The Influence of Celtis occidentalis L. Extract on Acetaminophen-Induced Nephrotoxicity by Mitigating Inflammation, Oxidative Stress, and Nephrotoxic Nephritis in Rabbits
C. occidentalis Extract Mitigates Nephrotoxicity
DOI:
https://doi.org/10.61919/jhrr.v4i3.1514Keywords:
C. occidentalis, antioxidant enzymes, inflammation, cytokines, oxidative stress, nephrotoxic nephritis, renal histopathology.Abstract
Background: Paracetamol is a commonly available drug used as an analgesic and antipyretic. With or without a prescription, overdose can lead to severe complications such as hepatotoxicity, nephrotoxicity, and acute pancreatitis.
Objective: This research aims to assess the antioxidant, anti-inflammatory, and renoprotective effects of the methanolic extract (met. ext.) of Celtis occidentalis leaves on paracetamol-induced nephrotoxicity in rabbits.
Methods: Forty male rabbits (Oryctolagus cuniculus) were divided into eight groups, each comprising five individuals (n = 5). Groups I, II, III, IV, V, VI, VII, and VIII are the control, paracetamol (PCM) (2 g/kg), met. ext. (200 mg/kg), PCM (2 g/kg) + silymarin (50 mg/kg), silymarin (50 mg/kg), PCM (2 g/kg) + met. ext. (100 mg/kg), PCM (2 g/kg) + met. ext. (200 mg/kg), and PCM (2 g/kg) + met. ext. (300 mg/kg) groups, respectively. These elements were administered orally once a day after 12 hours of fasting. All animals were dissected after 21 days of experimentation.
Results: Results demonstrate that paracetamol overdoses elevated the serum levels of creatinine, urea, and uric acid, caused oxidative stress by increasing the malondialdehyde (MDA) level, and decreased the antioxidant enzyme concentrations (total glutathione and superoxide dismutase). A significant decline in serum biomarkers was observed when treated with the met. ext. of C. occidentalis leaves as compared to the PCM group. The met. ext. of C. occidentalis leaves attenuated oxidative stress by decreasing MDA levels and enhancing antioxidant enzyme levels. It also ameliorated inflammation by decreasing the cytokine levels (IFN-γ and TNF-α). Paracetamol caused dramatic changes in renal histology, including inflammatory cell infiltration, degeneration of the tubular epithelium, glomerular congestion, and parenchymal tissue hemorrhage. These alterations were mitigated by C. occidentalis, as found in the control group.
Conclusion: These findings suggest that C. occidentalis has strong nephroprotective potential, primarily enhancing the antioxidant defense system and reducing inflammatory and oxidative stress in the kidney. However, further research and clinical trials are needed to identify various active compounds for testing in future studies.
Downloads
References
Hussein RM, Kandeil MA, Mohammed NA, Khallaf RA. Evaluation of the Hepatoprotective Effect of Curcumin-Loaded Solid Lipid Nanoparticles Against Paracetamol Overdose Toxicity: Role of Inducible Nitric Oxide Synthase. J Liposome Res. 2022;32(4):365-75.
Thanacoody HR. Large Paracetamol Overdose–Higher Dose NAC Is Not Required. Br J Clin Pharmacol. 2023;89(1):39-42.
Topal I, Özdamar MY, Catakli T, Malkoc İ, Hacimuftuoglu A, Mamoulakis C, Tsatsakis A, Tsarouhas K, Tsitsimpikou C, Taghizadehghalehjoughi A. Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence From an Animal Model. J Clin Med. 2023;12(3):876.
Motawi TK, Ahmed SA, El-Boghdady NA, Metwally NS, Nasr NN. Impact of Betanin Against Paracetamol and Diclofenac Induced Hepato-Renal Damage in Rats. Biomarkers. 2020;25(1):86-93.
Willey JZ, Moon YP, Husain SA, Elkind MS, Sacco RL, Wolf M, Cheung K, Wright CB, Mohan S. Creatinine Versus Cystatin C for Renal Function-Based Mortality Prediction in an Elderly Cohort: The Northern Manhattan Study. PLoS One. 2020;15(1).
Glodny B, Unterholzner V, Taferner B, Hofmann KJ, Rehder P, Strasak A, Petersen J. Normal Kidney Size and Its Influencing Factors—A 64-Slice MDCT Study of 1,040 Asymptomatic Patients. BMC Urol. 2009;9:1-13.
Mescher LA. Junqueira’s Basic Histology. New York: McGraw-Hill; 2016.
Draczevski L, Teixeira ML. Avaliação Do Perfil Bioquímico e Parâmetros Hematológicos em Pacientes Submetidos à Hemodiálise. Saúde Pesq. 2011;4(1):1-10.
Chielle EO, Rigon KA, Arcari IA, Stein V, Santos GA. Influence of Hemodialysis on the Plasma Concentration of Adenosine Deaminase in Patients With Chronic Kidney Disease. J Bras Patol Med Lab. 2015;51:153-57.
Eraky SM, El-Magd NFA. Omega-3 Fatty Acids Protect Against Acetaminophen-Induced Hepatic and Renal Toxicity in Rats Through HO-1-Nrf2-BACH1 Pathway. Arch Biochem Biophys. 2020;687:108387.
Martins JL, Rodrigues OR, de Sousa FB, Fajemiroye JO, Galdino PM, Florentino IF, Costa EA. Medicinal Species With Gastroprotective Activity Found in the Brazilian Cerrado. Fundam Clin Pharmacol. 2015;29(3):238-51.
Wagner C, De Gezelle J, Komarnytsky S. Celtic Provenance in Traditional Herbal Medicine of Medieval Wales and Classical Antiquity. Front Pharmacol. 2020;11:105.
Moerman DE. Native American Ethnobotany. Portland: Timber Press; 1998.
Al-Amarat W, Abukhalil MH, Althunibat OY, Alfwuaires MA, Alnamshan MM, Alqosaibi AI, Ahmed AF, Kamel EM, Arab HH, Mahmoud AM. Galangin Attenuates Liver Injury, Oxidative Stress and Inflammation, and Upregulates Nrf2/HO-1 Signaling in Streptozotocin-Induced Diabetic Rats. Processes. 2021;9(9):1562.
Hozhabri Y, Sadeghi A, Nazari-Robati M, Bahri F, Salimi F, Abolhassani M, Mohammadi A. Effects of Trehalose on NFE2L2, Catalase, and Superoxide Dismutase in the Kidney of Aged Rats. Mol Biol Res Commun. 2022;11(1):29-38.
Lin A, Liu Q, Zhang Y, Wang Q, Li S, Zhu B, Miao L, Du Y, Zhao S, Wei H. A Dopamine-Enabled Universal Assay for Catalase and Catalase-Like Nanozymes. Anal Chem. 2022;94(30):10636-42.
Suvarna KS, Layton C, Bancroft JD. Bancroft's Theory and Practice of Histological Techniques. 8th ed. Elsevier Health Sciences; 2018.
Kara AV, Aldemir MN, Ozcicek F, Mammadov R, Yazici GN, Sunar M, Gulaboglu M. Protective Effect of Taxifolin on Cisplatin-Induced Nephrotoxicity in Rats. Anal Quant Cytopathol Histpathol. 2019;41:47-54.
Pedre B, Barayeu U, Ezeriņa D, Dick TP. The Mechanism of Action of N-Acetylcysteine (NAC): The Emerging Role of H2S and Sulfane Sulfur Species. Pharmacol Ther. 2021;228:107916.
Alhoshani AR, Hafez MM, Husain S, Al-Sheikh AM, Alotaibi MR, Al Rejaie SS, Alshammari MA, Almutairi MM, Al-Shabanah OA. Protective Effect of Rutin Supplementation Against Cisplatin-Induced Nephrotoxicity in Rats. BMC Nephrol. 2017;18:1-10.
Chinnappan SM, George A, Thaggikuppe P, Choudhary Y, Choudhary VK, Ramani Y, Dewangan R. Nephroprotective Effect of Herbal Extract Eurycoma Longifolia on Paracetamol-Induced Nephrotoxicity in Rats. Evid Based Complement Alternat Med. 2019;2019:1-9.
Alanezi AA, Almuqati AF, Alfwuaires MA, Alasmari F, Namazi NI, Althunibat OY, Mahmoud AM. Taxifolin Prevents Cisplatin Nephrotoxicity by Modulating Nrf2/HO-1 Pathway and Mitigating Oxidative Stress and Inflammation in Mice. Pharmaceuticals. 2022;15(11):1310.
Nazir N, Muhammad J, Ghaffar R, Nisar M, Zahoor M, Uddin F, Ullah R, Alotaibi A. Phytochemical Profiling and Antioxidant Potential of Daphne Mucronata Royle and Action Against Paracetamol-Induced Hepatotoxicity and Nephrotoxicity in Rabbits. Saudi J Biol Sci. 2021;28(9):5290-301.
Naz D, Muhamad A, Zeb A, Shah I. In Vitro and In Vivo Antidiabetic Properties of Phenolic Antioxidants From Sedum Adenotrichum. Front Nutr. 2019;6:177.
Naz D, Zeb A, Nazir N, Ullah R, Rahman AU, Muhammad A. Hepatoprotective and Nephroprotective Effects of Sedum Adenotrichum in Paracetamol-Induced Hepatotoxicity in Rabbits. 3 Biotech. 2023;13(6):217.
Ahmad S, Zeb A. Nephroprotective Property of Trifolium Repens Leaf Extract Against Paracetamol-Induced Kidney Damage in Mice. 3 Biotech. 2020;10(12):541.
Fadil HA, Behairy A, Ebraheim LL, Abd-Elhakim YM, Fathy HH. The Palliative Effect of Mulberry Leaf and Olive Leaf Ethanolic Extracts on Hepatic CYP2E1 and Caspase-3 Immunoexpression and Oxidative Damage Induced by Paracetamol in Male Rats. Environ Sci Pollut Res. 2023;30(14):41682-99.
Focak M, Suljevic D. Ameliorative Effects of Propolis and Royal Jelly Against CCl4-Induced Hepatotoxicity and Nephrotoxicity in Wistar Rats. Chemistry Biodivers. 2023;20(1).
Singh DP, Mani D. Protective Effect of Triphala Rasayana Against Paracetamol-Induced Hepato-Renal Toxicity in Mice. J Ayurveda Integr Med. 2015;6(3):181-88.
Abraham P. Oxidative Stress in Paracetamol-Induced Pathogenesis: (I) Renal Damage. Kidney Int. 2005;55:1945-51.
Dahlin DC, Miwa GT, Lu AY, Nelson SD. N-Acetyl-P-Benzoquinone Imine: A Cytochrome P-450-Mediated Oxidation Product of Acetaminophen. Proc Natl Acad Sci USA. 1984;81(5):1327-31.
Manimaran A, Sarkar SN, Sankar P. Influence of Repeated Preexposure to Arsenic on Acetaminophen-Induced Oxidative Stress in the Liver of Male Rats. Food Chem Toxicol. 2010;48(2):605-10.
Sharma S, Chaturvedi J, Chaudhari BP, Singh RL, Kakkar P. Probiotic Enterococcus Lactis IITRHR1 Protects Against Acetaminophen-Induced Hepatotoxicity. Nutrition. 2012;28(2):173-81.
da Silva Melo DA, Saciura VC, Poloni JA, Oliveira CS, Alves Filho JC, Padilha RZ, Reichel CL, Neto EJ, Oliveira RM, D'avila LC, Kessler A. Evaluation of Renal Enzymuria and Cellular Excretion as a Marker of Acute Nephrotoxicity Due to an Overdose of Paracetamol in Wistar Rats. Clin Chim Acta. 2006;373(1-2):88-91.
Neto JA, Oliveira-Filho RM, Simoes MJ, Soares JM, Kulay L. Long-Term Acetaminophen (Paracetamol) Treatment Causes Liver and Kidney Ultra-Structural Changes During Rat Pregnancy. Clin Exp Obstet Gynecol. 2004;31(3):221-24.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Abdul Muhsin Muhsin, Dil Naz, Sawaira Nazir, Sahar Gul, Shahdiar Khan, Abdul Aziz Mian, Waqas Ahmad, Rizwanullah
This work is licensed under a Creative Commons Attribution 4.0 International License.