Chronic oral safety study of the aqueous extract of Combretum molle twigs on biochemical, haematological and antioxidant parameters of Wistar rats.

Combretum molle R.B/G. Don (Combretaceae) is a graceful deciduous shrub, distributed especially in tropical Africa and used in traditional medicine in the treatment of malaria, diabetes, and bacterial, liver and cardiovascular deseases. To our knowledge, no long-term toxicity studies of C. molle has ever been realized yet.The long-term toxicity study was conducted in accordance with OECD 408 guidelines with slight modifications. In fact, rats were divided in groups and treated orally with CMAE at doses of 62.5, 125 and 250 mg/kg for 6 months. The general behavior and signs of toxicity of the rats were daily observed. Body weight, food and water intake were recorded every 2 months for 6 months. At the end of treatment period, urine and blood samples were collected for hematological, biochemical and antioxidant estimations. Immediately, internal organs were collected and weighed.The results showed that no mortality and visible signs of the toxicity were recorded in all experimental animals. The administration of CMAE had no significant effects on body weight, organ weights, serum electrolyte, and food and water intake. However, all doses of CMAE produced an increase in high density lipoprotein cholesterol, white blood cells, platelets, glutathione, and a decrease in low density lipoprotein cholesterol and malondialdehyde rate. CMAE at doses of 125 and 250 mg/kg decreased in serum proteins and the activity of aspartate amino transferase, and increased the activity of catalase. In addition, CMAE (250 mg/kg) significantly decreased the alanine aminotransferase activity and the level of triglycerides, very low density cholesterol, total proteins and creatinine, and increased in renal clearance, red blood cells, hemoglobin, hematocrit and superoxide dismutase activity.At the end of this study, no signs of major intoxication was noted during 6 months of treatment. These results suggest that long-term consumption of CMAE at the therapeutic dose (250 mg/kg) presents low risks to human health.