Subchronic effects of barakol on hepatic cytochrome P450 and blood clinical biochemistry parameters in normal and high cholesterol diet rats

Abstract

Barakol is a major constituent extracted from flowers and young leaves of Cassia siamea Lam. This study examined subchronic effects of barakol on phase I hepatic cytochrome P450 (CYP) involving carcinogenic bioactivation such as CYP1A1, CYP1A2, CYP2B1/2B2 and CYP2E1 as well as phase II detoxification enzyme, GST, in rats fed normal or high cholesterol diet. Effects of this compound on blood clinical biochemistry parameters and hematology were also determined. Thirty-two male Wistar rats were randomly divided into 4 treatment groups. Rats in first and second groups were fed normal diet and high cholesterol diet, respectively, serving as control groups. The other two groups of rats were given barakol orally at a dosage of 30 mg/kg/day for 90 days and fed normal or high cholesterol diet. At the end of the treatment period, rats were anesthesized. Blood was collected by heart puncture and serum was prepared for measuring hematology and clinical biochemistry parameters, respectively. Microsomes and cytosols were prepared from livers for enzyme assays. The results showed that barakol significantly decreased CYP1A2 activity in both normal and high cholesterol conditions and significantly inhibited CYP1A1 activity in high cholesterol diet group. No changes of CYP2B1/2B2, CYP2E1 and GST activities were observed. The inhibitory effect of barakol on CYP1A1 and CYP1A2 may partly explain its animutagenic/anticarcinogenic effects of young C. siamea leaves on chemical-induced mutagenesis/carcinogenesis. For blood clinical biochemistry parameters, normal and high cholesterol diet rats treated with barakol demonstrated a significant decrease of TG but an increase of total and direct bilirubin comparing to their corresponding diet control groups. Normal diet rats treated with barakol showed no changes of these following parameters: SGOT, SGPT, ALP, BUN, SCr, total cholesterol, LDL-C, HDL-C, LDL-C/HDL-C ratio, serum glucose, Hb, Hct, platelet count, WBC count, and % differential WBCs. Cholesterol feeding increased some blood clinical biochemistry parameters such as SGOT, SGPT, ALP, total cholesterol, LDL-C and LDL-C/HDL-C ratio, but had no effect on total and direct bilirubin. High cholesterol diet rats administered with barakol showed a significant decrease of ALP comparing to the correponding high cholesterol diet group. These findings were conceivable that either high cholesterol diet or barakol administration caused a liver injury but in the different manner. Further studies on the effects of various doses of barakol on hepatic drug metabolizing enzymes and on blood clinical biochemistry parameters as well as the mechanism of which barakol induced liver injury were suggested.