Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers.

BACKGROUND: Mitragyna speciosa leaves have been abused by drug addicts as some of the alkaloids (mainly mitragynine) from the plant possess opiate and cocaine-like effects. These bring to its prohibition in Malaysia in 2004 as consumption of M. speciosa leaves has been perceived to lead to the abuse of other drugs such as cannabis and heroin. METHODS: In the current study, the in vitro and in vivo effects of M. speciosa methanolic, aqueous and total alkaloid leaves extracts on drug metabolizing enzymes, namely, cytochrome P450s (CYP450s) and UDP-glucuronosyl transferase (UGT) had been evaluated in rat liver cytosolic fraction and microsomes. Aminopyrine and p-nitrophenol (pNP) were employed as probe substrates in aminopyrine N-demethylase (APND) and UGT enzyme assays, respectively. Furthermore, mitragynine was also tested in vitro for its likelihood to inhibit APND and UGT activity. The assessment of the enzyme activity was conducted using spectrophotometric methods. RESULTS: In vitro, the IC50 value could only be obtained for the methanolic extract in APND study (595.30±30.78 µg/mL) and not in other studies due to the enzyme percentage inhibitions being <70%. In contrast to the in vitro study, the oral treatment of male Sprague-Dawley rats for 14 days with 50, 100 and 200 mg/kg of methanolic and aqueous extracts and with 5, 10 and 20 mg/kg of total alkaloid extract showed a profound increment on the APND and UGT activities. CONCLUSIONS: The current findings showed that possibilities exist for herb-drug interaction with increased clearance of drugs, which are primarily metabolized by CYP450s and UGT1A6 among M. speciosa leaves extract users.

Reversal of experimental ethanol-induced liver steatosis by borage oil.

The aim of study was to evaluate the hepatoprotective effect of borage oil containing predominantly gamma-linolenic acid in rats with alcoholic steatohepatitis. Liver of ethanol-treated animals was characterized by fatty and hydropic dystrophies. Liver triglyceride contents and activitiies of serum marker enzymes were significantly increased. Ethanol increased nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-induced chemiluminescence and the contents of liver thiobarbituric acid reactive substances (TBARS). The reduced glutathione content in the liver was decreased. Ethanol enhanced liver microsomal cytochrome P-450 (CYP450) content, aniline p-hydroxylase and amydopyrine-N-demethylase activities. The treatment with borage oil improved the liver morphology, decreased triglyceride contents and normalized serum marker enzyme activities. Borage oil developed an antioxidant effect in ethanol-treated rats. The treatment with this compound decreased NADPH-induced chemiluminescence and the content of lipid peroxidation products. Borage oil normalized CYP450 content compared with the ethanol-treated group. CYPI450 2E1 isoform is a main source of free oxygen radicals in the liver of ethanol-treated rats and we propose that the antioxidant effect of borage oil is realized via the normalization of CYP450 content and activities of CYP450-related microsomal oxidases, as borage oil can improve the lipid surrounding of CYP450. In our opinion, the hepatoprotection by borage oil in alcoholic steatosis is connected with its antioxidant properties.

Effects of Supplementation with a Schizandrin C Derivative DDB-mixed Preparation (DWP-04) on Antioxidant Activity in Cisplatin-induced Nephrotoxicity in Rats / 대한신장학회지

PURPOSE: This study investigated the effect of reducing cisplatin induced nephrotoxicity with DWP-04 that is the compound of Schizandrin C derivative biphenyldimethyl dicarboxylate (DDB), glutathione and selenium. For the purpose of observation is that how DWP-04 has influence on mechanism of reducing cisplatin induced nephrotoxicity with renal function test, free radical formation and detoxification enzyme system in renal tissue. METHODS: Five groups of rats were dosed with vehicle, cisplatin (2 mg/kg i.p.), cisplatin+DWP-04 (100, 200 mg/kg po), or cisplatin+sodium thiosulfate (200 mg/kg i.p.) daily for 4 weeks. RESULTS: Serum creatinine, lactate dehydrogenase and activity of hydroxy radical increased in the cisplatin group and suppressed in the cisplatin+DWP-04 group compared to the cisplatin group. The renal tissue concentration of lipid peroxidase and lipofuscin were increased in the cisplatin group compared to the other groups. The activity of aminopyrine N-demethylase, aniline hydroxylase, aldehyde oxidase and xanthine oxidase, of which free radical formation system in kidney was also decreased in the cisplatin+DWP-04 group compared to the cisplatin and cisplatin+sodium thiosulfate group. The activity of detoxification system of free radical, such as glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were markedly increased in the cisplatin+DWP-04 group than the cisplatin and the cisplatin+sodium thiosulfate group (p<0.05). CONCLUSION: It can be concluded that the mechanism of decreasing cisplatin-induced nephrotoxicity by DWP-04 is that the decreasing of the amount of lipid peroxide and lipofuscin in the renal tissue by increasing activity of the antioxidant defense system and the decreasing of reactive oxygen species by increasing detoxification enzyme activity.

[Effects of ethyl acetate extract of Semen Hoveniae on liver microsomal cytochrome P450 isoenzyme in rat].

OBJECTIVE: To investigate the effects of the ethyl acetate extract of Semen Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats. METHOD: The rats were given orally the ESH in the doses of 0.14, 0.17, 0.2 g x kg (equivalent to the crude herb) for 10 days respectively. Rat liver microsomal cytochrome P450, NADPH-Cyt C reductase, erythromycin N-demethylase (ERD), Aniline hydroxylase (ANH), aminopyrine N-demethylase (ADM) activities were quantitated by UV chromatography. The levels of mRNA expression of CYP1A1, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcripatase-polymerase chain reaction (RT-PCR). RESULT: The cytochrome P450 content, NADPH-Cyt C reductase activities and erythromycin N-demethylase (ERD) activities were not affected. Aniline hydroxylase (ANH) activities in liver were decreased by up to35.1%; aminopyrine N-demethylase (ADM) activitiesin liver were increased by up to 42.4%. The mRNA expression of CYP1A1, CYP2C11 and CYP3A1 were found to be increased markedly. CONCLUSION: A specific effect of ESH on liver microsomal cytochrome P450 isoenzyme in rats was observed in this investigation. ESH had various effects on liver microsomal cytochrome P450 isoenzyme.

Zinc mediates normalization of hepatic drug metabolizing enzymes in chlorpyrifos-induced toxicity.

The present study investigated the protective effects of zinc in attenuating the altered activities of drug metabolizing enzymes in the livers of rats intoxicated with chlorpyrifos. Male Sprague-Dawley rats received oral chlorpyrifos treatment (at a dose level of 13.5 mg/kg body weight in corn oil every alternate day), zinc supplementation alone (at a dose level of 227 mg/l in drinking water), or combined chlorpyrifos plus zinc treatments for a total duration of 8 weeks. The effects of different treatments were studied on the specific activities of various drug metabolizing enzymes including cytochrome P(450), cytochrome b(5), NADPH cytochrome-c-reductase, NADH cytochrome-c-reductase, aminopyrene-N-demethylase (APD) and aromatic hydrocarbon hydroxylase (AHH). Additionally, serum zinc levels were also determined in each of the treatment groups at the end of the study. Chlorpyrifos treatment resulted in a significant decrease in the serum zinc concentrations. Analogous to these changes, we observed significant depression in the activities of majority of the drug metabolizing enzymes investigated in the present study, except for AHH, where the decrease in enzyme activity was not statistically significant. However, zinc treatment to chlorpyrifos treated animals effectively restored the depressed serum zinc levels to within normal limits. Similarly, co-administration of zinc to chlorpyrifos intoxicated animals normalized the enzymatic activities of cytochrome P(450), NADPH cytochrome-c-reductase and NADH cytochrome-c-reductase within normal range. Collectively, these findings suggest that zinc plays an important role in regulating the hepatic activities of drug metabolizing enzymes in chlorpyrifos intoxicated animals, although it remains to be determined whether such protective effects of zinc are regulated directly, or through some indirect mechanism.

Effects of ethyl acetate extract of Semen Hoveniae on liver microsomal cytochrome P450 isoenzyme in rat / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of the ethyl acetate extract of Semen Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats.</p><p><b>METHOD</b>The rats were given orally the ESH in the doses of 0.14, 0.17, 0.2 g x kg (equivalent to the crude herb) for 10 days respectively. Rat liver microsomal cytochrome P450, NADPH-Cyt C reductase, erythromycin N-demethylase (ERD), Aniline hydroxylase (ANH), aminopyrine N-demethylase (ADM) activities were quantitated by UV chromatography. The levels of mRNA expression of CYP1A1, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcripatase-polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>The cytochrome P450 content, NADPH-Cyt C reductase activities and erythromycin N-demethylase (ERD) activities were not affected. Aniline hydroxylase (ANH) activities in liver were decreased by up to35.1%; aminopyrine N-demethylase (ADM) activitiesin liver were increased by up to 42.4%. The mRNA expression of CYP1A1, CYP2C11 and CYP3A1 were found to be increased markedly.</p><p><b>CONCLUSION</b>A specific effect of ESH on liver microsomal cytochrome P450 isoenzyme in rats was observed in this investigation. ESH had various effects on liver microsomal cytochrome P450 isoenzyme.</p>

Inhibition of drug metabolizing enzymes (cytochrome P450) in vitro as well as in vivo by Phyllanthus amarus SCHUM & THONN.

An alcoholic extract of Phyllanthus amarus (P. amarus) was found to inhibit cytochrome P450 (P450) enzymes both in vivo as well as in vitro. This was studied using specific resorufin derivatives, as substrate for isoenzymes in the P450 super family. Concentration needed for 50% inhibition of 7-ethoxyresorufin-O-deethylase (EROD), CYP1A1 was 4.6 microg/ml while concentration needed for 7-methoxyresorufin-O-demethylase (MROD) CYP1A2 was 7.725 microg/ml and 7-pentoxyresorufin-O-depentylase (PROD), CYP2B1/2 was found to be 4.18 microg/ml indicating that the extract inhibited the P450 enzymes at very low concentration. Extract also inhibited the activity of aniline hydroxylase (an indicator of CYP 2E1 activity, IC(50) 50 microg/ml) and aminopyrine demethylase (an indicator of CYP 1A, 2A 2B, 2D and 3A activity, IC(50) >1000 microg/ml). Oral administration of the extract was also found to reduce the elevated P450 enzyme activities produced by phenobarbitone by 50% at 250 mg/kg body weight. The implication of these results on the inhibition of carcinogenesis produced by the extract is discussed.

Herbal monoterpene alcohols inhibit propofol metabolism and prolong anesthesia time.

2,6-Diisopropylphenol (Propofol) is a short-acting intravenous anesthetic that is rapidly metabolized by glucuronidation and ring hydroxylation catalyzed by cytochrome P450. The goal of this research was to determine whether dietary monoterpene alcohols (MAs) could be used to prolong the anesthetic effect of propofol by inhibiting propofol metabolism in animals. Mice were injected intraperitoneally (i.p.) with MAs (100-200) mg/kg followed by the administration of 100 mg/kg propofol 40 min later via an i.p. injection. The time of the anesthesia of each mouse was recorded. It was found that (+/-)-borneol, (-)-carveol, trans-sobrerol, and menthol significantly extended the anesthetic effect of propofol (>3 times). The concentration of propofol in the mouse blood over time (up to 180 min) also increased in mice pre-treated with (-)-borneol, (-)-carveol, and trans-sobrerol. The volume of distribution of propofol decreased in the (-)-borneol (p<0.05), pre-treated group as compared to the propofol control group. Moreover, the maximum blood concentration of propofol and the concentration of propofol in the blood as indicated by the area under the curve were significantly increased in (-)-borneol and (-)-carveol pre-treated groups. Additional evidence using rat hepatocytes showed that (-)-borneol inhibited propofol glucuronidation whereas trans-sobrerol and (-)-carveol inhibited cytochrome P450 dependent microsomal aminopyrine N-demethylation. These results suggest that (-)-borneol extends propofol-induced anesthesia by inhibiting its glucuronidation in the mouse whereas trans-sobrerol (-)-carveol extends propofol-induced anesthesia by inhibiting P450 catalyzed propofol metabolism.

Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostachys japonicus.

The effects of methanol extract and gallic acid (3,4,5-trihydroxybenzoic acid) of Orostachys japonicus A. Berger on hepatic drug metabolizing enzymes and lipid peroxidation were investigated in rats treated with bromobenzene. The methanol extract of Orostachys japonicus reduced the activities of phase I enzymes, aminopyrine N-demethylase and aniline hydroxylase, that had been increased by i.p. injection of bromobenzene. Gallic acid isolated from Orostachys japonicus also reduced the aniline hydroxylase activity, while it did not affect the aminopyrine N-demethylase activity. The methanol extract and gallic acid restored the activity of epoxide hydrolase which had been decreased by bromobenzene. Hepatic glutathione content was lowered, along with increase in hepatic lipid peroxide, by bromobenzene administration. The hepatic lipid peroxidation induced by bromobenzene was prevented with the methanol extract and gallic acid of Orostachys japonicus. However, the decrease in glutathione was not altered by gallic acid. The present results suggest that the methanol extract and gallic acid of Orostachys japonicus may protect liver from bromobenzene toxicity through, at least in part, inhibiting the cytochrome P450-dependent monooxygenase activities and enhancing the activity of epoxide hydrolase. Antioxidant effect also may contribute to the protection of Orostachys japonicus against the bromobenzene-induced hepatotoxicity.

[Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum].

OBJECTIVE: To study the modulatory effect of Panax gingseng and coadministration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver. METHOD: Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase(APND), p-nitrophenol-hydroxylase(pNPH)activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR). RESULT: P. gingseng coadministrated with V. nigrum obviously decreased the P450 contents of liver microsomes, and the b5 contents. Both single and combined used inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, but combinative groups decreased the expression of CYP2C11. The combination of P. gingseng and V. nigrum induced the expression of CYP1A1. P. gingseng has inhibitory effect on CYP2B1/2 and inductive effect used with V. nigrum. The combination of P. gingseng with V. nigrum also induced the expression of CYP3A1. CONCLUSION: P. gingseng used singly has some different modulation effects compared with combinative used, which may occur because of drug-drug interaction based on cytochrome P450. To elucidate the drug-drug interaction, it needs further analysis and metabolism research.

Anti-hepatotoxic effects of Rosa rugosa root and its compound, rosamultin, in rats intoxicated with bromobenzene.

The effects of a methanol extract of Rosa rugosa root and its triterpenoid glycoside, rosamultin, on hepatic lipid peroxidation and drug-metabolizing enzymes were investigated in rats treated with bromobenzene. The methanol extract of R. rugosa root reduced the activities of aminopyrine N-demethylase and aniline hydroxylase, which had been increased by bromobenzene, but rosamultin did not affect the activities of the two enzymes. Both the methanol extract and rosamultin restored the activity of epoxide hydrolase, which had also been decreased by bromobenzene. Hepatic glutathione concentrations were lowered and hepatic lipid peroxides were increased in rats intoxicated with bromobenzene. The hepatic lipid peroxidation induced by bromobenzene was prevented with the methanol extract and rosamultin. However, the decrease in glutathione was not altered by the methanol extract of R. rugosa. These results suggest that the extract of R. rugosa and its compound, rosamultin, may protect against bromobenzene-induced hepatotoxicity through, at least in part, enhanced activity of epoxide hydrolase. Antioxidant properties may contribute to the protection of R. rugosa against bromobenzene-induced hepatotoxicity.

Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the modulatory effect of Panax gingseng and coadministration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver.</p><p><b>METHOD</b>Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase(APND), p-nitrophenol-hydroxylase(pNPH)activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR).</p><p><b>RESULT</b>P. gingseng coadministrated with V. nigrum obviously decreased the P450 contents of liver microsomes, and the b5 contents. Both single and combined used inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, but combinative groups decreased the expression of CYP2C11. The combination of P. gingseng and V. nigrum induced the expression of CYP1A1. P. gingseng has inhibitory effect on CYP2B1/2 and inductive effect used with V. nigrum. The combination of P. gingseng with V. nigrum also induced the expression of CYP3A1.</p><p><b>CONCLUSION</b>P. gingseng used singly has some different modulation effects compared with combinative used, which may occur because of drug-drug interaction based on cytochrome P450. To elucidate the drug-drug interaction, it needs further analysis and metabolism research.</p>

Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats.

AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on hepatic microsomal drug-metabolizing enzymes and liver function in rats. METHODS: TPs were administered intragastrically to rats at the doses of 833 mg.kg(-1).d(-1) (n=20) and 83.3 mg.kg(-1).d(-1) (n=20) respectively for six months. Controlled group (n=20) was given same volume of saline solution. Then the contents of cytochrome P450, b5, enzyme activities of aminopyrine N-demethylase (ADM), glutathione S-transferase (GST) and the biochemical liver function of serum were determined. RESULTS: The contents of cytochrome P450 and b5 in the livers of male rats in high dose groups (respectively 2.66 +/- 0.55, 10.43 +/- 2.78 nmol.mg MS pro(-1)) were significantly increased compared with the control group (1.08 +/- 1.04, 5.51 +/- 2.98 nmol.mg MS pro(-1); P<0.01, respectively). The enzymatic activities of ADM in the livers of female rats in high dose groups (0.91 +/- 0.08 mmol.mg MS pro(-1)min(-1)) were increased compared with the control group (0.82 +/- 0.08 mmol.mg MS pro(-1).min(-1); P<0.05). The GST activity was unchanged in all treated groups, and the function of liver was not obviously changed. CONCLUSION: The antidotal capability of rats' livers can be significantly improved after long-term consumption of TPs. There are differences in changes of drug-metabolizing enzymes between the sexes induced by TPs and normal condition.

Antioxidant activity of Smoke Shield in-vitro and in-vivo.

Smoke Shield is a proprietory formulation containing extract of turmeric (Curcuma longa), obtained by supercritical carbon dioxide gas extraction and post-supercritical hydroethanolic extraction, together with extracts of green tea and other spices whose presence synergistically increases the activity of turmeric. This study evaluates the antioxidant potentials of Smoke Shield in-vitro and in experimental animals, as well as in human models. Smoke Shield was found to scavenge superoxide radicals generated by photoreduction of riboflavin (50% inhibitory concentration = 91 microg mL(-1)) and hydroxyl radicals generated by Fenton reaction (50% inhibitory concentration = 95 microg mL(-1)) and reduced lipid peroxidation. Administration of Smoke Shield to mice was found to elevate antioxidant enzymes such as catalase and superoxide dismutase in blood as well as in liver and kidney. Glutathione-S-transferase activity was found to be significantly elevated in liver and kidney of animals treated with Smoke Shield. Glutathione levels were also significantly elevated in blood. Glutathione reductase was significantly elevated in kidney. Administration of Smoke Shield decreased the lipid peroxidation in serum, liver and kidney, as well as reduced the levels of conjugated dienes and hydroperoxides. Administration of Smoke Shield to smokers was found to increase the superoxide dismutase and glutathione in blood and decrease glutathione peroxidase. Smoke Shield inhibited phase I enzymes as represented by aniline-hydroxylase and aminopyrenedemethylase in-vitro. These results indicate that Smoke Shield has potent antioxidant activity, could inhibit phase I enzymes and increase detoxifying enzymes, which makes it an effective chemoprotective herbal formulation.

[Effects of Angelica sinensis polysaccharides on hepatic drug metabolism enzymes activities in mice].

OBJECTIVE: To study the effects of Angelica sinensis Polysaccharides (ASP) on the hepatic drug metabolism enzymes activities in normal mice and those prednisolone (PSL)-induced liver injury. METHOD: The activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method. RESULT: ASP increased the activities of glutathione S-transferase in liver microsomes and mitochondria. The cytochrome P450 content, NADPH-cytochrome c reductase, aminopyrine N-demethylase, and aniline hydroxylase activities in liver microsomes were also increased. PSL significantly increased serum ALT levels, and decreased the liver mitochondrial glutathione content. At the same time, other enzymes activities were all increased. When mice were treated with ASP 2.0 g.kg-1, the PSL-induced changes on cytochrome P450 enzymes, glutathione S-transferase, and GSH content were restored. CONCLUSION: ASP can modulate the activities of drug metabolism enzymes.

Effect of Korean Traditional Tea Materials Water Extract on Hepatic Oxygen Free Radical Generating and Scavenging Enzyme Activities in Lead Administered Rats

This study was designed to test the effect of Korean traditional tea materials on oxygen-free radical metabolism in lead (Pb) -administered rats. Male rats were divided into normal, Pb-control (Pb-Con) and Pb-water extract of green tea (Camellia sinensis; GT) , persimmon leaf (Diospyros kaki; PL) , safflower seed (Carhamus tinctorius: SS) , Du-Zhong (Eucommia ulmoides; EU) groups, respectively. Pb intoxication was induced by administration of lead acetate (25 mg/kg. B.W., oral) weekly. The extract was administered based on 1.26 g of raw material/kg B.W./day for 4 weeks. When the GT, PL, SS and EU were supplemented to the Pb-administered rats, hepatic lipid peroxide levels were significantly lower compared to the Pb-Con group. Hepatic cytochrom P-450 content and aminopyrine N-demethylase activity was lower in the Pb-Con group than in the normal group, whereas xanthine oxidase activity was significantly elevated in Pb-administered rats. The water extract of GT, PL, SS and EU supplementation attenuated changes in enzyme activities generating reactive oxygen species in the liver. Hepatic superoxide dismutase, catalase and glucose 6-phosphate dehydrogenase activities were significantly higher in the Pb-Con group than in the normal group, while monoamine oxidase activity also tended to increase in the Pb-administered rats. However, glutathione peroxidase and glutathione S-transferase activities, and glutathione content significantly decreased through Pb intoxication. The supplementation of GT, PL, SS and EU induced alleviation changes of hepatic antioxidant enzyme activity.

Effects of Angelica sinensis polysaccharides on hepatic drug metabolism enzymes activities in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Angelica sinensis Polysaccharides (ASP) on the hepatic drug metabolism enzymes activities in normal mice and those prednisolone (PSL)-induced liver injury.</p><p><b>METHOD</b>The activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method.</p><p><b>RESULT</b>ASP increased the activities of glutathione S-transferase in liver microsomes and mitochondria. The cytochrome P450 content, NADPH-cytochrome c reductase, aminopyrine N-demethylase, and aniline hydroxylase activities in liver microsomes were also increased. PSL significantly increased serum ALT levels, and decreased the liver mitochondrial glutathione content. At the same time, other enzymes activities were all increased. When mice were treated with ASP 2.0 g.kg-1, the PSL-induced changes on cytochrome P450 enzymes, glutathione S-transferase, and GSH content were restored.</p><p><b>CONCLUSION</b>ASP can modulate the activities of drug metabolism enzymes.</p>

Oestrogenicity and effect on hepatic metabolism of the aqueous extract of the leaf mixture of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis.

The aqueous extract of the leaf mixtures of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis given by oral route to immature female rats, at doses of 13, 49 and 94 mg/kg per day for 15 days induced a significant increase in ovarian and uteri weight as well as serum and ovarian oestradiol. Moreover, a significant decrease in liver of aminopyrine N-demethylase activity was noticed in treated animals.

[Some pathogenetic aspects of developing liver failure and preventing it in patients with liver cirrhosis after portosystemic shunting]. / Nekotorye patogeneticheskie aspekty razvitiia pechenochnoi nedostatochnosti i ee profilaktika u bol'nykh s tsirrozom pecheni posle portosistemnogo shuntirovaniia.

Patients with cirrhosis of the liver were found to have a considerable suppression of the system of biotransformation of the liver before operation which correlated with the data of the direct indices of monooxigenase system of hepatocytes--cytochrome P-450 and activity of N-demethylase of amidopyrine. Operative interventions on such patients independent of the type of portosystemic shunting result in considerably decreased content of metabolites of amidopyrine--4AAP and N-ac-4-APP in urine as compared with the preoperative level (p < 0.05). Hyperbaric oxygenation is the optimal stimulator of activity of the liver biotransformation system. Better indicators characterizing the increased metabolic activity of the liver were noted in patients with selective portosystemic anastomoses and hyperbaric oxygenation in the postoperative period.

Antioxidant activity of anti-inflammatory plant extracts.

The antioxidant properties of twenty medical herbs used in the traditional Mediterranean and Chinese medicine were studied. Extracts from Forsythia suspensa, Helichrysum italicum, Scrophularia auriculata, Inula viscosa, Coptis chinensis, Poria cocos and Scutellaria baicalensis had previously shown anti-inflammatory activity in different experimental models. Using free radical-generating systems H. italicum. I. viscosa and F. suspensa protected against enzymatic and non-enzymatic lipid peroxidation in model membranes and also showed scavenging property on the superoxide radical. All extracts were assayed at a concentration of 100 microg/ml. Most of the extracts were weak scavengers of the hydroxyl radical and C. chinensis and P. cocos exhibited the highest scavenging activity. Although S. baicalensis inhibited the lipid peroxidation in rat liver microsomes and red blood cells, the extract showed inhibitory actions on aminopyrine N-demethylase and xanthine oxidase activities as well as an pro-oxidant effect observed in the Fe3+-EDTA-H2O2 system. The results of the present work suggest that the anti-inflammatory activities of the same extracts could be explained, at least in part, by their antioxidant properties.