Toxicological evaluation of Picralima nitida in rodents.

Picralima nitida (Stapf) T. Durand and H. Durand (Apocynaceae), over the years has shown wide range of usage in African folk medicine and its safety profile in instances of prolonged use and pregnancy are major concerns. The study aimed to extensively investigate the toxicological effects of Picralima nitida in albino rodents and make appropriate extrapolations to humans. In the first phase of the experiment which evaluated the genotoxicity and subchronic toxicity of P. nitida, a total of 40 albino rats (male and female) were randomized into 4 groups of 10 animals per group. Group 1 (control group) was orally administered with 10 ml/kg of distilled water. Animals in Groups 2 to 4 were administered with aqueous seed extract of the plant at 100, 200, 400 mg/kg body weight/day, respectively. Oral administration at the designated doses was continued for 90 days after which they were sacrificed by cervical dislocation for subchronic toxicological assessment. In the genotoxicity phase, 30 female mice were randomized into 5 groups, the control group was treated with 10 ml/kg of distilled water, groups 2 to 4, treated with 100 mg/kg, 200 mg/kg and 400 mg/kg doses of extract, and the 5th group had cyclophosphamide (0.1 mg/kg). The mice were sacrificed on the 28th day for bone marrow sampling for genotoxicity testing. In the second phase of the experiment which evaluated the teratogenicity of P. nitida, graded doses of the extract were administered to pregnant rats from day 1-19. Three groups of 6 female rats per group were administered 75, 150 and 300 mg/kg aqueous extract of P. nitida and a fourth group of 6 rats used as control was administered distilled water at 10 ml/kg. On day 20, 3 dams from each group were sacrificed and the foetuses were harvested through abdominal incision for physical examination. The 3 remaining dams were allowed to litter. The litters were sacrificed at 6 weeks for biochemical, haematological and histological analyses. The LD50 determined was 707.107 mg/kg. The aqueous seed extract of P. nitida was found to be genotoxic at all the test doses. There were no significant alterations in haematologic and renal parameters following subchronic administration. Notable dynamics were observed in hormonal characteristics: there was a significant dose-dependent reduction in FSH while oestradiol and progesterone showed dose-dependent increase. Furthermore, P. nitida may cause hepatopathy as shown by hepatic venous and sinusoidal congestion on hepatic histology. Also, there is non-significant reduction in total cholesterol and LDL. No significant alteration in glucose level. Furthermore, the extract produced a statistically significant decrease in birth weight (p < 0.0001). The extract induced a significant (p < 0.05) increase in creatinine and transaminase levels in the first filial of group 150 mg/kg. The platelet count was increased in all treated group (p < 0.005). All the histology of kidney in 150 mg/kg group showed vascular congestion. In conclusion, the aqueous seed extract of P. nitida has teratogenic effects and should not be used in pregnant women. Also, P. nitida is highly genotoxic and may cause hepatic damage and depletion of glutathione pool on chronic use, thereby causing oxidative stress and its potential sequelae.