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Sub-acute toxicity study on hydromethanolic leaves extract of Combretum hypopilinum (Combretaceae) Diels in Wistar rats

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Abstract

The plant Combretum hypopilinum Diels (Combretaceae) has been utilized in Nigeria and other African nations to treat many diseases including liver, inflammatory, gastrointestinal, respiratory, infectious diseases, epilepsy and many more. Pharmacological investigations have shown that the plant possesses anti-infective, antidiarrhoeal, hepatoprotective, anti-inflammatory, anticancer, sedative, antioxidant, and antiepileptic potentials. However, information on its toxicity profile is unavailable despite the plant's therapeutic potential. As such, this work aimed to determine the acute and sub-acute oral toxic effects of the hydromethanolic leaves extract of C. hypopilinum. The preliminary phytochemical evaluation was carried out based on standard procedures. The acute toxicity evaluation was conducted by oral administration of the extract at the dose of 5000 mg/kg based on the guideline of the Organization of Economic Co-operation and Development (OECD) 423. To investigate the sub-acute toxicity effects, the extract was administered orally to the animals daily for 28-consecutive days at the doses of 250, 500, and 1000 mg/kg. Mortality, body weight and relative organ weight were observed. The hepatic, renal, haematological, and lipid profile parameters were investigated. The liver, kidney, heart, lung, small intestine, and stomach were checked for any histopathological alterations. The results of the phytochemical investigation showed cardiac glycosides, tannins, steroids, flavonoids, alkaloids, saponins, and triterpenes. Based on the acute toxicity investigation outcome, no death and signs of toxic effects were observed. The result showed that the oral median lethal dose (LD50) of the extract was more than the 5000 mg/kg. The extract remarkably reduced the weekly body weight of the animals at 500 mg/kg in the first and second weeks. It also significantly decreased the relative kidney weight, alkaline phosphatase, glucose, potassium, and low-density lipoprotein. There was a remarkable elevation in the percentage of eosinophils, basophils, monocytes, and granulocyte. There were histopathological abnormalities on the kidney, lung, stomach, and small intestine. The extract is relatively safe on acute exposure but moderately toxic at higher doses on sub-acute administration, particularly to the kidney.

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Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AC:

Alveoli congestion

ALP:

Alkaline phosphatase

ALT:

Alanine transaminase

ANOVA:

Analysis of variance

AN:

Alveoli necrosis

AST:

Aspartate transaminase

CNS:

Central nervous system

CVS:

Cardiovascular diseases

EDTA:

Ethylenediaminetetraacetic acid

FDA:

Food and drug administration

GAE/g:

Gallic acid equivalent per gram of the extract

GC–MS:

Gas chromatography-mass spectrometry

HCT:

Haematocrit

HDL:

High-density lipoprotein

HMECH:

Hydro methanolic leaf extract of Combretum hypopilinum

HPLC:

High-performance liquid chromatography

IA:

Intestinal atrophy

KH:

Kupffer cell hyperplasia

LD50 :

Median lethal dose

LDL:

Low-density lipoprotein

MCH:

Mean corpuscular haemoglobin

MCHC:

Mean corpuscular haemoglobin concentration

MCV:

Mean corpuscular volume

MTN:

Moderate tubular necrosis

NA:

Normal alveoli

NF:

Normal features

NG:

Normal glomerulus

NH:

Normal features

NM:

Normal myocardium

NV:

Normal villi

NT:

Normal tubules

OECD:

Organization of economic cooperation and development

QEQ/g:

Quercetin equivalent per gram of the extract

RBC:

Red blood cells

ROW:

Relative organ weight

Rpm:

Revolution per minutes

SHN:

Slight hepatic necrosis

SN:

Slight mucosa necrosis

VA:

Villi atrophy

WBC:

White blood cells

WHO:

World Health Organization

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Acknowledgements

The authors are thankful to all staff of the Department of Pharmacology and Therapeutics, Ahmadu Bello University, Nigeria, for their support during this research. We are also thankful to all members of Pharmacy Scholars Initiative (PSI), a mentorship forum for their support. We appreciate the support of the University of Tasmania, Australia (via Studiosity) for the English language editing of the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria

    Mubarak Hussaini Ahmad, Abdulkadir Umar Zezi, Sherifat Bola Anafi & Sagir Mustapha

  2. College of Pharmacy, Riyadh Elm University, Riyadh, 11681, Saudi Arabia

    Omar Yahya Alshargi

  3. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Pulau Pinang, Malaysia

    Mustapha Mohammed

  4. Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria

    Mustapha Mohammed

  5. School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia

    Sagir Mustapha

  6. Department of Pharmacology, College of Medicine and Health Sciences, Federal University Dutse, Jigawa State, Nigeria

    Auwal Adam Bala

  7. Department of Pharmacology and Therapeutics, Bayero University Kano, Kano State, Nigeria

    Auwal Adam Bala, Sa’adatu Muhammad Julde & Abubakar Sadiq Wada

  8. Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, Nigeria

    Surajuddeen Muhammad

  9. School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tas, 7005, Australia

    Abubakar Ibrahim Jatau

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Contributions

MHA: Conceptualisation, Investigation, Data curation, Writing—Original Draft and editing. AUZ: Supervision, Project administration, Review, validation. SBA: Supervision, Project administration, Review, validation. OYA: Resource, Writing. MM: Formal analysis and Review. SM: Writing and Review. AAB: Writing and Review. SM: Resources and Review. SMJ: Resources, Writing—Review. ASW: Formal analysis. AIJ: Critically reviewed the whole manuscript. All the authors read and approved the final manuscript.

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Correspondence to Mubarak Hussaini Ahmad.

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Ahmad, M.H., Zezi, A.U., Anafi, S.B. et al. Sub-acute toxicity study on hydromethanolic leaves extract of Combretum hypopilinum (Combretaceae) Diels in Wistar rats. Toxicol Res. 38, 487–502 (2022). https://doi.org/10.1007/s43188-022-00133-5

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