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1.
Chinese Critical Care Medicine ; (12): 220-223, 2018.
Article in Chinese | WPRIM | ID: wpr-703627

ABSTRACT

Objective To explore the effect of sucralfate on cytokines in rats with paraquat (PQ) poisoning. Methods Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into PQ model group, sodium bicarbonate intervention group (SB group) and sucralfate suspension gel group (LTL group), with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL·kg-1·d-1of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline. The abdominal aortic blood of rats was collected at 1, 3, 6, and 10 days after PQ poisoning, and the levels of serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA). The left lung tissue was harvested, and lung wet/dry weight (W/D) ratio was assessed. Results With prolonged exposure, lung W/D ratios in all the groups were increased gradually, reached the peak at 10 days, but in the SB group and LTL group, the amplitude of increase was obviously reduced, the ratios were significantly decreased at 6 days and 10 days as compared with those in PQ model group (SB group vs. PQ model group: 4.99±0.79 vs. 6.98±0.86 at 6 days, 5.61±0.36 vs. 7.36±0.95 at 10 days; LTL group vs. PQ model group: 4.61±0.24 vs. 6.98±0.86 at 6 days, 4.24±0.20 vs. 7.36±0.95 at 10 days, all P < 0.05), but there was no significant difference between SB group and LTL group (all P > 0.05). After PQ poisoning, the levels of TNF-α, IL-10 and TGF-β1 were elevated, and reached the peak at 3 days and then decreased gradually. Compared with the PQ model group, serum TNF-α, IL-10 and TGF-β1 levels in SB group and LTL group were decreased significantly [SB group vs. PQ model group: 3-day TNF-α (ng/L) was 147.6±12.3 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 65.4±3.2 vs. 115.1±9.2, 3-day TGF-β1 (ng/L) was 356.3±50.3 vs. 415.6±68.3; LTL group vs. PQ model group: 3-day TNF-α (ng/L) was 82.2±7.4 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 44.4±5.2 vs.115.1±9.2, 3-day TGF-β1 (ng/L) was 296.3±40.2 vs. 415.6±68.3, all P < 0.05], especially in LTL group (all P < 0.05). Conclusion Early gastrointestinal lavage with sucralfate could effectively reduce the inflammatory exudation in lung tissue after PQ poisoning, and inhibit the cytokine secretion.

2.
Article in Chinese | WPRIM | ID: wpr-686678

ABSTRACT

Objective To observe the curative effect of continuous gastrointestinal decompression after gastric lavage with edible oil on saving patients with oral aluminum phosphide poisoning.Methods Seventy-eight patients with oral aluminum phosphide admitted to the Department of Internal Emergency of the Second People's Hospital of Yunnan Province from October 2009 to October 2016 were divided into a mild poisoning group (39 cases), a moderate poisoning group (26 cases) and a severe poisoning group (13 cases) according to clinical manifestations and laboratory examinations, all the patients were treated with continuous gastrointestinal decompression after early gastric lavage with edible oil, including scavenging toxicant, correcting intracellular oxygen intake and metabolic disturbance, and inhibiting and eliminating inflammatory mediators. The difference of remission times of clinical symptoms, recovery times of abnormal indexes and hospitalization times were compared among patients with different disease severities. Results With the aggravation of disease, the remission times of clinical symptoms (hours: from mild to severe were 24±12, 54±18, 84±12), recovery times of abnormal indexes (hours: from mild to severe were 18±6, 72±0, 108±12) and hospitalization times (hours: from mild to severe 48±24, 120±24, 144±24) were all gradually extended. Of the 13 patients with severe poisoning, 2 patients died of multiple organ functional failure (MOF) after 28 hours of treatment because they were incapable of cooperating with continuous gastrointestinal decompression. There were 76 patients were clinically cured, the cure rate being 97.4%. In the follow-ups at 1 month and 6 months after the treatment, no abnormalities were seen.Conclusion Continuous gastrointestinal decompression after early gastric lavage with edible oil for saving patients with oral aluminum phosphide poisoning is an effective therapy worthwhile to be popularized.

3.
China Pharmacy ; (12): 3932-3934, 2015.
Article in Chinese | WPRIM | ID: wpr-502678

ABSTRACT

OBJECTIVE:To study the effects of Tibetan medicine Zuotai on the activities of cytochrome oxidase (CYP1A2) and drug metabolism enzyme N-acetyltransferase 2(NAT2)in rats. METHODS:70 SD rats were equally randomized into a normal control (normal saline) group,the groups of single administration of low,middle and high-dose (1.2,3.8 and 12 mg/kg) Zuotai and the groups of multiple administrations thereof(once daily for 12 consecutive days). The rats were given drugs ig. caffeine(25 mg/kg)was given ig to the rats in the normal control group and the groups of single administration on the 2nd day,and to those in the groups of multiple administrations on the 13th day. 5 h later,their urine was collected and added with vitamin C based on 10 mg/ml. High performance liquid chromatography (HPLC) was adopted to determine the cafeine metabolites contents of 5-acetami-do-6-formamido-3-methyl-uric acid(AFMU),1-methylxanthine(1X),1-methyl-uric acid(1U)and 1,7-dimethyl uric acid(17U) in rats’urine,and the activities of CYP1A2 and NAT2 were reflected through (AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U). RESULTS:Compared with normal control group,the(AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U)in rats were de-creased,namely the activities of CYP1A2 and NAT2 were lower in the groups of single administration of middle-dose Zuotai and multiple administrations of middle and high-dose Zuotai than in the normal control group. There was statistical difference (P<0.05). CONCLUSIONS:Zuotai can obviously inhibit the activities of CYP1A2 and NAT2 in rats.

4.
Acta Pharmaceutica Sinica ; (12): 267-72, 2014.
Article in Chinese | WPRIM | ID: wpr-448732

ABSTRACT

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.

5.
Acta Pharmaceutica Sinica ; (12): 188-93, 2012.
Article in Chinese | WPRIM | ID: wpr-414953

ABSTRACT

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.

6.
Acta Pharmaceutica Sinica ; (12): 1117-22, 2011.
Article in Chinese | WPRIM | ID: wpr-414982

ABSTRACT

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.

7.
Article in Chinese | WPRIM | ID: wpr-580054

ABSTRACT

Objective To study the effect of Tibetan medicine Zuotai on in vivo pharmacokinetics of crocin-1 in rats.Methods After im injection of crocin-1 (5 mg/kg) in control (continuously ig normal saline for 7 d) and expermental (continuously ig Zuotai suspension for 7 d or 21 d) rats,The plasma concentration of crocin-1 was determined by RP-HPLC,and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters of crocin-1.Results After continuously ig administration of Zuotai [10 mg/(kg?d)] for 7 d and 12 d in experimental rats,the pharmacokinetic parameters of crocin-1 changed significantly.The AUC,Cmax,and MRT were significantly greater in experimental rats than those in control rats,and the CL and Vd were significantly lower than those in control rats,and the AUC of crocin-1 was greater in the 21 d administration group than that in the 7 d administration group.Conclusion The result demonstrates that Tibetan medicine significantly affects the pharmacokinetics of crocin-1 in rats.After administration of Zuotai in rats,the absorption degree of crocin-1 is significantly increased and the clearance rate is significantly decreased.

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