Effects of the dried-stem powder of cissus quadrangularis on hepatic cytochrome P450 and clinical blood chemistry in rats

Abstract

Cissus quadrangularis Linn., known locally as "Phet-Cha-Sung-Khat" is considered to be a folk medicine for bone healing and antihemorrhoid. It is a plant in family vitaceae. In this study. effects of the dried-stem powder of cissuss quadrangularis on phase I hepatic cytochrome P450 (CYP) involving in drug metabolism and carcinogenic/mutagenic bioactivation such as CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A were examined in rats. Effects of this compound on clinical blood chemistry and hematology were also determined. Male wistar rats were randomly divided into 3 groups of 10 rats each. Control group was given distilled water orally at 1 ml/kg/day whereas the other two groups received the dried-stem powder of cissus quadrangularis orally at dosages of 0.03 g/kg/day, respectively, for 30 consecutive days. During the experimental period, body weight, food and water intake were recorded every week. At the end of the experimental period, rats were anesthesized. Blood samples were collected by heart puncture and serum was prepared for determining hematology and clinical blood chemistry, respectively. Microsomes were prepared from livers for enzyme assays. The results demonstrated that there were no significant differences of body weight, food and water consumption between cissuss quadrangularis treated groups and the control group. C. quadrangularis at the dosages of either 0.03 or 0.3 g/kg/day did not cause any significant changes of hepatic microsomal total CYP contents as well as the activities of CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A. Furthermore, both dosage regimens of c. quadrangularis did not affect these following clinical blood chemistry and hematology parameters: AST, ALT, ALP, total billirubin, direct billirubin, BUN, SCr, uric acid, total cholesterol, TG, LDL-C, HDL-C, glucose, sodium, potassium, chloride, hemoglobin, hematocrit, MCV, MCH, MCHC, RBC count, platelet count, WBC count , % differential WBCs and RBC morphology. Results from this study indicate the safety from drug-drug interaction when c. quadrangularis is used concomitantly with other medicines which are metabolized by these CYPs. In addition, possibilities of this plant to increase and/or decrease risks of toxicity, mutagenicity and carcinogenicity induced by xenobiotics which are bioactivated by these CYP isoforms, were excluded. Furthermore, dried-stem powder of c. quadrangularis at the doses given in this study did not produce any toxic effects on several important organs/systems such as liver, kidney, blood system, electrolytes as well as lipid and carbohydrate metabolism.