Study the Effect of the Combination of Flavonoids of the Crocus Sativus Plant on Opportunistic Intestinal Microorganisms Against the Background of Acute Toxic Hepatitis Caused in Mice Under Study Conditions
Keywords:
Bacterial infections, acute paracetamol hepatitis, antibiotic resistance, Crocus sativus, Karsil, ciprofloxacinAbstract
Not only infectious factors, but also the expanding scale of industrial production today increase the occurrence of liver diseases against the background of the adverse effects of the production process or manufactured artificial synthetic substances, medicines on many human organs and systems. On the other hand, emerging liver diseases themselves cause serious medical, social and even economic problems due to the development of complications that cause disability and death, such as hepatocellular carcinoma or fibrosis and cirrhosis of the liver. The appearance of antibiotic-resistant strains used to prevent secondary infection during the improvement of antiviral or hepatoprotective agents for the treatment of liver diseases causes a decrease in the effectiveness of treatment. In this regard, the priority task is to determine the effectiveness of drugs with high hepatoprotective activity obtained on a plant basis, namely when using antibiotics. To this end, simultaneous activity against hepatoprotective and intestinal pathogenic strains against the background of acute toxic hepatitis was detected in laboratory white mice of Crocus savitus plant extract. Acute toxic hepatitis was caused in white mice by oral administration of a paracetamol solution (JSC Pharmstandard-Lexredstva Russia) at a dose of 1500 mg/kg once 2 times in a row. The solution of the studied plant extract was selected as a comparative drug together with ciprofloxacin 50 mg/kg in dose of 50 mg/kg using a special atraumatic probe from 3 days of the study, the drug Karsil was administered orally to white mice at a dose of 50 mg/kg together with ciprofloxacin 50 mg/kg for 14 days. And the control group was given distilled water corresponding to the volume of the test substance. In the experiments conducted, it was found that the studied plant extract not only exhibits high hepatoprotective activity, but also eliminates cases of dysbiosis, which can develop under the action of ciprofloxacin.
References
Roth, G.A.; Abate, D.; Abate, K.H.; Abay, S.M.; Abbafati, C.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdela, J.; Abdelalim, A.; et al. Global, Regional, and National Age-Sex-Specific Mortality for 282 Causes of Death in 195 Countries and Territories, 1980–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet 2018, 392, 1736–1788. https://doi.org/10.1016/S0140-6736(18)32203-7
GBD 2017 Cirrhosis Collaborators The Global, Regional, and National Burden of Cirrhosis by Cause in 195 Countries and Territories, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020, 5, 245–266.
https://doi.org/10.1016/S2468-1253(19)30349-8
Aniemeka, C., Pillai, A.A. HCC Mortality Trends—In with ALD (and NAFLD) and Out with HCV. Dig Dis Sci 67, 3483-3484 (2022). https://doi.org/10.1007/s10620-022-07434-7
Gong L, Wei F, Gonzalez FJ, Li G. Hepatic fibrosis: targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines. Hepatology. 2023 Jan 3. doi:
1097/HEP.0000000000000182
Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021;18:151-166. https://doi.org/10.1038/s41575-020-00372-7
Campana L, Esser H, Huch M, Forbes S. Liver regeneration and inflammation: from fundamental science to clinical applications. Nat Rev Mol Cell Biol. 2021;22:608-624.
https://doi.org/10.1038/s41580-021-00373-7
Asrani S.K., Devarbhavi H., Eaton J., Kamath P.S. Burden of liver diseases in the world. J. Hepatol. 2019;70:151–171. https://doi.org/10.1016/j.jhep.2018.09.014
Moon, A.M.; Singal, A.G.; Tapper, E.B. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clin. Gastroenterol. Hepatol. 2020, 18, 2650–2666.
https: //doi.org/10.1016/j.cgh.2019.07.060
Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022; 28(41): 5910-5930 [PMID: 36405106 DOI: 10.3748/wjg.v28.i41.5910
Taylor, R.S.; Taylor, R.J.; Bayliss, S.; Hagström, H.; Nasr, P.; Schattenberg, J.M.; Ishigami, M.; Toyoda, H.; Wai-Sun Wong, V.; Peleg, N.; et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020, 158, 1611–1625.e12.
https: //doi.org/10.1053/j.gastro.2020.01.043
Bertuccio P, Turati F, Carioli G et al. Global trends and predictions in HCC mortality. J Hepatol. 2017;67:302–309. DOI: https://doi.org/10.1016/j.jhep.2017.03.011
Cholankeril G, Yoo ER, Perumpail RB et al. Rising rates of hepatocellular carcinoma leading to liver transplantation in baby boomer generation with chronic hepatitis C, alcohol liver disease, and nonalcoholic steatohepatitis-related liver disease.
Diseases. 2017;5:20. https://doi.org/10.3390/diseases5040020
Mokdad A.A. Lopez A.D. Shahraz S. Lozano R. Mokdad A.H. Stanaway J. et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. 12 2014; 12: 145. DOI: 10.1186/s12916-014-0145-y
Canivet, C.M.; Boursier, J. Screening for Liver Fibrosis in the General Population: Where Do We Stand in 2022? Diagnostics 2023, 13,91. https://doi.org/10.3390/diagnostics13010091
Mendez-Sanchez N, Coronel-Castillo CE, Cordova-Gallardo J, Qi X. Antibiotics in Chronic Liver Disease and Their Effects on Gut Microbiota. Antibiotics (Basel). 2023 Sep 22;12(10):1475. doi: 10.3390/antibiotics12101475.
Liu XQ, Zhang XY, Ying Y, Zheng JM, Sun J, Zhang WH, Zhang JM, Huang YX. The role of prophylactic antibiotics in hepatitis B virus-related acute-on-chronic liver failure patients at risk of bacterial infection: a retrospective study. Infect Dis Poverty. 2021 Mar 31;10(1):44. doi: 10.1186/s40249-021-00830-7.
Zheng Z., Wang B. The Gut-Liver Axis in Health and Disease: The Role of Gut Microbiota-Derived Signals in Liver Injury and Regeneration. Front. Immunol. 2021;12:775526. doi: 10.3389/fimmu.2021.775526.
Schwenger K.J., Clermont-Dejean N., Allard J.P. The role of the gut microbiome in chronic liver disease: The clinical evidence revised. JHEP Rep. 2019;1:214–226. doi:
1016/j.jhepr.2019.04.004.
Ferrarese A., Passigato N., Cusumano C., Gemini S., Tonon A., Dajti E., Marasco G., Ravaioli F., Colecchia A. Antibiotic prophylaxis in patients with cirrhosis: Current evidence for clinical practice. World J. Hepatol. 2021;13:840–852. doi: 10.4254/wjh.v13.i8.840.
Gao Y., Qian B., Zhang X., Liu H., Han T. Prophylactic antibiotics on patients with cirrhosis and upper gastrointestinal bleeding: A meta-analysis. PLoS ONE. 2022;17:e0279496. doi:
1371/journal.pone.0279496.
National Research Council. 2011. Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC: The National Academies Press. https://doi.org/10.17226/12910.
Экспериментальный лекарственный гепатит. Гепатопротекторные эффекты препарата Лаеннек на моделях токсического повреждения печени парацетамолом или алкоголем / О. А. Громова, И. Ю. Торшин, В. И. Демидов [и др.] // Экспериментальная и клиническая гастроэнтерология. – 2022. – № 3(199). – С. 86–92. – DOI 10.31146/1682–8658-ecg-199-3-86-92. – EDN JWNRVC.
Dalbeni A., Mantovani A., Zoncapè M., Cattazzo F., Bevilacqua M., De Marco L., Paon V., Ieluzzi D., Azzini A.M., Carrara E., et al. The multi-drug resistant organisms infections decrease during the antimicrobial stewardship era in cirrhotic patients: An Italian cohort study. PLoS ONE. 2023;18:e0281813. doi: 10.1371/journal.pone.0281813.
Louvet A., Labreuche J., Dao T., Thévenot T., Oberti F., Bureau C., Paupard T., Nguyen-Khac E., Minello A., Bernard-Chabert B., et al. Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial. JAMA. 2023;329:1558–1566. doi: 10.1001/jama.2023.4902.
Kremer W.M., Gairing S.J., Kaps L., Ismail E., Kalampoka V., Hilscher M., Michel M., Siegel E., Schattenberg J.M., Galle P.R., et al. Characteristics of bacterial infections and prevalence of multidrug-resistant bacteria in hospitalized patients with liver cirrhosis in Germany. Ann. Hepatol. 2022;27:100719. doi: 10.1016/j.aohep.2022.100719.
Fernandez J., Piano S., Bartoletti M., Wey E.Q. Management of bacterial and fungal infections in cirrhosis: The MDRO challenge. J. Hepatol. 2021;75((Suppl. 1)):S101–S117. doi:
1016/j.jhep.2020.11.010.
