Toxicological evaluations of combined administration of ethanolic stem bark extract of Enantia chlorantha and lisinopril in experimental type 2 diabetes

Abstract

Abstract Background Enantia chlorantha is a local medicinal plant commonly use in Nigeria for the treatment of diabetes but without support of scientific data. Large percentage of people suffering from diabetes who uses the plant as antidiabetic agent also combine its administration with standard antihypertensive drugs. Aim In the present study, we have investigated the possible toxicological effects of combined administration of E. chlorantha bark extract and lisinopril in diabetic model of experimental rats. Methods E. chlorantha stem bark was extracted by cold maceration of the pulverised stem bark in 70% ethanol. The acute toxicity effect of the plant was then evaluated in rats following oral administration of single dose of the extract. Diabetes was induced by intraperitoneal administration of 40 mg/kg streptozotocin into fructose fed rat. Diabetic rats were then randomly assigned into 6 groups of 7 rats each. One group was kept as the diabetic model while separate treatments were administered to the other six groups. Seven non diabetic rats were kept as the control group and administered normal saline. Results The LD50 of E. chlorantha stem bark was above 5000 mg/kg. Combined administration of lisinopril and E. chlorantha showed synergistic effects in the restoration of renal biomarkers (serum creatinine, urea, Na+ and K+), cardiac function biomarkers (CK-MB and LDH) and hematological parameters (RBC, WBC, HGB and PCV), while antagonistic effects were however observed with some of the liver biomarkers (AST, ALT, ALP, GGT, total protein and total bilirubin). Rats co-administered lisinopril and E. chlorantha also showed fatty liver with cholestasis. Conclusion The study concluded that diabetes is associated with kidney and cardiac dysfunction. Combined administration of lisinopril and E. chlorantha though may not aggravate these dysfunctions however, it may antagonize the efficacy of the plant in ameliorating liver dysfunction in diabetics.

Keywords

• Pharmacodynamics
• Drug-herb interaction
• Toxicity
• Liver function
• Diabetes