Ameliorative Effect of Nutmeg (Myristica fragrans) Supplement against Acetaminophen - Induced Hepato-Renal Toxicity in Wistar Rats

Main Article Content

Chukwunyere Ogechi Abaekwume
Hope Delesi Kagbo

Abstract

Background: Recently, many drugs have been developed and used for the treatment of hepatic and renal diseases. Nutmeg apart from being utilized as kitchen spices in Nigeria has also been used for healing and medicinal purposes.

Aims: In the present study, nutmeg supplement was evaluated against Acetaminophen (APAP) induced hepato- renal-toxicity.

Study Design: Twenty (20) adult wistar rats weighing185-220 were obtained from animal house of the department of  Pharmacology University of Port Harcourt were divided into four groups having 5 rats each (n=5).

Methodology: The animals were divided into four groups of 5 rats each: Group A (normal control) were administered distilled water, group B (negative control) received a single dose of acetaminophen (1000 mg/kg) for two days. Group C received 500 mg/kg body weight of nutmeg supplement one hour before receiving 1000 mg/kg acetaminophen, while group D received acetaminophen (1000 mg/kg) only on day 1 and 2 and the drug extracts on day 3-7. All dosage was dissolved in distilled water orally. The experiment lasted for seven days. Twenty four hours after drugs administrations the animals in each group were anaesthetized. Blood samples were collected and animals sacrificed, liver and kidney tissues removed for various histopathological, biochemistry, antioxidant and haematological examinations using standard procedures. Statistical analysis was done using ANOVA and Tukey poc-hoc Test.

Results: Administration of nutmeg supplement orally effectively restrained APAP-induced alterations in the activities of hepatic (48.60-38.00) and renal markers and Antioxidant enzymes in liver (0.43-0.53). The hepatic and renal architecture of APAP administered rats showed distorted liver and kidney tissues, hepatic vacuolations, destroyed glomerular and renal tubules. Nutmeg+APAP as well as APAP+ Nutmeg administrations were able to ameliorate the effects of APAP administration.

Conclusion: The result indicated that APAP overdosed is hepato-renal- toxic and Nutmeg supplement possessed hepato-prote-curative properties as well as renal-prote-curative properties against APAP-induced damage in rats.

Keywords:
Acetaminophen, antioxidant enzymes, biochemistry and hepato-renal-protective agents.

Article Details

How to Cite
Abaekwume, C. O., & Kagbo, H. D. (2020). Ameliorative Effect of Nutmeg (Myristica fragrans) Supplement against Acetaminophen - Induced Hepato-Renal Toxicity in Wistar Rats. Journal of Advances in Medical and Pharmaceutical Sciences, 22(11), 1-14. https://doi.org/10.9734/jamps/2020/v22i1130200
Section
Original Research Article

References

Shana K. The mammalian kidney: How nephrons perform osmoregulation. Biology Gatech. Ed.; 2016.

Ozougwu JC. Physiology of the liver. International Journal of Research in Pharmaceutical Sciences and Biosciences. 2017;4(8):13-24.

Venkatesan SP, Deecaraman M, Vijayalakshmi M, Sakthivelan SM. Sub-acute toxicity studies of acetaminophen in Sprague rats. Biology and Pharmaceutical Bulletin. 2014;37(7):1184-1190.

Lee WW. Acetaminophen (APAP) hepatotoxicity isn’t it time to go away? Journal of Hepatology; 2017. (Pubmed PMID 28734939).

Mahmoud MF, Diaai AA, Ahmed F. Evaluation of the efficacy of ginger, Arabic gum and Boswellia in acute and chronic renal failure. Renal Failure. 2012;34:73-82. DOI:http://doi.org/10.3109/0886022x.2011.623563

Michael MC. Essential biology for senior secondary schools. Eds. Lagos Nigeria; Tonad Publishers Ltd. 2018;262-265,294-300.

Mazhar F, Akram S. Acute renal damage in acetaminophen poisoining. Journal of Young Pharmacology. 2016;8(4):505-506.

Ozougwu JC, Eyo J. Hepatoprotective effects of Allum cepa (onions) against paracetamol induced liver damage in rats. African Journal of Biotechnology. 2014;13(26):2679-2688.

Dkhil M, Abdel-Moneim AE, Hafiz T, Mubaraki M, Walid F, Al-Quraishy S, et al. Myristica fragrans kernels prevent paracetamol-induced hepatotoxicity by inducing ant-apoptotic genes and Nrf2/ Ho-I pathway. International Journal of Moleculari Sciences. 2019;20(4):993.

Dulger G. Herbal drugs and drug interactions. Marmara Pharmaceutical Journal. 2012;16:9-22.

Hauwa SB, Baba G, Yusuf H. Haematological and histological changes induced on the selected organs of (wistar) rats by leaf extracts from herbs of ethno medical applications. Nigerian Journal of Chemical Research. 2013;18:48-57.

Moncel B. What is nutmeg? www.the spruceeats.com; 2017.

Aboelhassan DM, Hafiz NA, Darwish HR, Shabana ME, Eshak MG, Hassanane MM, et al. Enhancing effects of Moringa oleifera leaf extract on carcinogenic Aflatoxin B1- induced genetic alterations, haematoxicity and histological changes in liver and kidney of rats. J ISISN. 2013;15(2):814-833.

Wang X, Wu Q, Liu A, Anadon A, Rodriguez JC, Martinez-Larranaga ML, et al. Paracetamol: Overdosed induced oxidative stress toxicity, metabolism and protective effect of various compounds in vivo and in vitro. Drug Metabolism Reviews; 2017. (Pubmed PMID 28766385).

Hartanto S, Ko HS, Jee HS, Kang UJ, Seb ST, Ohh SJ. Effect of dietary nutmeg on heat stress tolerance- related parameters in Korean. J. Anim Physiol a Nutr. 103(4). DOI: 10.1111/JPn.13113

Karthivashan G, Kura AU, Arulselvan P, Norhaszalina MI, Fakurazi S. The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant system and inflammatory markers in an acetaminophen-induced nephrotoxic mice model. Peer Journal Do. 2016;10:7717, peerj. 2127.

Mathew C, Nair C, Shenoy T, Varghese J. Preventive and curative effects of Acalypha indica on acetaminophen induced hepatotoxicity. International Journal of Green Pharmacy. 2011;49-54.

Abdel-Azim SA, Abdel-Rahem MT, Said MM, Khattab A. Protective effect of Moringa peregrine leaves extract on acetaminophen-induced liver toxicity in albino rats. AJICAM. 2017;14(2):206-216.

Toussaint K, Yang XC, Zielinski MA, Reigle KI, Sacavage SD. What do we (not) know about how paracetamol (acetaminophen) works? Journal of Clinical Pharmacy and Therapeutics. 2011;35:617-638.

Singh SM, Kushwah SR, Kumar. Acetaminophen (Paracetamol) drug overdosed, toxic effect on human health. International Journal of Recent Scientific Research; 2017

El Badwi SM, Al Tayib OA. Assessment of ameliorative effects of aqueous extracts of Moringa oleifera on acetaminophen- induced nephrotoxicity in rats. JOSR (LOSR-JHSS). 2016;21(9):1-7.

Abdel-Azeem AS, Hegazu AM, Abraham K, Mahmuod A, El-Sayed H. Hepatoprotective, antioxidant and ameliorative effects of ginger (Zinger officinale Roscoe) and vitamin E in acetaminophen treated rats. J. Die Suppl. 2013;10(3):195-209.

Hamilton S, Terentyer D. Altered intracellular calcium homeostasis and arrhythmogenesis in the aged heart. International Journal of Molecular Sciences. 2019;20(2386):1-22.

Reddy TS, Shama KP, Nirmala P, Shastry CS. Biochemical studies on hepato and nephroprotective effect of Butterfly Tree (Bauhinia purpures Linn) against acetaminophen – induced toxicity. International Journal of Research in Ayurveda and Pharmacy. 2012;3(3):455-460.

Reddy UT, Lakshmi M, Kumar S, Kumar D. Protective effect of Abutilon indicum L. (Malvaceae) against acetaminophen induced nephrotoxicity in rats. Journal of Life Science. 2013;1:40-43.

Swaroopa M. Effect of ginger extract consumption on renal function during ethanol withdrawal induced-stress. IJIR, Engineering and Technology. 2013;6412-6418.

Mammucari CA, Raffelo A, Reane DV, Gherardi G, Rhizzuto AR. Mitochondrial calcium. European Journal of Physiology. 2018;470(8):1165-1179.

Al-Qudah MMA, Haddad MA, EL-Qudah JMF. The effects of aqueous ginger extract on pancreas histology and on blood glucose in normal and alloxan monohydrate-induced diabetic rats. Bio Res. 2016;27:350-356. Available:https://www.researchgate.net/publication/301649907_The_effects_of_aqueous

Al-Qudah MMA, Al-Ramanneth ED, Haddad MA, Al-Abbadi A. The effects of aqueous ginger extract on kidney and lungs of diabetic rats. IJB. 2018;10(4):23-28.

Subramaya S, Venkataraman B, Meeran MFN, Goyal SN, Patil CR, Shreesh O. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen induced liver injury. International Journal of Molecular Sciences. 2019;19:3776-3918.

Masoud RE. Hepatoprotective effect of curcuimin versus silymarin on paracetamol induced hepatotoxicity in rats. Intern Jour of Pharmacol and Biol Sciences. 2017;8(2):134-141.

Mohammad SI, Mustafa IA, Abdulqader SZ. Ameliorative effects of aqueous extract of Zingiber officinale on the cadmiun-induced liver and kidney injury in female rats. Jordan Journal of Biological Sciences. 2013;6(3):231-234.

Pathan MM, Khan MA, Moregaonkar SD, Somkuwar AP, Gaikwad NZ. Amelioration of paracetamol-induced nephrotoxicity by Maytenus emarginata in male wistar rats. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(4):471-474.

Paliwal R, Sharma V, Precheta S, Yadav S, Sharma S. Anti-nephrotoxic effect of administration of Moringa oleifera Lam in amelioration of DMBA induced renal carcinogenesis in swiss albino mice. Biology and Medicine. 2011;3(2):27-35.

Sharifudin S, Fakurazi M, Hidayat M, Hairuszah M, Moklas P, Arulselvan. Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats. Pharmaceutical Biology. 2013;51:279-88.

Hassanem NHM. Protective effect of nutmeg and Rosemary on oxidative stress in hypercholesterolamic rats. International Journal of Nutrition and Food Sciences. 2015;4(4):465-476.

Salehi B, Martorelli M, Albiser JC, Sureda A, Martins, Maurya PKM, Sharifirad M, et al. Antioxidant: Positive or negative actors? Biomolecules. 2018;8:124.

Ali MD, Naseer MA, Mirza MA, Alam MS. Haematological, biochemical and histopathological study of the plant extract of Terminalia chebula Rentz, Aloe vera Linn and Tamarindus indica Linn on animal model. A comparative study. National Journal of Physi, Pharm and Pharmacol. 2019;9(3):268-274.

Oyedeji KO, Bolrinwa AF, Ojeniran SS. Effects of Paracetamol (APAP) on haematological and reproductive parameters in male albino rats. International Journal of Pharmaceutical Sciences Review and Research. 2013;20(2):296-300.

Bachri MS, Yullaris S, Sari AK. Effects of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to haematological parameters in rats. IOP Publishing Ltd. 2017;289.

Slaoui M, Fiette L. Histopathology procedures: From tissue sampling to histophatological evaluation. Methods in Molecular Biology (Clifton N J). 2011;691:69-82.

Eweka AO, Eweka A. Histological effects of oral administrations of nutmeg on the kidneys of adult wistar rats. North American Journal of Medical Sciences. 2010;2(4): 189-192.

Mustapha RO. The easier approach to pharmacology for all health professionals. Akins Media Prints 3rd eds., Kwara; 2012.

Farrell SE and Miller MA. How are renal function test used in the work up of acetaminophen toxicity/poisoning; 2020. Available:www.medscage.com

Yoon E, Babar A, Choudhary M, Kutnev M, Pyrsopoulos N. Acetaminophen induced hepatotoxicity. A comprehensive update. J, Clen, Transl Heptatol. 2016; 4:131-142.

Ugwuona FU, Onweluzo JC, Ojimelukwe PC. African nutmeg (Monodora myristica) Posseses Antioxidant Properties and can preserve African bread-fruit (Treculia Africana) seed and flour. ACTA Sci Nutr Health. 2019;3(6):41-50.

Yadav A, Kumari R, Yadav A, Mishra JP. Antioxidants and its functions in human body. A review; 2016. Available:www.researchgate.net

Kadiri HE and Okoro IO. The Antioxidant effect of aqueous extract of Monodora myristica on cyanide induced Hepatic and Renal Toxicity in Rats. Nig. J. Pure an Appl Sci. 2018;31(2):8.

Ahmed S, Abdelhaud F, Abdalla O. Effects of rosemary oil against hemato-biochemical alterations and renal oxidative damage induced by paracetamol in rats. Annals of Veterinary and Animal Science (AVAS). 2019;6(5).Shana K. The mammalian kidney: How nephrons perform osmoregulation. Biology Gatech. Ed.; 2016.

Ozougwu JC. Physiology of the liver. International Journal of Research in Pharmaceutical Sciences and Biosciences. 2017;4(8):13-24.

Venkatesan SP, Deecaraman M, Vijayalakshmi M, Sakthivelan SM. Sub-acute toxicity studies of acetaminophen in Sprague rats. Biology and Pharmaceutical Bulletin. 2014;37(7):1184-1190.

Lee WW. Acetaminophen (APAP) hepatotoxicity isn’t it time to go away? Journal of Hepatology; 2017. (Pubmed PMID 28734939).

Mahmoud MF, Diaai AA, Ahmed F. Evaluation of the efficacy of ginger, Arabic gum and Boswellia in acute and chronic renal failure. Renal Failure. 2012;34:73-82. DOI:http://doi.org/10.3109/0886022x.2011.623563

Michael MC. Essential biology for senior secondary schools. Eds. Lagos Nigeria; Tonad Publishers Ltd. 2018;262-265,294-300.

Mazhar F, Akram S. Acute renal damage in acetaminophen poisoining. Journal of Young Pharmacology. 2016;8(4):505-506.

Ozougwu JC, Eyo J. Hepatoprotective effects of Allum cepa (onions) against paracetamol induced liver damage in rats. African Journal of Biotechnology. 2014;13(26):2679-2688.

Dkhil M, Abdel-Moneim AE, Hafiz T, Mubaraki M, Walid F, Al-Quraishy S, et al. Myristica fragrans kernels prevent paracetamol-induced hepatotoxicity by inducing ant-apoptotic genes and Nrf2/ Ho-I pathway. International Journal of Moleculari Sciences. 2019;20(4):993.

Dulger G. Herbal drugs and drug interactions. Marmara Pharmaceutical Journal. 2012;16:9-22.

Hauwa SB, Baba G, Yusuf H. Haematological and histological changes induced on the selected organs of (wistar) rats by leaf extracts from herbs of ethno medical applications. Nigerian Journal of Chemical Research. 2013;18:48-57.

Moncel B. What is nutmeg? www.the spruceeats.com; 2017.

Aboelhassan DM, Hafiz NA, Darwish HR, Shabana ME, Eshak MG, Hassanane MM, et al. Enhancing effects of Moringa oleifera leaf extract on carcinogenic Aflatoxin B1- induced genetic alterations, haematoxicity and histological changes in liver and kidney of rats. J ISISN. 2013;15(2):814-833.

Wang X, Wu Q, Liu A, Anadon A, Rodriguez JC, Martinez-Larranaga ML, et al. Paracetamol: Overdosed induced oxidative stress toxicity, metabolism and protective effect of various compounds in vivo and in vitro. Drug Metabolism Reviews; 2017. (Pubmed PMID 28766385).

Hartanto S, Ko HS, Jee HS, Kang UJ, Seb ST, Ohh SJ. Effect of dietary nutmeg on heat stress tolerance- related parameters in Korean. J. Anim Physiol a Nutr. 103(4). DOI: 10.1111/JPn.13113

Karthivashan G, Kura AU, Arulselvan P, Norhaszalina MI, Fakurazi S. The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant system and inflammatory markers in an acetaminophen-induced nephrotoxic mice model. Peer Journal Do. 2016;10:7717, peerj. 2127.

Mathew C, Nair C, Shenoy T, Varghese J. Preventive and curative effects of Acalypha indica on acetaminophen induced hepatotoxicity. International Journal of Green Pharmacy. 2011;49-54.

Abdel-Azim SA, Abdel-Rahem MT, Said MM, Khattab A. Protective effect of Moringa peregrine leaves extract on acetaminophen-induced liver toxicity in albino rats. AJICAM. 2017;14(2):206-216.

Toussaint K, Yang XC, Zielinski MA, Reigle KI, Sacavage SD. What do we (not) know about how paracetamol (acetaminophen) works? Journal of Clinical Pharmacy and Therapeutics. 2011;35:617-638.

Singh SM, Kushwah SR, Kumar. Acetaminophen (Paracetamol) drug overdosed, toxic effect on human health. International Journal of Recent Scientific Research; 2017

El Badwi SM, Al Tayib OA. Assessment of ameliorative effects of aqueous extracts of Moringa oleifera on acetaminophen- induced nephrotoxicity in rats. JOSR (LOSR-JHSS). 2016;21(9):1-7.

Abdel-Azeem AS, Hegazu AM, Abraham K, Mahmuod A, El-Sayed H. Hepatoprotective, antioxidant and ameliorative effects of ginger (Zinger officinale Roscoe) and vitamin E in acetaminophen treated rats. J. Die Suppl. 2013;10(3):195-209.

Hamilton S, Terentyer D. Altered intracellular calcium homeostasis and arrhythmogenesis in the aged heart. International Journal of Molecular Sciences. 2019;20(2386):1-22.

Reddy TS, Shama KP, Nirmala P, Shastry CS. Biochemical studies on hepato and nephroprotective effect of Butterfly Tree (Bauhinia purpures Linn) against acetaminophen – induced toxicity. International Journal of Research in Ayurveda and Pharmacy. 2012;3(3):455-460.

Reddy UT, Lakshmi M, Kumar S, Kumar D. Protective effect of Abutilon indicum L. (Malvaceae) against acetaminophen induced nephrotoxicity in rats. Journal of Life Science. 2013;1:40-43.

Swaroopa M. Effect of ginger extract consumption on renal function during ethanol withdrawal induced-stress. IJIR, Engineering and Technology. 2013;6412-6418.

Mammucari CA, Raffelo A, Reane DV, Gherardi G, Rhizzuto AR. Mitochondrial calcium. European Journal of Physiology. 2018;470(8):1165-1179.

Al-Qudah MMA, Haddad MA, EL-Qudah JMF. The effects of aqueous ginger extract on pancreas histology and on blood glucose in normal and alloxan monohydrate-induced diabetic rats. Bio Res. 2016;27:350-356. Available:https://www.researchgate.net/publication/301649907_The_effects_of_aqueous

Al-Qudah MMA, Al-Ramanneth ED, Haddad MA, Al-Abbadi A. The effects of aqueous ginger extract on kidney and lungs of diabetic rats. IJB. 2018;10(4):23-28.

Subramaya S, Venkataraman B, Meeran MFN, Goyal SN, Patil CR, Shreesh O. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen induced liver injury. International Journal of Molecular Sciences. 2019;19:3776-3918.

Masoud RE. Hepatoprotective effect of curcuimin versus silymarin on paracetamol induced hepatotoxicity in rats. Intern Jour of Pharmacol and Biol Sciences. 2017;8(2):134-141.

Mohammad SI, Mustafa IA, Abdulqader SZ. Ameliorative effects of aqueous extract of Zingiber officinale on the cadmiun-induced liver and kidney injury in female rats. Jordan Journal of Biological Sciences. 2013;6(3):231-234.

Pathan MM, Khan MA, Moregaonkar SD, Somkuwar AP, Gaikwad NZ. Amelioration of paracetamol-induced nephrotoxicity by Maytenus emarginata in male wistar rats. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(4):471-474.

Paliwal R, Sharma V, Precheta S, Yadav S, Sharma S. Anti-nephrotoxic effect of administration of Moringa oleifera Lam in amelioration of DMBA induced renal carcinogenesis in swiss albino mice. Biology and Medicine. 2011;3(2):27-35.

Sharifudin S, Fakurazi M, Hidayat M, Hairuszah M, Moklas P, Arulselvan. Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats. Pharmaceutical Biology. 2013;51:279-88.

Hassanem NHM. Protective effect of nutmeg and Rosemary on oxidative stress in hypercholesterolamic rats. International Journal of Nutrition and Food Sciences. 2015;4(4):465-476.

Salehi B, Martorelli M, Albiser JC, Sureda A, Martins, Maurya PKM, Sharifirad M, et al. Antioxidant: Positive or negative actors? Biomolecules. 2018;8:124.

Ali MD, Naseer MA, Mirza MA, Alam MS. Haematological, biochemical and histopathological study of the plant extract of Terminalia chebula Rentz, Aloe vera Linn and Tamarindus indica Linn on animal model. A comparative study. National Journal of Physi, Pharm and Pharmacol. 2019;9(3):268-274.

Oyedeji KO, Bolrinwa AF, Ojeniran SS. Effects of Paracetamol (APAP) on haematological and reproductive parameters in male albino rats. International Journal of Pharmaceutical Sciences Review and Research. 2013;20(2):296-300.

Bachri MS, Yullaris S, Sari AK. Effects of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to haematological parameters in rats. IOP Publishing Ltd. 2017;289.

Slaoui M, Fiette L. Histopathology procedures: From tissue sampling to histophatological evaluation. Methods in Molecular Biology (Clifton N J). 2011;691:69-82.

Eweka AO, Eweka A. Histological effects of oral administrations of nutmeg on the kidneys of adult wistar rats. North American Journal of Medical Sciences. 2010;2(4): 189-192.

Mustapha RO. The easier approach to pharmacology for all health professionals. Akins Media Prints 3rd eds., Kwara; 2012.

Farrell SE and Miller MA. How are renal function test used in the work up of acetaminophen toxicity/poisoning; 2020. Available:www.medscage.com

Yoon E, Babar A, Choudhary M, Kutnev M, Pyrsopoulos N. Acetaminophen induced hepatotoxicity. A comprehensive update. J, Clen, Transl Heptatol. 2016; 4:131-142.

Ugwuona FU, Onweluzo JC, Ojimelukwe PC. African nutmeg (Monodora myristica) Posseses Antioxidant Properties and can preserve African bread-fruit (Treculia Africana) seed and flour. ACTA Sci Nutr Health. 2019;3(6):41-50.

Yadav A, Kumari R, Yadav A, Mishra JP. Antioxidants and its functions in human body. A review; 2016. Available:www.researchgate.net

Kadiri HE and Okoro IO. The Antioxidant effect of aqueous extract of Monodora myristica on cyanide induced Hepatic and Renal Toxicity in Rats. Nig. J. Pure an Appl Sci. 2018;31(2):8.

Ahmed S, Abdelhaud F, Abdalla O. Effects of rosemary oil against hemato-biochemical alterations and renal oxidative damage induced by paracetamol in rats. Annals of Veterinary and Animal Science (AVAS). 2019;6(5).