Protective Effect of Rumex vesicarius L. Leaf Extract against Paracetamol-Induced Hepatorenal Oxidative Injury in Wistar Rats
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Abstract
Paracetamol overdose-induced hepatic injury continues to be an important problem and may also be associated with clinically significant renal damage through mechanisms that involve formation of reactive metabolites, glutathione depletion, oxidative stress, mitochondrial dysfunction, and secondary inflammatory amplification. This study aimed to evaluate the protective effect of leaf extract of Rumex vesicarius L. against paracetamol-induced oxidative damage to liver and kidneys in normal Wistar rats. This is achieved by integrating pharmacognostic standardization, physiological relevance, and mechanistic pharmacology. A hydroalcoholic leaf extract was evaluated in a rat model of paracetamol toxicity using serum biochemical markers of liver and kidney function, tissue oxidative stress indices, antioxidant enzyme activities, inflammatory cytokines, and histopathological evaluation of both organs. The result showed that paracetamol causes big rises of serum transaminases, alkaline phosphatase, bilirubin, urea, blood urea nitrogen, creatinine, tissue malondialdehyde, and pro-inflammatory cytokines. It also decreased the levels of glutathione and enzymatic antioxidant defenses. The Rumex vesicarius extract decreased these changes in a dose-dependent manner and preserved the hepatic and renal architecture histologically. Collectively, the results support the notion that a leaf extract of R. vesicarius protective profile is due to its ability to cooperate with other antioxidants, anti-inflammatories and tissue-preserving agents.
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References
Jaeschke H., Ramachandran A. (2024). Central mechanisms of acetaminophen hepatotoxicity: mitochondrial dysfunction by protein adducts and oxidant stress. Drug Metabolism and Disposition, 52(8), 712–721. https://doi.org/10.1124/dmd.123.001279
Ramachandran A., Jaeschke H. (2017). Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology. Journal of Clinical and Translational Research, 3(Suppl 1), 157–169. https://doi.org/10.18053/jctres.03.2017S1.002
Du K., Ramachandran A., Jaeschke H. (2016). Oxidative stress during acetaminophen hepatotoxicity: sources, pathophysiological role and therapeutic potential. Redox Biology, 10, 148–156. https://doi.org/10.1016/j.redox.2016.10.001
Yoon E., Babar A., Choudhary M., Kutner M., Pyrsopoulos N. (2016). Acetaminophen-induced hepatotoxicity: a comprehensive update. Journal of Clinical and Translational Hepatology, 4(2), 131–142. https://doi.org/10.14218/JCTH.2015.00052
Akakpo J.Y., Ramachandran A., Orhan H., Curry S.C., Rumack B.H., Jaeschke H. (2020). 4-Methylpyrazole protects against acetaminophen-induced acute kidney injury. Toxicology and Applied Pharmacology, 409, 115317. https://doi.org/10.1016/j.taap.2020.115317
Du K., Xie Y., McGill M.R., Jaeschke H. (2015). Pathophysiological significance of c-jun N-terminal kinase in acetaminophen hepatotoxicity. Expert Opinion on Drug Metabolism & Toxicology, 11(11), 1769–1779. https://doi.org/10.1517/17425255.2015.1071353
Güvenç M., Cellat M., Gökçek İ., Özkan H., Arkalı G., Yakan A., et al. (2020). Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats. Journal of Biochemical and Molecular Toxicology, 34(2), e22427. https://doi.org/10.1002/jbt.22427
Senocak E.A., Utlu N., Kurt S., Kucukler S., Kandemir F.M. (2024). Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis, and inflammatory cytokines in rats. Biological Trace Element Research, 202(3), 1164–1173. https://doi.org/10.1007/s12011-023-03755-4
Khedre E.K.M., Hegab A.M.M., El-Mahis A.A., Abdel Rahman A.A.S., Elwakeel S.H.B., Abdelhameed A.S., et al. (2025). Ziziphus spina-christi alleviates paracetamol-induced hepatorenal toxicity in rats through in vivo and computational approaches. Scientific Reports, 15, 30163. https://doi.org/10.1038/s41598-025-14454-6
Ahmad S.T., Arjumand W., Nafees S., Seth A., Ali N., Rashid S., et al. (2012). Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicology Letters, 208(2), 149–161. https://doi.org/10.1016/j.toxlet.2011.10.023
Zhao Y.L., Zhou G.D., Yang H.B., Wang J.B., Shan L.M., Li R.S., et al. (2011). Rhein protects against acetaminophen-induced hepatic and renal toxicity. Food and Chemical Toxicology, 49(8), 1705–1710. https://doi.org/10.1016/j.fct.2011.04.011
Shin J.Y., Han J.H., Ko J.W., Park S.H., Shin N.R., Jung T.Y., et al. (2016). Diallyl disulfide attenuates acetaminophen-induced renal injury in rats. Laboratory Animal Research, 32(4), 200–207. https://doi.org/10.5625/lar.2016.32.4.200
El-Hawary S.A., Sokkar N.M., Ali Z.Y., Yehia M.M. (2011). A profile of bioactive compounds of Rumex vesicarius L. Journal of Food Science, 76(8), C1195–C1202. https://doi.org/10.1111/j.1750-3841.2011.02370.x
Sweilam S.H., Abd El Hafeez M.S., Mansour M.A., Mekky R.H. (2024). Unravelling the phytochemical composition and antioxidant potential of different parts of Rumex vesicarius L.: a RP-HPLC-MS-MS/MS, chemometrics, and molecular docking-based comparative study. Plants, 13(13), 1815. https://doi.org/10.3390/plants13131815
Gohar M.M., Ezzat S.M., Yeskaliyeva B., Elhawary S.S., Kirollos F.N., Khouchlaa A., et al. (2025). Rumex species: phytochemistry, pharmacology and nutritional potential for food and health applications. Food Science & Nutrition, 13(12), e71300. https://doi.org/10.1002/fsn3.71300
Tukappa N.K.N., Londonkar R.L., Nayaka H.B., Kumar C.B.S. (2015). Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex vesicarius L. Biological Research, 48, 19. https://doi.org/10.1186/s40659-015-0009-8
Hasan M.M., Tasmin M.S., El-Shehawi A.M., Elseehy M.M., Reza M.A., Haque A. (2021). R. vesicarius L. exerts nephroprotective effect against cisplatin-induced oxidative stress. BMC Complementary Medicine and Therapies, 21(1), 225. https://doi.org/10.1186/s12906-021-03398-9
Monagas M., Brendler T., Brinckmann J., Dentali S., Gafner S., Giancaspro G., et al. (2022). Understanding plant to extract ratios in botanical extracts. Frontiers in Pharmacology, 13, 981978. https://doi.org/10.3389/fphar.2022.981978
Funk J.L., Schneider C. (2021). Perspective on improving the relevance, rigor, and reproducibility of botanical clinical trials: lessons learned from turmeric trials. Frontiers in Nutrition, 8, 782912. https://doi.org/10.3389/fnut.2021.782912
World Health Organization. (1998). Quality control methods for medicinal plant materials. World Health Organization.
Organisation for Economic Co-operation and Development. (2002). Test No. 423: Acute oral toxicity—acute toxic class method. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing. https://doi.org/10.1787/9789264071001-en
Percie du Sert N., Hurst V., Ahluwalia A., Alam S., Avey M.T., Baker M., et al. (2020). The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. BMC Veterinary Research, 16(1), 242. https://doi.org/10.1186/s12917-020-02451-y
Lancaster E.M., Hiatt J.R., Zarrinpar A. (2015). Acetaminophen hepatotoxicity: an updated review. Archives of Toxicology, 89(2), 193–199. https://doi.org/10.1007/s00204-014-1432-2
Beger R.D., Bhattacharyya S., Yang X., Gill P.S., Schnackenberg L.K., Sun J., et al. (2015). Translational biomarkers of acetaminophen-induced acute liver injury. Archives of Toxicology, 89(9), 1497–1522. https://doi.org/10.1007/s00204-015-1519-4