Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.
References
[1]
Sharief, D. (2014) Effect of Moringa oleifera against Stannous Chloride Toxicity in Rats Rattus norvegicus. International Journal of Pharmaceutical & Biological Archive, 4, 771-774.
[2]
Verma, S. and Singh, S. (2008) Current and Future Status of Herbal Medicines. Veterinary World, 1, 347-350. https://doi.org/10.5455/vetworld.2008.347-350
[3]
Mbikay, M. (2012) Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review. Frontiers in Pharmacology, 3, 24.
https://doi.org/10.3389/fphar.2012.00024
[4]
Kasolo, J.N., Bimenya, G.S., Ojok, L., Ochieng, J. and Ogwal-Okeng, J.W. (2010) Phytochemicals and Uses of Moringa oleifera Leaves in Ugandan Rural Communities. Journal of Medicinal Plants Research, 4, 753-757.
[5]
Konmy, B.B., Olounladé, P.A., Azando, E.B.V. and Hounzangbe-Adote, S.E.G. (2016) A Review on Phytochemistry and Pharmacology of Moringa oleifera Leaves (Moringaceae). Journal of Pharmacognosy and Phytochemistry, 5, 325.
[6]
Kasolo, J.N., Bimenya, G.S., Okwi, A.L., Othieno, E.M. and Ogwal-Okeng, J.W. (2012) Acute Toxicity Evaluation of Moringa oleifera Leaves Extracts of Ethanol and Water in Mice. The African Journal of Animals & Biomedical Sciences, 7, 40-44.
[7]
Kasolo, J.N., Bimenya, G.S., Ojok, L. and Ogwal-Okeng, J.W. (2012) Sub-Acute Toxicity Evaluation of Moringa oleifera Leaves Aqueous and Ethanol Extracts in Swiss Albino Rats. International Journal of Medicinal Plant Research, 1, 75-81.
[8]
Atkuri, K.R., Mantovani, J.J., Herzenberg, L.A. and Herzenberg, L.A. (2007) N-Acetylcysteine a Safe Antidote for Cysteine/Glutathione Deficiency. Current Opinion in Pharmacology, 7, 355-359. https://doi.org/10.1016/j.coph.2007.04.005
[9]
Zafarullah, M., Li, W., Sylvester, J. and Ahmad, M. (2003) Molecular Mechanisms of N-Acetylcysteine Actions. Cellular and Molecular Life Sciences CMLS, 60, 6-20.
https://doi.org/10.1007/s000180300001
[10]
Gordon, K. (2001) The OECD Guidelines and Other Corporate Responsibility Instruments.
[11]
Harborne, J. (1984) Methods of Plant Analysis. In: Phytochemical Methods, Springer, Berlin, 1-36. https://doi.org/10.1007/978-94-009-5570-7
[12]
Arfsten, D.P., Johnson, E.W., Thitoff, A.R., Jung, A.E., Wilfong, E.R., Lohrke, S.M., Bobb, A.J., et al. (2004) Impact of 30-Day Oral Dosing with N-acetyl-L-cysteine on Sprague-Dawley Rat Physiology. International Journal of Toxicology, 23, 239-247.
https://doi.org/10.1080/10915810490502041
[13]
Adedapo, A., Mogbojuri, O. and Emikpe, B. (2009) Safety Evaluations of the Aqueous Extract of the Leaves of Moringa oleifera in Rats. Journal of Medicinal Plants Research, 3, 586-591.
[14]
Ekam, V. and Ebong, P. (2007) Serum Protein and Enzyme Levels in Rats Following Administration of Antioxidant Vitamins during Caffeinated and Non-Caffeinated Paracetamol Induced Hepatotoxicity. Nigerian Journal of Physiological Sciences, 22, 65-68. https://doi.org/10.4314/njps.v22i1-2.54894
[15]
Olayemi, A.T., Olanrewaju, M.J. and Oloruntoba, A.C. (2016) Toxicological Evaluation of Moringa oleifera Lam Seeds and Leaves in Wistar Rats. Pharmacognosy Communications, 6, 100-111. https://doi.org/10.5530/pc.2016.2.8
[16]
Fakurazi, S., Sharifudin, S.A. and Arulselvan, P. (2012) Moringa oleifera Hydroethanolic Extracts Effectively Alleviate Acetaminophen-Induced Hepatotoxicity in Experimental Rats through Their Antioxidant Nature. Molecules, 17, 8334-8350.
https://doi.org/10.3390/molecules17078334
[17]
Lauterburg, B.H., Corcoran, G.B. and Mitchell, J.R. (1983) Mechanism of Action of N-acetylcysteine in the Protection against the Hepatotoxicity of Acetaminophen in Rats in Vivo. The Journal of Clinical Investigation, 71, 980-991.
https://doi.org/10.1172/JCI110853
[18]
Han, D., Shinohara, M., Ybanez, M.D., Saberi, B. and Kaplowitz, N. (2010) Signal Transduction Pathways Involved in Drug-Induced Liver Injury. In: Adverse Drug Reactions, Springer, Berlin, 267-310. https://doi.org/10.1007/978-3-642-00663-0_10