoat C., Bernabeu-Gentey P., Massart J., Fromenty B. Acetaminophen-induced hepatotoxicity in obesity and nonalcoholic fatty liver disease: a critical review. Livers. 2023;3(1):33-53. DOI: 10.3390/livers3010003.

30. Kalsi S.S., Wood D.M., Waring W.S., Dargan P.I. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose? Open Access Emergency Medicine. 2011;3:69-76. DOI: 10.2147/oaem.S24962.

31. Marto N., Morello J., Antunes A.M.M., Azeredo S., Monteiro E.C., Pereira S.A. A simple method to measure sulfonation in man using paracetamol as probe drug. Scientific Reports. 2021;11:9036. DOI: 10.1038/s41598-021-88393-3.

32. Sharifi-Rigi A., Heidarian E., Amini S.A. Protective and anti-inflammatory effects of hydroalcoholic leaf extract of Origanum vulgare on oxidative stress, TNF-α gene expression and liver histological changes in paraquat-induced hepatotoxicity in rats. Archives of Physiology and Biochemistry. 2018;125(1):56-63. DOI: 10.1080/13813455.2018.1437186.

33. Park C.H., Lee A.Y., Kim J.H., Seong S.H., Jang G.Y., Cho E.J., et al. Protective effect of safflower seed on cisplatin-induced renal damage in mice via oxidative stress and apoptosis-mediated pathways. The American Journal of Chinese Medicine. 2018;46(1):157-174. DOI: 10.1142/s0192415x1850009x.

34. Panche A.N., Diwan A.D., Chandra S.R. Flavonoids: an overview. Journal of Nutritional Science. 2016;5:e47. DOI: 10.1017/jns.2016.41.

35. Tsai M.S., Chien C.C., Lin T.H., Liu C.-C., Liu R.H., Su H.-L., et al. Galangin prevents acute hepatorenal toxicity in novel propacetamol-induced acetaminophen-overdosed mice. Journal of Medicinal Food. 2015;18(11):1187-1197. DOI: 10.1089/jmf.2014.3328.

36. Zhu J., Wang Q., Li H., Zhang H., Zhu Y., Omari-Siaw E., et al. Galangin-loaded, liver targeting liposomes: optimization and hepatoprotective efficacy. Journal of Drug Delivery Science and Technology. 2018;46:339-347. DOI: 10.1016/j.jddst.2018.05.034.

37. Huang Y.-C., Tsai M.-S., Hsieh P.-C., Shih J.-H., Wang T.-S., Wang Y.-C., et al. Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. Toxicology and Applied Pharmacology. 2017;329:128-139. DOI: 10.1016/j.taap.2017.05.034.

38. Alruhaimi R.S., Ahmeda A.F., Hussein O.E., Alotaibi M.F., Germoush M.O., Elgebaly H.A., et al. Galangin attenuates chlorpyrifos-induced kidney injury by mitigating oxidative stress and inflammation and upregulating Nrf2 and farnesoid-X-receptor in rats. Environmental Toxicology and Pharmacology. 2024;110:104542. DOI: 10.1016/j.etap.2024.104542.