ACTIVITY OF RESPIRATORY CHAIN ENZYMES IN THE LIVER OF RATS WITH ACETAMINOPHEN-INDUCED TOXICITY TREATED WITH HERICIUM ALPESTRE ETHANOLIC EXTRACT
DOI:
https://doi.org/10.31861/biosystems2025.03.326Keywords:
acetaminophen, liver, Hericium alpestre ethanolic extract, oxidative stress markers, NADH dehydrogenase, succinate dehydrogenaseAbstract
The study is devoted to determining the liver status indicators under conditions of acetaminophen intoxication and administration of ethanol extract of the mushroom Hericium alpestre. The research was conducted on 4 groups of animals: K – control rats; TІ – rats with modeled toxic injury; EGA – rats administered per os a 20% ethanolic extract of Hericium alpestre fruiting bodies at a dose of 200 µg/kg body weight for 10 days; EGA+TІ – rats administered per os the 20% Hericium alpestre extract for 10 days prior to modeling the acetaminophen-induced injury. It was established that an overdose of acetaminophen is accompanied by the development of pronounced oxidative stress in the liver tissue, as evidenced by an increase in the generation of superoxide anion radical (O2•−) by almost 2.5 times, and hydroxyl radical (HO•) – by 1.7 times compared to the control. The increased production of reactive oxygen species is accompanied by the accumulation of free radical damage products of lipids and proteins, in particular TBA-active products and carbonyl derivatives, as well as a significant inhibition of the activity of NADH dehydrogenase (complex I) and succinate dehydrogenase (complex II) of the mitochondrial respiratory chain. It has been shown that the preliminary administration of ethanol extract of Hericium alpestre before modeling toxic damage with acetaminophen leads to a decrease in the intensity of superoxide generation, and the level of hydroxyl radicals approaches control values. At the same time, animals of this group have a significant decrease in the content of TBA-active products and carbonyl derivatives, as well as an increase in the activity of NADH dehydrogenase and succinate dehydrogenase compared to animals with acetaminophen-induced intoxication that did not receive the extract. The results obtained indicate that the ethanol extract of the mushroom Hericium alpestre exhibits a pronounced antioxidant effect and reduces the manifestations of oxidative damage to the main macromolecules of liver cells, contributing to the partial restoration of mitochondrial function under conditions of acetaminophen overdose.
References
1. Akakpo, J.Y., Olivos, H., Shrestha, B., Midey, A., Jaeschke, H., Ramachandran A. (2024) Spatial analysis of renal acetaminophen metabolism and its modulation by 4-methylpyrazole with DESI mass spectrometry imaging. Toxicol Sci, 198 (2), 328-346. https://doi.org/10.1093/toxsci/kfae011
2. Chong, S., Fung, M.L., Wong, K.H., Lim, L.W. (2020) Therapeutic potential of Hericium erinaceus for depressive disorder. Int J Mol Sci, 21, 163. 10.3390/ijms21010163
3. Gao, Y., Cao, Z., Yang, X., Abdelmegeed, M.A., Sun, J., Chen, S., …Yu, L.R. (2017) Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury. Proteomics Clin Appl, 11 (1-2), 1-29. https://doi.org/10.1002/prca.201600123.
4. Gonkhom, D., Luangharn, T., Raghoonundon, B., Hyde, K., Stadler, M., Thongklang, N. (2021) Hericium: A review of the cultivation, health-enhancing applications, economic importance, industrial, and pharmaceutical applications. Fung Biot, 1 (2), 117-129. 10.5943/FunBiotec/1/2/8.
5. Haidara, M.A., Al-Hashem, F., El Karib, A.O., Zaki, M.S., Kamar, S.S., El-Bidawy, M.H., Al-Ani, B. (2019) Inhibition of paracetamol-induced acute kidney damage in rats using a combination of resveratrol and quercetin. Int. J. Morphol, 37 (4), 1422-1428.
https://doi.org/10.3390/ijms25115949
6. Ito, F., Sono, Y., Ito, T. (2019) Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants (Basel, Switzerland), 8 (3), 72. https://doi.org/10.3390/antiox8030072
7. Jaeschke, H., Ramachandran, A. (2024) Ferroptosis and Intrinsic Drug-induced Liver Injury by Acetaminophen and Other Drugs: A Critical Evaluation and Historical Perspective. J Clin Transl Hepatol, 12(12), 1057-1066. https://doi.org/10.14218/JCTH.2024.00324.
8. Kopylchuk, G.P., Voloshchuk, О.М. (2015) NADH:ubiquinone reductase and succinate dehydrogenase activity in the liver of rats with acetaminopheninduced toxic hepatitis on the background of alimentary protein deficiency The Ukrainian biochemical journal, 87 (1), 121-126. https://doi.org/10.15407/ubj87.01.127
9. Kostanda, E.; Musa, S.; Pereman, I. (2024) Unveiling the Chemical Composition and Biofunctionality of Hericium spp. Fungi: A Comprehensive Overview. Int J Mol Sci, 25, 5949. https://doi.org/10.3390/ijms25115949
10. Kostenko, V.O., Tsebrzhins'kii, O.I. (2000) Production of superoxide anion radical and nitric oxide in renal tissues sutured with different surgical suture material. Fiziol Zh, 46 (5), 56-62. [Ukrainian]
11. Marchenko M. M., Kopyl’chuk G. P., Voloshсhuk O. M. (2011) Energy-producing enzymes activity of Guerin’s carcinoma, transplanted on the low doses irradiation background. Doklady NAN Ukrainy, (1), 153-156. [Ukrainian].
12. Parihar, M.S., Pandit, M.K. (2003) Free radical induced increase in protein carbonyl is attenuated by low doses of adenosine in hippocampus and mid brain: implication in neurodegenerative disorders. Gen Physiol Biophys, 22 (1), 29-39.
13. Purdel NC., Margina D., Ilie M. (2014) Current methods used in the protein carbonyl assay. Ann Res Rev Biol, 4 (12), 2015-2026. https://doi.org/10.9734/ARRB/2014/8763
14. Rodrigues, T., de França, L.P., Kawai, C., de Faria, P.A., Mugnol, K.C., …Nantes, I.L. (2007) Protective role of mitochondrial unsaturated lipids on the preservation of the apoptotic ability of cytochrome C exposed to singlet oxygen. J Biol Chem, 282 (35), 25577-87. doi: 10.1074/jbc.M700009200
15. Tkachenko, M.M., Sahach, V.F., Baziliuk, O.V., Kotsiuruba, A.V., Popereka, H.M., Stepanenko, L.H., Seniuk, O.F. (2005) Age-related characteristics of contractile vascular reactions and the content of oxygen free radicals and nitric oxide metabolites in BALB/c mice in conditions of alienation zone. Fiziol Zh, 51 (3), 32-41. [Ukrainian].
16. Yan, M, Huo, Y, Yin, S, Hu, H. (2018) Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions. Redox Biol. 17, 274-283. https://doi.org/10.1016/j.redox.2018.04.019
