|dc.description.abstract||Rapanea melanophloeos is a tropical tree that is extensively utilized in African traditional medicine to
treat helminthoses, tuberculosis and heart-water. It is also used as an expectorant, emetic, astringent,
as an anti-inflammatory agent; and it bears anthelmintic, molluscicidal, fungicidal, anticancer and
antimalarial activity. Despite its wide medicinal utilization, data and documentation of its adverse
effects or toxicity to humans and animals are scanty.
The present study examined the in vitro toxicity of the chlorofonnic and aqueous extracts of R.
melanophloeos bark to brine shrimp tArtemia salina), and the acute and sub-acute in vivo toxicity to
Sprague Dawley rats that were orally dosed, once daily with the aqueous and chloroformic extracts
for 56 and 28 days respectively.
The aqueous extract was found to have significant in vitro toxicity to brine shrimp with a median
lethal concentration (LCso) of 59.37 ug/ml, The chlorofonnic extract had no significant toxicity to
brine shrimp (LCso of 1250 ug/ml) at 24 hours post-exposure. Both the aqueous and chlorofonnic
extracts of R. melanophloeos were practically non toxic to rats (oral median lethal dose after single
dosing was above 7500 mg/kg). The aqueous extract demonstrated a no-observed-adverse-effect-level
(NOAEL)of 300 mg/kg and lowest-observed-adverse-effect-level(LOAEL) of 500 mg/kg; and the
chlorofonnic extract had a NOAEL of 500 mg/kg and a LOAEL of 1000 mg/kg. Transient clinical
signs of acute toxicity that included depression, inactivity, somnolence, delayed reaction to stimuli, lethargy and piloerection were less prolonged in rats dosed with the chloroformic extract. All the
animals recovered in 24 hours. Necropsy of the rats that died of the aqueous extract at 7500 mg/kg
revealed mucoid content in the lower gastrointestinal tract, modest congestion of the kidneys, general
congestion and modest enlargement of the liver and spleen. Histopathology revealed congestion of the
liver, lungs and kidneys.
Repeated doses of the aqueous extract at 1000 mg/kg for 56 days caused a significant increase in
organ weight indices of kidneys (p=0.008) and testis (p=O.015) compared to the controls. In contrast, the chloroformic extract significantly reduced weight gain of the rats at the same dosage (p<0. 000 1),
after administration for 28 days.
TIle results indicate that a dose of 1000mg/kg of the aqueous and chlorofonnic extracts of R.
melanophloeos caused a significant reduction in the WBC count from day 14 and remained so up to
day 56 and day 28 for the aqueous and chlorofonnic extract. The chlorofonnic extract caused a
significant increase in the red blood cell count and the hematocrit (p<O.OOOl)at the same dosage. In
comparison with the pre-treatment values, the red blood cell count, hematocrit, hemoglobin and
thrombocytes increased significantly in all dose groups at day 28 and day 56 (p<O.OOOl),while the
mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration decreased in animals
dosed with each extract (p<O.OOOl).
The aqueous extract caused a non dose-related significant increase in alkaline phosphatase activity at
all the dose levels (p=O.0034). Over time, and at all dose levels, there were elevations in alkaline
phosphatase and creatine kinase activity, and decreases in creatinine and aspartate aminotransferase in
rats dosed with each extract in comparison with pre-treatment readings. Increases in alanine
aminotransferase activity and blood urea nitrogen levels were particular to animals dosed with the
aqueous extract, while alanine aminotransferase activity decreased in animals dosed with the
chloroformic extract. No pathological lesions were observed at histopathology after prolonged oral
administration of the two extracts.
The extracts are slightly toxic to the liver and kidneys since they moderately altered the biochemical
parameters but did not induce detectable damage in these organs. The time-related changes in
parameters are largely due to changes in age over the experimental periods. These results
demonstrate that the polar and non polar extracts of R. melanophloeos have a wide margin of safety,
and R. melanophloeos can be safely utilized in traditional medicine.||en