The Influence Of Acupuncture At Zusanli Acupoint On Pharmacokinetics Of Paracetamol

Objective: To investigate the effects of acupuncture at Zusanli acupoint on pharmacokinetics in rats after a oral paracetamol in single dose.Methods: 48 SD rats with half respectively male and female, weighing(250±20)g, were randomized into 6 equal groups, namely paracetamol low, moderate, high dosage groups(given orally paracetamol in single dose of 300,600,1200mg/kg by weight respectively),and acupuncture and paracetamol low, moderate, high dosage groups(acupuncture at Zusanli acupoint for 20 mins after giving orally paracetamol in single dose of 300,600,1200mg/kg by weight respectively).Whole blood samples were collected before (0h) and 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24h after oral administration of paracetamol. The concentrations of paracetamol in blood samples were determined by RP-HPLC, and the pharmacokinetic parameters were calculated by software 3P87, then the effects of acupuncture on pharmacokinetics in rats after oral paracetamol was observed.Results: In addition to that of acupuncture and APAP high dosage group was fitted to a nonlinear dynamic model, the plasma concentration-time curves of APAP of the other fives groups were all fitted to a two-compartment model with first order absorption in rats. Compared with the APAP low dosage group and APAP middle dosage group, the time of peak concentration(T_max) came ahead of time notablely(P<0.01), the peak plasma drug concentration(C_max) rose significantly(P<0.01),and the absorption half-life(T_1/2ka) speeded up apparently(P<0.01), but the elimination half-life(T_1/2ke) remained basically unchanged(P>0.05), and the area under the curve(AUC) increased significantly(P<0.01), but plasma clearance rate(Cl/F) lower notablely(P<0.01) in the acupuncture and APAP low dosage group and acupuncture and APAP middle dosage group. Compared with the APAP high dosage group, the AUC also increased significantly(P<0.01) and the mean residence time(MRT) postponed notablely(P<0.05) in the acupuncture and APAP high dosage group.Conclusion: Acupuncture at Zusanli can change absorption and metabolism of APAP in rats, the absorption speeds up apparently, the bioavailability increases significantly and the metabolism slowers notablely. The mechanisms of action are possible that acupuncture at Zusanli can increase plasma drug concentration in vivo by promoting gastrointestinal peristalsis and increasing gastric mucosal blood flow to enhance the absorption of paracetamol in gastrointestinal tract and improve its bioavailability. Objective: To investigate the effects of acupuncturing Zusanli acupoint on characteristics of related enzymes in metabolism of paracetamol in rats.Methods: 70 SD rats with half respectively male and female, weighing(230±20)g, were randomized into 7 equal groups, namely paracetamol low, moderate, high dosage groups(given orally paracetamol in single dose of 300,600,1200mg/kg by weight respectively),and acupuncture and paracetamol low, moderate, high dosage groups(acupuncture at Zusanli acupoint for 20 mins after giving orally paracetamol in single dose of 300,600,1200mg/kg by weight respectively), and the normal control group(given the same amount of saline). Then samples were collected to test different of biochemical indicators as follows: (1)the content of glutathione(GSH) and the activities of glutathione S-transferase(GST) in serum and liver homogenate; (2)the activaties of liver mitochondria Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase and SDH; (3)the activaties of liver microsomal Cyt.P450, Cyt.b5 and NADPH-cytochrome P450 reductase.Results: (1)Effects of acupuncturing Zusanli acupoint on GSH and GST:Acupuncture had no influence on the levels of GSH and GST in serum and liver with oral administration APAP at low dose of 300mg/kg(P>0.05). Acupuncture decrease the levels of GSH in serum and liver notablely with oral administration APAP at middle dose of 600mg/kg(P<0.05),and decrease the activaties of GST in liver notablely(P<0.05), but had no significant effect on the level of GST in serum (P>0.05). Acupuncture decreased the levels of GSH in serum and liver significantly with oral administration APAP at high dose of 1200mg/kg(P<0.01),and promoted the activaties of GST in serum(P<0.05) and decrease the activaties of GST in liver notablely(P<0.05).(2)Effects of acupuncturing Zusanli acupoint on hepatic energy metabolism enzymes: Acupuncture had no obvious effects on the activities of liver mitochondria Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase and SDH with oral administration APAP at low dose of 300mg/kg(P>0.05). Acupuncture inhibit the activities of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase and SDH significantly with oral administration APAP at middle dose of 600mg/kg (P<0.01 or P<0.05).Except for Ca²⁺-Mg²⁺-ATPase,acupuncture decreased the activities of Na⁺-K⁺-ATPase and SDH notablely with oral administration APAP at high dose of 1200mg/kg(P<0.01).(3)Effects of acupuncturing Zusanli acupoint on hepatic drug metabolism enzymes: Acupuncturing Zusanli had no significant influence on the contents of Cyt.P450 and Cyt.b5 and the activity of NADPH-cytochrome P450 reductase with oral administration APAP at doses of 300mg/kg,600mg/kg and 1200mg/kg(P>0.05).Conclusion: Acupuncturing Zusanli can cause the inhibitory action to GST and hepatic energy metabolism enzymes during the metabolism of APAP in rats,and the reason may be that acupuncturing Zusanli can increase the plasma concentrations of APAP by promoting absorption and increasing bioavailability of APAP. But acupuncturing Zusanli has no signignificant influence on the hepatic drug metabolism enzymes, the reason maybe have a ralation with that oxidative elimination of APAP by hepatic drug metabolism enzymes is not the main metabolic pathway of APAP. Objective:To observe the effects of acupuncture at Zusanli acupoint on serum transaminase and hepatic pathological changes in rats with given multiple doses of paracetamol.Methods: SD rats were divided into five groups, the NC group, the APAP₁ group and the ZC+APAP₁ group,the APAP₂ group and the ZC+APAP₂ group. The APAP₁ group and the APAP₂ group were given orally paracetamol in doses of 300 mg/kg and 600 mg/kg by weight respectively. The ZC+APAP₁ group and the ZC+APAP₂ group were acupunctured at Zusanli acupoint for 20 mins after giving orally paracetamol in dose of 300 mg/kg and 600 mg/kg by weight respectively. The NC group was given the same amount of saline. Each group was given paracetamol or saline once a day for 14 continuous days, and levels of serum AST,ALT and the pathological changes of liver tissues were observed.Results:Compared with the NC Group,the levels of serum AST,ALT were significantly increased in groups of ZC+APAP₁,APAP₂ and ZC+APAP₂(P<0.05 or P<0.01).Compared with the groups of APAP₁ andAPAP₂, the levels of serum AST,ALT were significantly increased in groups of ZC+APAP₁ and ZC+APAP₂(P<0.05 or P<0.01).There was no noticeable difference between the groups of APAP₁ and ZC+APAP₁(P>0.05), but significant difference between the groups of APAP₂ and ZC+APAP₂(P<0.05).Conclusion:Acupuncture at Zusanli can promote levels of serum AST,ALT induced by paracetamol,but the results of pathologic examination indicate that Acupuncture at Zusanli can ameliorate the pathological injure of liver.