Abstract

Piper capense Linn is a plant used in Cameroon to treat cancer and several other diseases such as urinary tract disorder, fever, stomach-ache and to improve appetite. The methanol extract of Piper capense has been reported for its antiproliferative activity towards several human cancer cell lines. The aim of this work was to evaluate the acute and subchronic oral toxicities of a methanol extract from P. capense fruits on rats. The acute oral toxicity assay was carried out by administration of a single dose of 5000 mg/kg body weight of methanol extract of the Piper capense to five female rats, after which the behavior of the animals and the number of deaths were noted after 48 h. The animals were then kept for observation for 14 days. On the 15th day, the rats were sacrificed and macroscopic observation of the organs was made. Concerning the subchronic toxicity study, the rats composed of males and females received three doses (250, 500 and 1000 mg/kg body weight/day) for a period of 28 days by oral gavage. General animal behavior, food intake, weight gain, organ weights, haematological parameters, serum, and urinary biochemical parameters, and histological sections of liver and kidneys, were evaluated. Methanol extract from the Piper capense fruits did not cause any death in rats that were administered a single dose of 5000 mg/kg body weight of extract and therefore, the letal dose 50 (LD50) of the extract is greater than 5000 mg/kg body weight. Subchronic administration of the methanol extract of Piper capense fruits showed significant variations (P > 0.05) after analysis of certain biochemical parameters: serum urea, urinary urea, alanine aminotransferase (ALAT), aspartate aminotransferase, (ASAT), serum protein; in both male and female rats that received the dose of 1000 mg/kg body weight/day. No major signs of toxicity were observed in the liver and kidneys of animals after analysis of the histological sections performed. Beside, some signs of toxicity were observed, including cell lysis and inflammation on the liver and kidney organs at a dose of 1000 mg/kg body weight/day. Finally, the methanol extract of Piper capense fruits is safe at lower doses, but could cause some damages at doses as high as 1000 mg/kg body weight/day. Consequently, it should be taken with caution when used in therapy.

Highlights

  • Secondary metabolites contained in plants due to their multiple biological activities are increasingly the preferred target in the scientific community's search for new and effective drug substances (Cowan, 1999)

  • During the acute toxicity study, there was no mortality recorded in animals after receiving a single dose of 5000 mg/kg body weight of P. capense fruit methanol extract

  • Based on the Organization for Economic Cooperation and Development (OECD) principle, it can be stated that the letal dose 50 (LD50) of the methanol extract from P. capense fruits is greater than 5000 mg/kg body weight

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Summary

Introduction

Secondary metabolites contained in plants due to their multiple biological activities are increasingly the preferred target in the scientific community's search for new and effective drug substances (Cowan, 1999). A methanol extract of the fruits has been reported to have a cytotoxic effect towards a panel of human cancer cell lines, including multidrug resistant phenotypes (Kuete et al, 2011, 2013). These cell lines included CCRF-CEM (IC50: 6.95 μg/mL), HL60 (IC50: 8.16 μg/mL), HL60AR (IC50: 11.22 μg/mL) and CEM/ADR5000 (IC50: 6.56 μg/mL) leukemia cell lines, MDA-MB231 (IC50: 4.17 μg/mL) and MDA-MB231/BCRP (IC50: 19.45 μg/mL) breast adenocarcinoma cell line, HCT116 p53þ/þ

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