[Assay of flow cytometry for the effect of cepharanthine on resistance to doxorubicin].

The biochemical activity of cepharanthine and the possible mechanism by which it reverses the resistance to doxorubicin in P388 leukemia cells were examined in vitro. The microfluorometric analysis of the cellular level of doxorubicin in drug-resistant cells showed that cepharanthine markedly enhanced the sensitivity of doxorubicin against resistant cells in the cellular level. Cepharanthine also enhanced the inhibitory effect of doxorubicin on the incorporation of thymidine into DNA in resistant cells.

Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium.

The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.

Inhibition of hepatic drug biotransformation by carrageenan-induced inflammation in the rat: effect of sex hormone alterations.

Following in vivo treatment with carrageenan, sex-related differences in alteration of hepatic drug metabolism were found in the rat. In adult male rats, marked decreases were observed in hepatic 9000 x g supernatant cytochrome P-450 content and in the biotransformation of hexobarbital, aminopyrine, ethylmorphine, and meperidine. Hexobarbital hypnosis was significantly prolonged by carrageenan treatment in intact and testectomized animals as compared to their respective controls.

Sustained release of 5-fluorouracil from oil/water emulsions.

Release profile of 5-fluorouracil (5-FU) from O/W emulsion and bone marrow toxicity of 5-FU to mice were compared with those of an aqueous solution of 5-FU. 5-FU emulsion had lower bone marrow toxicity and a slower drug release rate than the 5-FU aqueous solution which exhibited high bone marrow toxicity and fast drug release rate. A correlation between the rate of drug release and bone marrow toxicity was suggested.

Effect of carrageenan-induced inflammation on the induction of hepatic microsomal enzymes by phenobarbital and benzo[a]pyrene in male rats.

The inhibitory effect of carrageenan-induced inflammation was examined by utilizing rats treated with inducers of this drug metabolizing system. Animals were given sodium phenobarbital (PB, 80 mg/kg, i.p.

[The depression of hepatic drug-metabolizing enzyme activity in rats with carrageenan-induced inflammation. II. The effect on the status of plasma antipyrine concentration in rats].

The variation of hepatic drug-metabolism was investigated in male Wistar rats bearing hind paw edema induced by carrageenan (1%, 0.1 ml, s.c.

Interaction of doxapram and pentobarbital in mice.

We found a statistically significant increase in duration of pentobarbital-induced narcosis in doxapram-treated mice. The influence of doxapram (a respiratory stimulant) pretreatment on pentobarbital metabolism in mice was assessed by measurements of sleeping times, hypothermia, LD50 values, hepatic microsomal metabolism and relative plasma and brain levels of pentobarbital. When doxapram was given intraperitoneally 60 min.

Purification and characterization of beta-galactoside binding lectin from frog (Rana catesbeiana) eggs.

A beta-galactoside-binding lectin, a homodimer composed of 14kDa subunits, was purified from unfertilized eggs of the frog Rana catesbeiana by asialofetuin-Sepharose 4B affinity column chromatography. The lectin was solubilized from eggs by addition of neither haptenic sugar nor detergent and showed a unique characteristic that it requires neither Ca++ nor SH-reagent for its hemagglutination activity. However, the partial amino acid sequence indicated that the lectin belongs to a family of soluble 14kDa beta-galactoside-binding lectins (14K-lectin) widely distributed in vertebrates and classified as S type lectins.

[Modulation of anthracycline resistance by reserpine in P388 leukemia cells].

The activity of reserpine and a possible mechanism by which it reverses the resistance to both doxorubicin and pirarubicin in doxorubicin-resistant P388 leukemia (P388/DOX) cells were examined in vitro. During 48 hr drug-exposure, the sensitivity of doxorubicin and pirarubicin were potentiated markedly when reserpine was present at the concentration of 1 microgram/ml, which is not toxic to P388 leukemia (P388/S) cells. However, reserpine had little effect on the cytotoxicity of doxorubicin and pirarubicin in the sensitive parent cell.

Effect of sodium chloride on pirarubicin induced cell killing in P388 mouse leukemia cells.

The effect of sodium chloride on the cytotoxicity of 4'-O-tetrahydropyranyldoxorubicin (pirarubicin), a novel anthracycline derivative, was investigated on P388 mouse leukemia cells in vitro. The modifications in efficiency of uptake and killing action of pirarubicin were found to be dependent on the ionic strength of the medium. The relationship between intracellular drug accumulation into cells and cell killing was pointed out.

Exacerbation of doxorubicin toxicity by chlorpromazine in male ddY mice.

We examined whether chlorpromazine (CPZ) modulates the lethality of doxorubicin (DOX, 12 mg/kg, i.p.) in mice treated with CPZ (6 mg/kg, i.

Doxapram inhibits the in vitro oxidation of hexobarbital.

The effect of doxapram on the mouse liver microsomal hexobarbital metabolism in vitro was studied. Doxapram inhibited hexobarbital oxidase in a competitive manner, with inhibition constants between 2 and 10 mM. Doxapram induced a reverse type I spectral change with a spectral dissociation constant of about 0.

Drug interaction effects on antitumour drugs (X): exacerbation of cisplatin lethality by bacterial lipopolysaccharide in mice.

To determine whether bacterial endotoxin (lipopolysaccharide, LPS from Escherichia coli) could modulate the lethality of cisplatin (CDDP) in mice, animals were treated with LPS (1 mg/kg, intraperitoneally) 24 hr and 1 hr before administration of cisplatin. A 1.6-fold increase in 8-day cumulative mortality was observed in LPS-treated mice compared to the mortality of those injected with saline before CDDP administration.

Comparative base specificity, stability, and lectin activity of two lectins from eggs of Rana catesbeiana and R. japonica and liver ribonuclease from R. catesbeiana.

Two lectins with RNase activity obtained from eggs of Rana catesbeiana and R. japonica and RNase obtained from R. catesbeiana liver show 65-83% protein homology.

Induction of hepatic cytochrome P-450 and drug metabolism by doxapram in the mouse.

The ability of doxapram (20 mg/kg, i.p. daily for 5 days) to induce hepatic cytochrome P-450 and xenobiotic metabolism was examined in male mice.

Influence of chlorpromazine on the toxicity of pirarubicin in mice.

The influence of chlorpromazine (CPZ) on the toxicity of pirarubicin (THP) was examined in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by THP. These results demonstrate that that in vivo combination of THP and CPZ at high doses will result in an increase of toxicity in mice.

Endotoxin- and inflammation-induced depression of the hepatic drug metabolism in rats.

Carrageenan-induced inflammation and exposure to endotoxin considerably decreased the content of cytochrome P-450 and activities of ethylmorphine N-demethylase and meperidine N-demethylase, but did not decrease the activities of aniline hydroxylase or NADPH-cytochrome c reductase, compared with the respective activities in rats treated with carrageenan alone. These results suggest that under these experimental conditions, the two host-related environmental factors interact and enhance a decrease in rat hepatic microsomal drug metabolizing enzymes depending on the substrate used.

Perturbation of metabolism and disposition of cyclophosphamide by interferon and poly I:C, an interferon inducer, in mice.

The effects of interferon and poly I:C on the metabolism and disposition of cyclophosphamide were investigated in mice. Elimination of cyclophosphamide from the blood was decreased in mice treated 24 hr previously with interferon (2.5 x 10(6) U/kg, intraperitoneally) or poly I:C (10 mg/kg, intraperitoneally).

Effect of chlorpromazine on the toxicity of doxorubicin in mice.

The effect of chlorpromazine (CPZ) on the toxicity of doxorubicin (DOX) were investigated in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by DOX. These results suggest the potentiation of DOX toxicity by CPZ is due to increase of sensitivity of mice to DOX.

Potentiation of pirarubicin cytotoxicity by dipyridamole in doxorubicin-resistant mouse P388 leukemia cells.

The activity of dipyridamole and its possible mechanisms which reverse the resistance of pirarubicin were studied in a P388 mouse leukemia cell lines. Dipyridamole alone was minimally cytotoxic in both of the doxorubicin-resistant cell line (P388/DOX) and the sensitive parent cell line (P388/S), but reversed pirarubicin-resistance in a dose-related manner in P388/DOX cells. A similar dose-response relationship was observed for dipyridamole by increasing net intracellular pirarubicin accumulation.

Hepatic drug metabolizing activity in rats with carrageenan-induced inflammation.

Effect of carrageenan-induced inflammation on hepatic drug metabolism was studied in male and female Wistar rats. One day after treatment of male and female Wistar rats with carrageenan (1%, 0.1 ml, s.

Preliminary evidence for bacterial endotoxin therapeutics of paraquat lethality in mice.

In mice treated with endotoxin (LPS) extracted from Escherichia coli (1 mg/kg, i.p.), 3 hr after paraquat (70 mg/kg, i.

Effect of cepharanthine on doxorubicin cytotoxicity in P388 murine leukemia cells in vitro and in vivo.

The effect of cepharanthine on the cytotoxicity of doxorubicin (DOX) in p388 leukemia cells was studied in vitro and in vivo. Nontoxic levels of cepharanthine enhanced the sensitivity to doxorubicin in p388 cells in vitro. The potentiation of antitumor activity of DOX by cepharanthine against mice bearing p388 cells was also observed.

Preventive effects of a Chinese herb medicine (sho-saiko-to) against lethality after recombinant human tumor necrosis factor administration in mice.

We observed the effects of a chinese herb medicine Sho-saiko-to on the lethal and antitumor activities of recombinant human tumor necrosis factor (rhTNF) administered in mice. Sho-saiko-to was noted to protect the rhTNF-induced lethality in galactosamine-hypersensitized mice, and also Sho-saiko-to pretreated mice was protected against the decrease of rectal temperature after rhTNF administration. On the other hand, there was a remarkable enhancement of antitumor activity of rhTNF by Sho-saiko-to pretreatment.

Drug interaction effects on antitumour drugs (VIII): prevention of ifosfamide-induced urotoxicity by disulfiram and its effect on antitumour activity and acute toxicity of alkylating agents in mice.

To reduce the side-effects and to enhance the antitumour activities of antitumour agents, we have been investigating their combined use with routine drugs. In the present study, we examined the effects of disulfiram (DSF) in combination with ifosfamide (IFX). DSF prevented IFX-induced bladder damage in a dose-dependent manner in tumour-free ddY mice when orally administered simultaneously with antitumour agent, but failed to diminish the acute lethal toxicity or leukocytotoxicity of IFX.