Evaluation of Antioxidants Supplementation on Renal, Hepatic and Cardiac Function Markers in Alloxan Induced Diabetes Mellitus Wister Rats

Main Article Content

Adline Erinma Ben-Chioma
Abiola Abubakar Sheudeen
Nwidum Leyiga Dornu
Ichebadu Isaac
Edna Ogechi Nwachuku
Aminayanate Mac Aworu
Ibioku Elekima


Aim: To evaluate antioxidants supplementation (selenium and vitamin E) on renal, hepatic and cardiac function markers in alloxan induced diabetes mellitus in Wister rats.

Study Design: Rats were randomly assigned into 5 groups with each group consisting of 5 rats. The treatment pattern involved the induction of hyperglycaemia in the rats followed by oral administration of selenium and vitamin E supplements singularly and in combination. The groups are as follow:

Group A: Alloxan induced diabetic Rats treated with selenium (0.02 mg/kg) for 35 days.

Group B: Alloxan induced diabetic Rats treated with Vitamin E (70.0 mg/kg) for 35 days.

Group C: Alloxan induced diabetic Ratstreated with both Selenium and Vitamin E (0.02 mg/kg + 70.0 mg/kg) for a period of 35 days.

Group D:  Alloxan induced diabetic Rats without any treatment (Positive control) for 35 days.

Group E: Rats in this group were fed normally for 35 days without induction and treatment (Negative control).

Place and Duration of the Study Area: The study was carried out in the Department of Medical Laboratory Science, Rivers State University, Port Harcourt, Nigeria over a period of 9 months (January, 2019 – September, 2019).

Methodology: After the inducement of hyperglycaemia in the rats (Group A – D) with a single dose intraperitoneal (IP) injection of 140mg/kg body weight of alloxan hydrate, treatment with the antioxidants (selenium and Vitamin E) was performed for 35 days. At the end of 35 days, the animals were allowed to fast for 18 hours and sacrificed. Plasma specimen collected was used for the assay of Na+, K+, HCO3, urea, creatinine, cardiac troponin I, LDH, AST, ALT, ALP, bilirubin, protein, albumin globulin and MDA while renal, hepatic and cardiac tissues collected were used for histological investigations.

Results: Significantly lower values were seen in Na+, K+, HCO3 and conjugated bilirubin in the diabetic rats without antioxidants supplementation (group D) when compared to diabetic rats with antioxidants supplementation of selenium and vitamin E (group A, B & C) and non-diabetic control group (group E). There were no significant differences seen when Group A, B, C and E were compared among one another. Also, significantly higher values were seen in AST, ALT, ALP, Unconjugated bilirubin, urea, creatinine, cardiac troponin I and MDA in the diabetic rats without antioxidants supplementation (group D) when compared with diabetic rats treated with antioxidants supplements of selenium and vitamin E (group A, B & C) and non-diabetic control group (group E). However, no significant differences were seen in LDH, total protein, albumin, globulin and total bilirubin at P=.05. Histological findings in the kidneys, liver and cardiac tissues of the rats treated with antioxidants supplement showed recovery tendencies compared to diabetic rats without antioxidant supplementation.

Conclusion: Results obtained suggest that the use of selenium or vitamin E singularly or in combination has ameliorative effect on cardiac, renal and hepatic function markers in alloxan-induced diabetic rats. However, the combination of selenium and vitamin E had no synergistic advantage over the use of selenium or vitamin E alone. 

Vitamin E, selenium, renal, hepatic, cardiac, diabetic, alloxan hydrate.

Article Details

How to Cite
Ben-Chioma, A. E., Sheudeen, A. A., Dornu, N. L., Isaac, I., Nwachuku, E. O., Aworu, A. M., & Elekima, I. (2020). Evaluation of Antioxidants Supplementation on Renal, Hepatic and Cardiac Function Markers in Alloxan Induced Diabetes Mellitus Wister Rats. Journal of Complementary and Alternative Medical Research, 9(3), 23-39. https://doi.org/10.9734/jocamr/2020/v9i330143
Original Research Article


Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464(7293):1293–300.

Chiang JL, Kirkman MS, Laffel LM, Peters AL. Type 1 diabetes through the life span: A position statement of the American Diabetes Association. Journal of Diabetes Care. 2014;37(7):2034–54.

Adeshara KA, Diwan AG, Tupe RS. Diabetes and complications: Cellular signaling pathways, current understanding and targeted therapies. Current Drug Target. 2016;17:1309-1328.

Luo X, Wu J, Jing S, Yan LJ. Hyperglycemic stress and carbon stress in diabetic glucotoxicity. Aging Diseases. 2016;7:90–110.

Zhou Y, Zhang W, Jia Q, Feng Z, Guo J, Han X, Liu Y, Shang H, Wang Y, Liu JW. High dose of vitamin E attenuates diabetic nephropathy via alleviation of autophagic stress. Front Physiology; 2019.
DOI: org/10.3389/fphys.2018.01939

Aksoy A, Karaoglu A, Akpolat N, Naziroglu M, Ozturk T, Karagoz K. Protective role of selenium and high doses of vitamin E against cisplatin-induced nephrotoxicity in rats. Asian Pacific Journal of Cancer Prevention. 2015;16(16):6877-6882.

El-Desoky EG, Abdelreheem M, Al-Othman MA, Alothman AZ, Mahmood M, Yusuf K. Potential hepatoprotecctive effects of vitamin E and selenium on hepatotoxicity induced by Malathion in rats. African Journal of Pharmacy & Pharmacology. 2012;6(11):806-813.

Yavus T, Altuntar I, Daliba N. Cardiotoxicity in rats induced by methidathion and ameliorating effect of vitamin E and C. Human & Experimental toxicity; 2004.
Doi: org/10.1191/0960327/04ht456oa

Ghlissi Z, Hakim A, Mnif H, Kallel R, Zeghal K, Boudawara T, Sahnoun Z. Effect of vitamin E on reversibility of renal function following discontinuation of coslistin in rats: histological and biochemical investigations. Saudi Journal of Kidney diseases & Transplantation. 2018;29:10-18.

Wang N, Tan H, Li S, Xu Y, Guo W, Feng Y. Supplementation of micronutrient selenium in metabolic diseases: Its role as an antioxidant. Hindawi oxidative Medicine and Cellular Pathology; 2017.
DOI: org/10.1155/2017/7478523

Bakker E, Gemke JBJR, Bokenkamp A. Endogenous markers for kidney function in children: A review. Clinical Reviews in Clinical Laboratory Sciences. 2018;55(3): 163-183.

Newman JD, Price PC. Nonprotein Nitrogen Metabolites. In: Burtis AC, Ashwood RE, Editors. Tietz Fundamentals of Clinical Chemistry. Philadelphia: Elsevier; 2003.

Schennellmann RG. Response of the Kidney. In: Klaassen CD, Watkins III SB. Editors. Casarett & Doull’s Essentials of Toxicology. 2nd ed. New York: McGraw Hill Lange; 2010.

Upadhyay RR. Emerging risk biomarkers in cardiovascular disease and disorders. Journal of Lipids. 2015;10:11-15.

Arjmand G, Farzard S, Marzieh MN, Abdullah A. Anthropometric indices and their relationship with coronary artery diseases. Health Scope. 2015;4(3):25-30.

Ukpabi JO, Uwanurochi K. Comparing indications for cardiovascular admissions into a Nigerian and Isreali hospital. Annals of African Medicine. 2017;16(2):70-73.

Jaeschke H, Naisbitt D. Immune mechasms in drug-induced liver injury. Drug-induced liver toxicity.
(Accessed 22 May 2019)
Available:https//link.springer.com/protocol/ 10.1007/978-1-4939-7677-5_25

Robert SM, Robert CJ, Franklin MR. Hepatooxicity: Toxic effects on the liver. In: Williams PL, James RC, Roberts SM, Editors. Principles of toxicology, environmental and industrial application. New York: Wiley-Interscience Publication; 2000.

Elekima I, Serakara GC. Toxicity induced haematological alterations after acute and chronic administration of tartrazine (E102) in albino rats. International Journal of Research and Reports in Hematology. 2019;2(3):1-17.

Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of Basic Clinical Pharmacology. 2016;7(2):27–31.

Patton CJ, Crounch SR. Spectrophometric and kinetic investigation of the Berthelot’s reaction for the determination of Amonnia. Analytical Chemistry. 1977;49(3):464-469.

Vaishya R, Arora S, Singh B, Mallika V. Modification of Jaffe’s kinetic method decreases bilirubin interference: A preliminary report. Indian Journal of Clinical Biochemistry. 2010;25(1):64–66.

Buck RP, Linder E. Recommendations for nomenclature of ion-selective electrode. Journal of Pure and Applied Chemistry. 1994;66(12):2527-2536.

Trinder P. Glucose measurement with enzymatic colorimetric methods. Annals of Clinical Biochemistry. 1969;6:24-25.

Kind PRN, King EJ. Estimation of plasma phosphatase by determination of hydrolysed phenol with amino antipyrine. Journal of Clinical Pathology. 1954;7:322-326.

Reitman S, Frankel S. Colorimetric estimation of serum transaminases. American Journal of Clinical Pathology. 1957;28(10):56–63.

Dangerfield GW, Finlayson R. Estimation of bilirubin in serum. Journal of Clinical Pathology. 1953;6:173

Engvall E, Perlmann P. Enzyme-linked Immunosorbent Assay (ELISA) quantitative assay of immunoglobulin G. Immunochemistry. 1971;8(9):871–874.

Ghosh PB, Mitra KH. A study on the methods of estimation of lactate dehydrogenase (LDH) activity in serum. Medical Experiment. 1963;8:28-34.

Henry RJ. Clinical chemistry, principles and Techniques. New York: Hoeber Medical, Harper-Row; 1964.

Speicher CE, Widish JR, Gaudot FJ, Helper BR. An evaluation of the overestimation of serum albumin by bromo-cresol green. American Journal of Clinical Pathology. 1978;69:347–350.

Busher JT. Serum albumin and globulin. In: Walter HK, Hall WD, Hurst JW, (editors). Clinical Methods: The history, physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990.

Prohp TP, Onoagbe IO. Plasma electrolyte concentrations in normal and streptozotocin-induced diabetic rats treated with extracts of Triplochiton scleroxylon K. Schum. American Journal of Research Communication. 2014;2:154-174.

Eteng MU, Ibekwe HA, Essien AD, Onyeama HP. Effects of Catharanthus roseus on electrolyte derangement induced by chiopropamide (Diabinese) on normoglycemic albino wistar rats. Journal of Bioresources. 2008;62:364-366.

Abdelhalim TA, Nur MN, Mansour S, Ibrahim A. Cardioprotective effect of vitamin E against myocardial infarction induced by Isoprenaline in albino rats. Asian Journal of Pharmaceutical and Clinical Research. 2018;11(6):273-276.

Helal GEE, Taba MN, Mohamed MA, Abu-Taleb MH. Ameliorative effect of vitamin E on oxidative stress induced by Bisphenol A in female albino rats. The Egyptians Journal of Hospital Medicine. 2016;65: 474-478.

Mardy B, Mohamed EF, Amin S, Rana S. Ameliorative effect of antioxidants (Vitamins C and E) against abamectin toxicity in liver, kidney and testis of male albino rats. The Journal of Basic & Applied Zoology. 2016;77:69-82.

Abdel-Samia AR, Bushra RR, Gomaa SMA. Cardio-protective effect of vitamin E on doxorubicin-induced cardiotoxicity in adult male albino rats: A histological and biochemical study. The Egyptian Journal of Histology. 2019;42(1):147–161.

Ben-Chioma EA, Elekima I. Evaluation of Vitamin E and Selenium levels in breast cancer patients in Port Harcourt metropolis, Nigeria. Journal of Advances in Medicine and Medical Research. 2018;28 (2):1-7.