Toxicity assessment of sub-acute and sub-chronic oral administration and diuretic potential of aqueous extract of Hibiscus sabdariffa calyces

N S Njinga; A T Kola-Mustapha; A L Quadri; O Atolani; R O Ayanniyi; M O Buhari; T O Amusa; E O Ajani; O O Folaranmi; M T Bakare-Odunola; L Kambizi; A T Oladiji; P Ebong

doi:10.1016/j.heliyon.2020.e04853

Toxicity assessment of sub-acute and sub-chronic oral administration and diuretic potential of aqueous extract of Hibiscus sabdariffa calyces

Heliyon. 2020 Sep 21;6(9):e04853. doi: 10.1016/j.heliyon.2020.e04853. eCollection 2020 Sep.

Authors

N S Njinga^{1

2}, A T Kola-Mustapha^{1

3}, A L Quadri^{1

4}, O Atolani^{1

5}, R O Ayanniyi⁶, M O Buhari⁷, T O Amusa^{1

8}, E O Ajani^{1

9}, O O Folaranmi⁷, M T Bakare-Odunola^{1

2}, L Kambizi^{1

10}, A T Oladiji^{1

4}, P Ebong^{1

11}

Affiliations

¹ African Centre for Herbal Research Ilorin (ACHRI), Central Research Laboratories, University of Ilorin, Ilorin, Nigeria.
² Department of Pharmaceutical and Medicinal Chemistry, University of Ilorin, Ilorin, Nigeria.
³ Department of Pharmaceutics and Industrial Pharmacy, University of Ilorin, Ilorin, Nigeria.
⁴ Department of Biochemistry, University of Ilorin, Ilorin, Nigeria.
⁵ Department of Chemistry, University of Ilorin, Ilorin, Nigeria.
⁶ Department of Pharmacology and Toxicology, University of Ilorin, Ilorin, Nigeria.
⁷ Department of Pathology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
⁸ Department of Forest Resources Management, University of Ilorin, Ilorin, Nigeria.
⁹ Kwara State University Malete, Ilorin, Nigeria.
¹⁰ Department of Horticulture, Cape Peninsula University of Technology, South Africa.
¹¹ Department of Biochemistry, University of Calabar, Calabar, Nigeria.

Abstract

Background: Food and herbal usage of Hibiscus sabdariffa (HS) is attaining improved global relevance and acceptance without recourse to its potential toxic effects. This study investigated the safety profile of acute, sub-acute, sub-chronic administrations and diuretic potential of aqueous extract of Hibiscus sabdariffa calyces (AEHSC).

Method: Acute oral toxicity, sub-acute and sub-chronic toxicity as well as diuretic studies were carried out on HS. A total of 20 Wistar rats were used for each toxicity study and assigned into four groups of five rats. The extract was administered as a single daily dose of 125, 250 and 500 mg/kg body weight (bwt) for 28 and 90 days respectively. To evaluate diuretic activity, 25 rats were divided into five groups of five rats and administered normal saline, hydrochlorothiazide 10 mg/kg, AEHSC 67.5, 125 and 250 mg/kg via the oral route. Urine sample was collected after 18 h, volume measured and concentration of electrolytes analyzed. The hematological and biochemical parameters were evaluated as well as the histopathology of kidney and liver.

Results: The acute oral toxicity was found to be >2000 mg/kg. AEHSC did not alter concentration of WBC, MCV, MCHC, lymphocyte as well as total and direct bilirubin in the sub-acute study. However, AEHSC significantly (p < 0.05) increased total protein, albumin, globulin, Na⁺, Cl^-, HCO₃ ^- and platelet levels, while levels of uric acid, creatinine, K⁺, RBC, Hb, total cholesterol, triglycerides, LDL-C, HDL-C and atherogenic index were decreased significantly (p < 0.05). In the sub-chronic study, AEHSC significantly (p < 0.05) increased the levels of globulin, urea, creatinine, MCH and atherogenic index. The concentrations of uric acid, WBC, platelets and HDL-C were significantly (p < 0.05) decreased. In both the sub-acute and sub-chronic studies, activities of ALP, ALT, AST, GGT and LDH in selected organs were altered without significant increase (P < 0.05) in activity of these enzymes in the serum. The AEHSC at all the doses showed remarkable diuretic activity during 18 h period comparable to hydrochlorothiazide. The extract also showed a non-dose-dependent increase in excretion of electrolytes. Histological analysis of sections of the liver and kidney for both sub-acute and sub-chronic studies showed normal histology comparable to the control group.

Conclusion: This study revealed AEHSC has some toxic effects in rats on sub-chronic administration. In addition, the extracts produced a significant diuretic activity. Hence, prolonged oral consumption of the extract may not be recommended.

Keywords: Chemical characterization of food; Chemical composition of food; Diuretic; Dose-response relationship; Drug development; Food toxicology; Haematology; Hibiscus sabdariffa; Natural product; Pharmacology; Plant products; Sub-acute; Sub-chronic; Toxicity; Toxicology.