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Yıl 2022, Cilt: 5 Sayı: 2, 146 - 161, 02.01.2023
https://doi.org/10.38093/cupmap.1167888

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Effect of chronic administration of aqueous extract of Neem (Azadirachta indica) leaves on Paracetamol-induced hepatotoxicity in Wistar albino rats

Yıl 2022, Cilt: 5 Sayı: 2, 146 - 161, 02.01.2023
https://doi.org/10.38093/cupmap.1167888

Öz

Hepatoprotective drugs are not available for use in modern medicine and different parts of medicinal plants like Neem (Azadirachta indica) are used as hepatoprotectants in traditional medicine. Although there are scientific reports of its hepatoprotective activity on acute administration, we found only one study which had evaluated its hepatoprotective effect on chronic administration. Objectives: To evaluate the effect of chronic oral administration of Neem on paracetamol-induced hepatotoxicity in Wistar rats. Methods: We randomly assigned 72 male and female Wistar albino rats to four groups of 18 animals each and orally administered Distilled water 5ml/kg body weight/day to Groups A (Normal control) and B (Experimental control), 500 mg/kg aqueous Neem leaf extract (Test) to Group C and Silymarin suspension (Standard) 100mg/kg/day to Group D for 30 days. On the 8th day, we induced hepatotoxicity with Paracetamol 2g/kg body weight single dose to groups B, C and D. We performed liver function tests, recorded liver weights and examined liver histology of six rats from each group on 10th, 20th and 30th days. Results: We observed significant difference (P<0.05) in Mean ± SEM values of serum bilirubin, ALP, AST, ALT, liver weights, total protein and albumin: globulin in Group B compared to Group A, whereas these changes were significantly less in groups C and D compared to B. Histopathological examination of liver showed hepatic necrosis on 10th day in Groups B, C and D, but on 20th and 30th day in Group B and on 10th day in Groups C and D, we observed decrease in sinusoidal congestion and cloudy swelling along with small areas of regenerative changes. All abnormal histological changes decreased by the 30th day. Conclusion: Thus, aqueous extract of Azadirachta indica leaves shows hepatoprotective activity on chronic oral administration in Wistar rats.

Destekleyen Kurum

Assam Medical College, Dibrugarh, Assam, India

Teşekkür

1. Dibrugarh University, Dibrugarh Assam, India for financial support (dissertation grant) for the study. 2. Dr. Jibon Gogoi, Vice Principal, Institute of Pharmacy and faculty and postgraduates of the department of Pharmacology, Assam Medical College & Hospital, Dibrugarh, Assam, India 3. Laboratory technicians of the departments of Pathology and Biochemistry 4. Laboratory attendants of the Central Animal House and the department of Pharmacology for animal care and handling

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  • Althaiban MA.,(2019). Evaluation of hepatopotective activity of Neem extract in Rifampin induced acute hepatic failure in rats. International Journal of Pharmaceutical Research and Allied Sciences,8(3),29-36
  • Sani, I., Umar, RA., Hassan, SW., Faruq, UZ., Bello, F., and Aminu, H., et al. (2020). Hepatoprotective Effect of Azadirachta indica Leaf Fractionated Extracts against Snake Venom Toxicity on Albino Rats, Saudi Journal of Biomedical Research,5(6),112-117 DOI: 10.36348/sjbr.2020.v05i06.004
  • Seriana, I., Akmal, M., Darusman, D., Wahyuni, S., Khairan, K., and Sugito, S., (2021). Neem Leaf (Azadirachta indica A. Juss) Ethanolic Extract on the Liver and Kidney Function of Rats, Hindawi The Scientific World Journal 2021,Article ID 7970424, 7 pages https://doi.org/10.1155/2021/7970424
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  • Mallick, A., Ghosh, S., Banerjee, S., Majumder, S., Das, A., and Mondal, B., et. al, (2013). Neem leaf glycoprotein is nontoxic to physiological functions of Swiss mice and Sprague Dawley rats: histological, biochemical and immunological perspectives, International Immunopharmacology, Jan,15(1),73-83. doi: 10.1016/j.intimp.2012.11.006. Epub 2012 Nov 21. PMID: 23178577.
  • Suhendro., Susraini, AAAN., Saputra, H., and Sriwidyani, NP.,(2018). Oral administration of neem (Azadirachta indica A. Juss) leaf extract increases Cyclin D1 expression in hepatocyte regeneration in acetaminophen-induced hepatotoxic wistar rats, Bali Medical Journal,7(1),12-16 DOI:10.15562/bmj.v7i1.700
  • Kim, WR., Flamm, SL., Di Bisceglie, AM., and Bodenheimer, HC.,(2008). Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease, Hepatology, Apr,47(4),1363-1370. doi: 10.1002/hep.22109. PMID: 18366115.
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  • Teloh HA., (1978). Serum proteins in hepatic disease, Annals of Clinical & Laboratory Science,8(2),127-129
  • Amacher, DE.,(1998). Serum transaminase elevations as indicators of hepatic injury following the administration of drugs, Regulatory Toxicology and Pharmacology,27,119-130.
  • Raucy, JL., Lasker, JM., Lieber, CS., and Black, M.,(1989). Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2, Archives of Biochemistry and Biophysics, Jun,271(2),270-283. doi: 10.1016/0003-9861(89)90278-6. PMID: 2729995.
  • James, LP., Mayeux, PR., and Hinson, JA.,(2003). Acetaminophen-induced hepatotoxicity. Drug Metabolism and Disposition, 31,1499 -1506.
  • Moore, M., Thor, H., Moore, G., Nelson, S., Moldeus, P., and Orrenius, S.,(1985). The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+, Journal of Biologocal Chemistry,260:13035-13040.
  • Jollow, DJ., Mitchell, JR., Potter, WZ., Davis, DC., Gillette, JR., and Brodie, BB.,(1973). Acetaminophen induced hepatic necrosis. II. Role of covalent binding in vivo, Journal of Pharmacology and Experimental Therapeutics,187:195-202.
  • Tiwari, BK., and Khosa, RL.,(2010). Hepatoprotective and antioxidant effect of Sphaeranthus indicus against acetaminophen–induced hepatotoxicity in rats,The Internet Journal of Tropical Medicine,6,1540-2681.
  • Tirmenstein, MA., and Nelson, SD.,(1990). Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides. Journal of Biological Chemistry, Feb 25,265(6),3059-3065. PMID: 2303440.
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  • Zimmerman, HJ., Maddrey, WC.,(1995). Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure,Hepatology,Sep,22(3),767-773. Erratum in: Hepatology 1995 Dec;22(6):1898. PMID: 7657281.
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  • Hossain, MA., Al-Toubi, WAS., Weli, AM., Al-Riyami, QA., and Al-Sabahi, JN.,(2013).Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem, Journal of. Taibah University Sciences,7(4),181-188.
  • Chattopadhyay, RR.,(2003). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II, Journal of Ethnopharmacology,Dec;89(2-3),217-219. doi: 10.1016/j.jep.2003.08.006. PMID: 14611885.
  • Chattopadhyay, RR., and Bandopadhyay, M., (2005). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract against paracetamol induced hepatic damage in rats: Part III, Indian Journal of Pharmacology, 37(3),184-185
  • Sithisarn, P., Supabphol, R., and Gritsanapan, W.,(2005). Antioxidant activity of Siamese neem tree (VP1209). Journal of Ethnopharmacology,99,109‑112.
  • Manikandan, P., Anandan, R., and Nagini, S.,(2009). Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and protective effects against H2O2-induced oxidative damage to pBR322 DNA and red blood cells. Journal of Agriculture and Food Chemistry, 57(15),6990-6996.
  • Al-Hashemi, ZSS., and Hossain, MA.,(2016). Biological activities of different neem leaf crude extracts used locally in Ayurvedic medicine. Pacific Science Review A: Natural Science and Engineering,18,128-131 http://dx.doi.org/10.1016/j.psra.2016.09.013
  • Priyadarsini, RV., Manikandan, P., Kumar, GH., and Nagini, S.,(2009). The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radical Research,43,492.
  • Schumacher, M., Cerella, C., Reuter, S., Dicato, M., and Diederich, M.,(2011). Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway, Genes and Nutrition,6,149.
  • Hwang, SJ., Kim, YW., Park, Y., Lee, HJ., Kim, KW., (2014). Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflammation Research,63,81.
Toplam 115 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Research Articles
Yazarlar

Pranob Jyoti Bharali Bu kişi benim 0000-0003-3677-5409

Sushanta Kumar Bordoloi Bu kişi benim 0000-0002-9249-6490

Swarnamoni Das 0000-0001-5607-1244

Kingshuk Lahon 0000-0001-9732-8472

Yayımlanma Tarihi 2 Ocak 2023
Yayımlandığı Sayı Yıl 2022 Cilt: 5 Sayı: 2

Kaynak Göster

APA Bharali, P. J., Bordoloi, S. K., Das, S., Lahon, K. (2023). Effect of chronic administration of aqueous extract of Neem (Azadirachta indica) leaves on Paracetamol-induced hepatotoxicity in Wistar albino rats. Current Perspectives on Medicinal and Aromatic Plants, 5(2), 146-161. https://doi.org/10.38093/cupmap.1167888

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