Nephroprotective Activities of Ethanol Root Extract and Fractions of Hippocratea africana Against Doxorubicin-Induced Kidney Toxicity

Kufre U. Noah, John A. Udobang, Jude E. Okokon, Martin O. Anagboso, Nwakaego Omonigho Ebong

Abstract


Hippocratea africana root used locally in the treatment of poisoning was investigated to confirm its antidotal potential in rats. The root extract (200-600 mg/kg) and fractions; dichloromethane (DCM) and aqueous, 400 mg/kg) were evaluated for nephroprotective activity against doxorubicin-induced kidney injury in rats. Kidney function parameters, kidney oxidative stress markers and kidney histology were used to assess the kidney protective effect of the extract. The root extract and fractions (200-600 mg/kg) significantly (p<0.05-0.01) reduced the levels of creatinine, urea and electrolytes that were elevated by doxorubicin. Also, the MDA level elevated by doxorubicin was reduced by the extract and fractions co-administration, while the levels of GSH, GST, SOD, GPx, and CAT that were decreased by doxorubicin were significantly (p<0.01) elevated by the root extract/fractions. Histology of the kidney sections of extract/fractions -treated animals showed reductions in the pathological features compared to the organotoxic-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked nephroprotective potential. The anti-toxic effect of this plant may in part be mediated through the chemical constituents of the plant. The plant, Hippocratea africana possesses anti-toxicant properties which can be exploited in the treatment of doxorubicin related toxicities.

Keywords


Renoprotective; Hippocratea africana; doxorubicin; oxidative stress

Full Text:

PDF

References


Abdel-Daim MM, kilany OE, Khalifa HA, Ahmed AAM. (2017). Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Cancer Chemotherapy and Pharmacology 80(4): 745–753.

Abushouk AI, Ismail A, Salem AMA, Afifi AM, Abdel-Daim MM. (2017). Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity. Biomedicine & Pharmacotherapy 90: 935–946.

Abushouk AI, Salem AMA, Saad A. (2019). Mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy: potential mechanisms, governing factors, and implications of the heart stem cell debate. Frontiers in Pharmacology 10: 635.

Ajibesin K K, Ekpo BA, Bala D N, Essien E E, Adesanya SA.2008. Ethnobotanical survey of Akwa Ibom State of Nigeria. J Ethnopharm 115: 387 – 408.

Bachur NR, Gordon SL, Gee MV, Kon H. (1979). NADPH-cytochrome P450 reductase activation of quinone anticancer agents to free radicals. Proceedings of the National Academy of Sciences USA 76: 954-957.

Burkill HM. 2000. The useful plants of West Tropical Africa. 2nd Edition. Volume 5, Families S–Z, Addenda. Royal Botanic Gardens, Kew, United Kingdom. 686 pp.

Calabresi P, Chabner BA. (1990) Chemotherapy of neoplastic diseases, In: Gilman AG, Rall TW, Nies AS, Taylor P. (eds.). The Pharmacological Basis of Therapeutics. NY: Pergamon Press Inc. pp. 1203-1263.

Drury RA, Wallington EA. (1980) Carleton’s Histological Techniques. 5th Edition, Oxford University Press, New York, 195.

Ellman GL. (1959). Tissue sulfhydryl groups. Archieves of Biochemistry and Biophysics. 82: 70-77.

Esterbauer H, Cheeseman KH. (1990). Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods in Enzymology 186: 407–421.

Gunes FE. 2013. Medical Use of squalene as a natural antioxidant. Journal of Marmara University Institute of Health Sciences 3(4):220-228.

Gupta R, Sharma AK, Dobhal MP, Sharma MC and Gupta RS. (2011). Antidiabetic and antioxidant potential of ?-sitosterol in streptozotocin-induced experimental hyperglycemia. Journal of Diabetes 3(1):29-37.

Gupta RK, Hussain T, Panigrahi G, Das A, Singh GN, Sweety K, Faiyazuddin MD and Rao CV. (2011a). Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals. Asian Pacific Journal of Tropical Medicine 6: 964-968.

Hutchinson J, Dalziel JM. 1973. Flora of West Tropical Africa. 2nd edition. Crown Agents for Overseas Government and Administration, Vol.1, Part 2, p.638

Injac R, Perse M, Cerne M, Potocnik N, Radic N, Govedarica B, Djordjevic A, Cerar A, Strukelj B. (2009). Protective effects of fullerenol C60 (OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer. Biomaterials 30: 1184-1196.

Kalender Y, Yel M, Kalender S. (2005). Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin. Toxicology 209: 39-45.

Khames A, Khalaf MM, Gad AM, Abd El-Raouf OM, Kandeil MA. (2019). Nicorandil combats doxorubicin-induced nephrotoxicity via amendment of TLR4/P38 MAPK/NFj-B signaling pathway. Chemico-Biological Interactions 311, 108777.

Lawrence RA, Burk RF. (1976). Glutathione peroxidase activity in selenium- deficient rat liver. Biochemical and Biophysical Research Communications 71: 952-958.

Leng J, Li X, Tian H, Liu C, Guo Y, Zhang S, Chu Y, Li J, Wang Y, Zhang L. (2020). Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway. BMC Complementary Medicine and Therapies 20:126.

Marklund S, Marklund G. (1974). Involvement of superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry. 47: 469 - 474.

Micera M, Botto A, Geddo F, Antoniotti S, Bertea CM, Levi R, Gallo MP, Querio G (2020). Squalene: More than a Step toward Sterols. Antioxidants 9: 688.

Mohan M, Kamble S, Gadhi P, Kasture S. (2010). Protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats,. Food and Chemical Toxicology 48(1): 436–440, 2010.

Okokon J E, Ita BN, Udokpoh A.E. 2006. The in vivo antimalarial activities of Uvaria chamae and Hippocratea africana. Annals Trop Med Parasitol 100:585-590.

Okokon JE, Antia BS, Umoh EE, Etim EI. 2010. Antidiabetic and hypolipidaemic activities of Hippocratea africana. Int J Drug Dev Res 2: 501 -506.

Okokon JE, Nwafor PA, Charles U, Dar A, Choudhary MI. 2013a. The antioxidative burst and hepatoprotective effects of ethanolic root extract of Hippocratea africana against paracetamol-induced liver injury. Pharm Biol 51 (7):872 - 880.

Okokon JE, Dar A, Choudhary MI. 2013b. Immunomodulatory, cytotoxic and antileishmanial activities of Hippocratea africana. J Nat Pharmaceut 4 (2):81 – 85.

Okokon JE, Davies K, Okokon PJ, Antia BS. 2014. Depressant, anticonvulsant and antibacterial activities of Hippocratea africana. Int J Phytother 4 (3):144 – 153.

Okokon JE, Akpan HD, Ekaidem I, Umoh EE. 2011. Antiulcer and antidiarrheal activity of Hippocratea africana. Pak J Pharm Sci 24: 201- 205.

Okokon JE, Okokon PJ, Sahal D. 2017. In vitro antiplasmodial activity of some medicinal plants from Nigeria. Int J Herbal Med 5 (5):102-109.

Okokon JE, Chinyere CP, Bassey AL, Udobang JA. 2021. In vivo alpha amylase and alpha glucosidase activities of ethanol root extract and fractions of Hippocratea africana. South Asian J Parasitol 5(4): 42-48.

Okokon JE, Chinyere PC, Amaechi P, Bassey AL, Thomas PS (2022). Antioxidant, antidiabetic and hypolipidemic activities of ethanol root extract and fractions of Hippocratea africana. Tropical Journal of Natural Product Research. 6(3):446-453.

Olorundare OE, Adeneye AA, Akinsola AO, Sanni DA, Koketsu M, Mukhtar H. (2020). Clerodendrum volubile ethanol leaf extract: A potential antidote to doxorubicin-induced cardiotoxicity in rats. Journal of Toxicology 2020:n8859716.

Rajasekaran M. (2019). Nephroprotective effect of Costus pictus extract against doxorubicin-induced toxicity on Wistar rat. Bangladesh Journal of Pharmacology 14:93-100.

Raškovi A, Stilinovi N, Kolarovi J, Vasovi V, Vukmirovi S. (2011). The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats Molecules 16: 8601-8613

Rashid S, Ali N, Nafees S, Ahmad ST, Arjumand W, Hasan SK, Sultana S. (2013). Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicology Mechanisms and Methods 23: 337–345.

Rehman MU, Tahir M, Khan AQ, Khan R, Oday OH, Lateef A, Hassan SK, Rashid S, Ali N, Zeeshan M, Sultana S. (2014). D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX- 2, iNOS, and NFjB in kidneys of Wistar rats. Experimental Biology and Medicine (Maywood) 239:465–476.

Rhetso T, Shubharani R, Roopa MS, Sivaram V. (2020). Chemical constituents, antioxidant, and antimicrobial activity of Allium chinense G. Don. Future Journal of Pharmaceutical Sciences 6:102.

Sengupta S, Nandi I, Bhattacharyya DK, Ghosh M. (2018). Anti-Oxidant and anti-bacterial properties of 1-Octacosanol isolated from rice Bran Wax. Journal of Plant Biochemistry and Physiology 6: 206.

Sinha AK. (1972). Colorimetric assay of catalase. Analytical Biochemistry, 47: 389 - 94.

Tietz WW. (1990). Clinical Guide to Laboratory tests. 2nd edition. Sanders Company. Philadelphia, PA. pp. 554-556.

Umoh UF, Thomas PS, Essien EE, Okokon JE, De Leo M, Ajibesin KK, Flamini G, Eseyin OA. (2021). Isolation and characterization of bioactive xanthones from Hippocratea africana (Willd.) Loes.ex Engl. (Celastraceae). Journal of Ethnopharmacol. 280:114031.

Yilmaz S, Atessahin A, Sahna E, Karahan I, Ozer S. (2006) Protective effect of lycopene on adriamycin- induced nephrotoxicity and nephrotoxicity. Toxicology 218: 164-171.




DOI: https://doi.org/10.14421/biomedich.2023.122.477-484

Refbacks

  • There are currently no refbacks.


Bookmark and Share


Copyright (c) 2023 Kufre U. Noah, John A. Udobang, Jude E. Okokon, Martin O. Anagboso, Nwakaego Omonigho Ebong



Biology, Medicine, & Natural Product Chemistry
ISSN 2089-6514 (paper) - ISSN 2540-9328 (online)
Published by Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity.

CC BY NC
This work is licensed under a CC BY-NC