Aim: Many serious adverse effects of new xenobiotics are detected thorough toxicological studies. In this present study, the safety profile of C.articulata L. (Rutaceae) and M.aethiopicum (Celastraceae) leaf aqueous extracts was evaluated by acute and sub-chronic toxicity tests in male wistar rats.
Methods: Acute oral toxicity was investigated in 8 weeks old Swiss mice (18-24g) that were divided in 4 groups (n=4mice) given extract doses ranging from 7,500-12,000 mg/kg and 15,000-22,500 mg/kg for M.aethiopicum and C.articulata respectively.
In sub-chronic toxicity, male rats 8 weeks old weeks were divided into 8 groups (n=6). The two aqueous extracts were administered a single daily dose of 150, 300 and 450 mg/kg body weight orally for 21 consecutive days and at the 22th day, the organ weights, hematological, histological, serum biochemical parameters were determined.
Results: The LD50 of C.articulata and M. aethiopicum in Swiss mice were 18,985 mg/kg and 9,708 mg/kg body weight, respectively. General signs of toxicity due to large oral exposure to C.articulata were; hyper urination, diarrhea and hypo activity, while for M. aethiopicum were; Paralysis of hind limbs, defecation, respiratory distress, loss of balance and circling movement. Convulsions were observed in both extracts at death point. In the sub chronic toxicity test, no mortality was observed during the course of the entire study in rats treated with both extracts. Both extracts caused a dose dependent statistically significant reduction (p<0.001) in monocytes of the treatment groups. The dose of 150mg/kg of M.aethiopicum caused a significant increase (p<0.001) in Neutrophils, Eosinophils and Basophils. There was a statistically significant increase (p<0.05) in Haemoglobin, lymphocytes, Red blood cells, Hematocrit and Mean Packed Cell Volume at 450mg/kg dose of M.aethiopicum. In serum biochemical parameters both aqueous extracts caused a statistically significant reduction (p<0.05) in serum Alanine transferase enzyme. The aqueous extract of C.articulata caused a significant (p<0.01) dose dependent reduction on serum alkaline phosphatase enzyme and on plasma urea. M.aethiopicum caused a significant increase (p<0.01) in plasma Creatinine levels. There were no significant effects on Total bilirubin and Aspartate transferase with both extracts. There was a dose dependent increase in liver weight for both extracts with the highest of (32.83%, p<0.001) at dose of 450mg/kg of C.articulata. Histopathological examination revealed no significant patho- physiological changes in the kidney and intestines of the treatment -groups. However the higher dose (450mg/kg) of M.aethiopicum showed pneumonitis and edema of lungs, focal areas of hepatic and perivascular degenerations with lymphocytes infiltration of the liver tissues.
Conclusion: This study indicates that the LD50 values are above 5000mg/kg which is said to be experimentally safe for use under OECD guidelines. However prolonged use of higher doses of both extracts could result to Heamatological, biochemical and Histopathological changes in the living system , this implies the extracts potential to cause chronic toxicity.