Coconut Water and Milk Modulate Intravascular Haemolysis and Hepatotoxicity Via Oxido-Inflammatory Mechanism in Rats


  • Kazeem O. Ajeigbe Department of Physiology Faculty of Basic Medical Sciences Federal University, Oye-Ekiti, Nigeria
  • Gbenga S. Adeleye Department of Physiology Faculty of Basic Medical Sciences Ekiti State University, Ado-Ekiti, Nigeria
  • Mathew W. Owonikoko Department of Physiology Faculty of Basic Medical Sciences Igbinedion University, Okada, Nigeria
  • Mayokun A. Adelakun Department of Physiology Faculty of Basic Medical Sciences Federal University, Oye-Ekiti, Nigeria
  • Olalekan E. Odesanmi Department of Biochemistry Ekiti State University, Ado-Ekiti
  • Olayinka A. Awoyinka Department of Medical Biochemistry Ekiti State University, Ado-Ekiti


antioxidants, inflammation, hepatotoxicity, haematotoxicity, coconut


Haemolysis and its associated organ pathologies are predicated upon oxidative stress and inflammation, otherwise shown to be mitigated by complement natural products. The antioxidative and anti-inflammatory effects of coconut water (CCW) and milk (CCM) in phenylhydrazine (PHZ)-induced haemolysis and hepatotoxicity in the rat was evaluated, with possible adjunctive effects with dexamethasone (DXM). Anaemic rats were treated with CCW (2 mL/100 g), CCM (2 mL/100 g), DXM (0.01 mg/Kg), CCW+DXM, and CCM+DXM for 14 days post induction. Blood samples were collected for hematological parameters, lipid profiles and liver function tests while oxidative stress markers and inflammatory cytokines were assessed in liver homogenates. PHZ caused significant reduction in concentration of all the haematological parameters, with elevated serum aminotransferases. However, CCW and CCM alone, or in combination with DXM significantly attenuated the PHZ-induced haematotoxocity and hepatoxicity. PHZ’s increase LDL and TG with decrease HDL were equally significantly reversed by CCW and CCM. Elevated tissue Malondialdehyde (MDA), Myeloperoxidase (MPO), Tumor Necrosis Factor (TNF-α), Interleukin 1beta (IL-1β) and Nuclear factor-kappa B (NF-kB) in response to PHZ were all mitigated by CCM and CCW, in favour of glutathione peroxidase (GPX), total superoxide dismutase (T-SOD) activities, total antioxidant capacity (T-AOC), Interleukin 10 (IL-10) and Nuclear factor erythroid 2-related factor 2 (NrF2). Histopathology revealed that only combination of CCM or CCW with DXM could distinctively reverse PHZ-induced alterations like macrovesicular steatosis and periportal inflammation. Phenylhydrazine induced toxicity is mitigated by either coconut water and milk or in combination with dexamethasone via oxidative stress reduction and inflammation suppression.


Cary R, Dobson S, Brooke I. Phenylhydrazine. Concise International Chemical Assessment Document, Geneva. World Health Organization. 2000

Okafor AI and Atsu CU. Ficus glumosa Del. Reduces phenylhydrazine-induced hemolytic anaemia and hepatic damage in wistar rats. JCIM. 2022; 19(3):661-668.

Wang HQ, Kong EL, Zhang X, Meng XY, Zhang JM, Yu WF, Wu FX. Folic acid alleviates jaundice of phenylhydrazine (PHA)-induced neonatal rats by reducing Lys-homocysteinylation of albumin. Cell Biol Toxicol. 2021

Coulibaly WH, Camara F, Tohoyessou MG, Konan PAK, Coulibaly K, Yapo E. G, Wiafe MA. Nutritional profile and functional properties of coconut water marketed in the streets of Abidjan (Côte d’Ivoire). Scientific African. 2023 e01616.

Probir KG, Paramita B, Souvik M, Mousumi P. Physiochemical and phytochemical analyses of copra and oil of Cocos nucifera L. (West Coast TallVariety), Int. J. Food Sci.2014;

Famurewa AC, Aja PM, Nwankwo OE, Awoke JN, Maduagwuna EK, Aloke C. Moringa oleifera seed oil or virgin coconut oil supplementation abrogates cerebral neurotoxicity induced by antineoplastic agent methotrexate by suppression of oxidative stress and neuro-inflammation in rats. J.Food Biochem. 2019; 43(3):e12748.

Famurewa AC, Maduagwuna EK, Folawiyo AM, Besong EE, Eteudo AN, Famurewa OA, Ejezie FE. Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF-ĸB/caspase-3 signaling pathway in Wistar rats. J Food Biochem. 2020; 44(1):e13100.

Geetha V and Kumar GS. Concentrates from tender coconut water and coconut testa beneficially modulates tissue lipid profiles in high-fat fed rats. J Food Sci Tech. 2022; 59(4):1649-1657.

Elsharkawy RE, Ghonem MM, Ghada N El-Sarnagawy GN, Nagy AA, Heshmat MM. Cardioprotective role of the coenzyme Q10 and coconut oil in acute aluminum phosphide poisoning: a randomized controlled clinical trial.Toxicol Res (Camb). 2023; 12(3):507-519.

Ajeigbe KO, Ndaman ZA, Amegor OF, Onifade AA, Asuk AA, Ibironke GF, Olaleye SB. Anti-Nociceptive and AntiInflammatory Potential of Coconut Water (Cocos nucifera L.) In Rats and Mice. Aust J Basic and Applied Sci. 2011; 5:1116–1122.

Ajeigbe KO, Owonikoko WM, Egbe V, Iquere I, Adeleye G. Gastroprotective and mucosa homeostatic activities of coconut milk and water on experimentally induced gastropathies in male wistar rats. Tissue and Cell. 2017; 49:528–536.

Adebayo MA, Enitan SS, Owonikoko WM, Igogo, E and Ajeigbe KO. Haematinic properties of methanolic stem bark and fruit extracts of Ficus sur in rats pre-exposed to Phenylhydrazine-induced haemolytic anaemia. Afr Journal of Biomed Res. 2017; 20(1): 85-92

Swanson JO, Pierpont G., Adicoff A. Serum high density lipoprotein cholesterol correlates with presence but not severity of coronary artery disease. Am J Med. 1981; 71(2): 235-239.

Wieland H and Seidel D. A Simple Specific Method for Precipitation of Low Density Lipoprotein. Journal of Lipid Res. 1983; 24:904-909.

Palipoch S and Punsawad C. Biochemical and histological study of rat liver and kidney injury induced by Cisplatin. J Toxicol Pathol. 2013; 26(3):293-9

Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-760

Yong, JWH, Ge L, Ng YF, and Tan SN. The chemical composition and biological properties of coconut (Cocos nucifera L.) water. Molecules. 2009;14: 5144–5164.

Pinto IFD, Silva RP, Filho A, Dantas LS, Bispo VS, Matos IA, Otsuka FAM, Santos AC, Matos HR. Study of Antiglycation, Hypoglycemic, and Nephroprotective Activities of the Green Dwarf Variety Coconut Water (Cocos nucifera L.) in Alloxan-Induced Diabetic Rats. J Med Food. 2015; 19: 802–809.

Petz LD, Garratty G. Immune Hemolytic Anemias. 2nd. Philadelphia, Pa, USA: Churchill Livingstone. 2004.

Pandey K, Meena A, Jain A, Singh, R. Molecular Mechanism of Phenylhydrazine Induced Haematotoxicity: A Review AJPCT. 2018; 2(3):390-394.

Renard D, Rosselet A. Drug induced hemolytic anaemia: Pharmacological aspects. Transfus Clin Biol. 2017; (3):110-114

Kale OE, Awodele O, Akindele AJ. Protective Effects of Acridocarpus smeathmannii (DC) Gill. & Perr. Root Extract against Phenylhydrazine-induced Haematotoxicity, Biochemical changes, and Oxidative stress in Rats. Biochemistry Insights. 2019; 12: 1-14.

Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med. 2012; 18(9):1407-12.

Zhang H, Niu Y, Gu H, Lu S, Su W, Lin N, Li X, Yang Z, Qin L, Su Q. The association between white blood cell subtypes and prevalence and incidence of nonalcoholic fatty liver disease. Eur J Inflamm. 2019.

Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, Tsujita T, Dillon JF, Ashford ML, Hayes JD (2010). Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Rad Biol Med. 2010; 48(2): 357-371.

Lambert MP. Platelets in liver and renal disease. Hematology: The American Society of Hematology Education Program. 2016(1), 251-255.

Yang T, Wang L, Yan T, Zhang T, Zhou W, Chen F, Chen Y, Zheng J, Duan P, Li, F. Platelet count is closely associated with the severity of liver injury in patients with chronic hepatitis B virus infection: A cross-sectional study. Exp Ther Med 2020; 20(1): 243-250.

Privitera G, Spadaro L, Marchisello S, Fede G, Purrello F. Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance. Dig Dis Sci. 2018 63(1):16-26

Paul B, Lewinska M, Andersen JB. Lipid alterations in chronic liver disease and liver cancer. JHEP Reports: Innovation in Hepatology. 2022; 4(6):100479

Luo L, Pu X, Wang Y, Xu N. Impaired plasma lipid profiles in acute hepatitis. Lip Health and Dis. 2010; 9:5.

Cheng R, Tan N, Kang Q, Luo H, Chen H, Pan J, Han Y, Yang Y, Xu X. High-density lipoprotein cholesterol is a predictor of survival in cirrhotic patients with acute gastrointestinal bleeding: a retrospective study. BMC Gastroenterol. 2020; 20: 381

McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. (2012). The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest. 2012; 122:1574–1583.

Ndubuka GI, Okafor WC, Jervas E, Chidi IS, Udoka C, Ikechukwu O. Protective Effect of Immature Coconut Water on Hepatocytes against Carbon tetrachloride-induced Liver Damage in Wister Rats. Int J Sci Res. 2015; 4(12).

Bispo VS, Dantas LS, Chaves AB Filho, Pinto IFD, Silva RPD, Otsuka FAM, Santos RB, Santos AC, Trindade DJ, Matos HR. Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol. An Acad Bras Cienc. 2017; 89(2):1095-1109.

Nematollahi HR, Hosseini R, Bijani A, Akhavan-Niaki H, Parsian H, Pouramir M, Saravi M, Bagherzadeh M, Mosapour A, Saleh-Moghaddam M, Rajabian M, Golpour M, Mostafazadeh A. Interleukin 10, lipid profile, vitamin D, selenium, metabolic syndrome, and serum antioxidant capacity in elderly people with and without cardiovascular disease: Amirkola health and ageing project cohort-based study. ARYA Atherosclerosis, 2019; 15(5), 233-240.

Banerjee A, Dey T, Majumder R, Bhattacharya T, Dey S, Bandyopadhyay D, Chattopadhyay A. Oleic acid prevents erythrocyte death by preserving haemoglobin and erythrocyte membrane proteins. Free Radic Biol Med. 2023; 202:17-33.

Bhagya D, Prema L, Rajamohan T. Therapeutic effects of tender coconut water on oxidative stress in fructose fed insulin resistant hypertensive rats. Asian Pac J Trop Med. 2012: 5(4), 270–276.

Rao SS, and Najam R. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation. J Intercult Ethnopharmacol. 2016: 5(3): 244–249.

Shwetha BR, Siddalingaprasad HS, Shivukumar S, Nagalakshmi NC, Hariprasad MG. Mechanism of haematotoxicity induced by phenylhydrazine: a review. Journal of Applied Pharmaceutical Research. 2019; 7(4):1 – 6 .

Manna K, Khan A, Das D, BandhuKesh S, Das U, Ghosh S, SharmaDey R, Das Saha K, Chakraborty A, Chattopadhyay S, Dey S, Chattopadhyay D. (2014). Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NF-κB and activation of Nrf2 pathway. J Ethnopharmacol. 2014; 155(1), 132-146.

Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-kappa B activation by small molecules as a therapeutic strategy. Biochem. Biophys. Acta 2010; 1799:775–787.

Ahn KS, Aggarwal BB. Transcription factor NF-kappa B: a sensor for smoke and stress signals. Ann. NY Acad. 2005; Sci. 1056, 218–233.

Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 2007; 117, 1175–1183.

Shih RH, Wang CY, Yang CM. NF-kappa B Signaling Pathways in Neurological Inflammation: A Mini Review. Front. Mol. Neurosci. 2015; 8:77.

Jayasooriya RG, Lee KT, Lee HJ, Choi YH, Jeong JW, Kim GY. Anti-inflammatory effects of β-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway. Food Chem Toxicol 2014; 65:82-9

Lakshmanan J, Zhang B, Wright K, Motameni AT, Jaganathan V, Schultz DJ, Klinge CM, Harbrecht BG. Tender coconut water suppresses hepatic inflammation by activating AKT and JNK signaling pathways in an in vitro model of sepsis. J Funct Foods.2020;64.



How to Cite

Ajeigbe, K. O., Adeleye, G. S., Owonikoko, M. W., Adelakun, M. A., Odesanmi, O. E., & Awoyinka, O. A. (2023). Coconut Water and Milk Modulate Intravascular Haemolysis and Hepatotoxicity Via Oxido-Inflammatory Mechanism in Rats: Tropical Journal of Natural Product Research (TJNPR), 7(11), 5308–5315. Retrieved from