Development of multi-drug resistance to anticancer drugs in HepG2 cells due to MRP2 upregulation on exposure to menthol.

Background: Menthol exerts relaxing, antibacterial, and anti-inflammatory activities, and is marketed as a functional food and therapeutic drug.

Aim: In the present study, the effects of menthol on the expression of multidrug resistance associated protein 2 (MRP2) and its association with the cytotoxicity of epirubicin (EPI) and cisplatin (CIS) were examined using HepG2 cells.

Methods: The expression levels of target genes were examined by real-time PCR.

Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats.

Danazol (DNZ) is a synthetic androgen derivative used for the treatment of intractable hematological disorders. In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats.MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 h after DNZ (100 mg/kg, i.

Altered Gene Expression of Cytochrome P450 and ABC Transporter in Human Hepatocellular Carcinoma HepG2 Cells Exposed to Bardoxolone Methyl.

Bardoxolone methyl (BX) is expected to be an innovate therapeutic agent for chronic kidney disease (CKD). The aim of the present study was to examine whether the expression of subtypes of cytochrome P450 (CYP) and ABC transporters was altered in human hepatocellular carcinoma HepG2 cells by exposure to BX. The expression of mRNAs for CYP1A2, CYP2E1, P-glycoprotein, multidrug resistance-associated protein 1-3, and breast cancer resistance protein was significantly increased by exposure of HepG2 cells to BX, while the expression of CYP3A4 mRNA was significantly decreased under the same conditions.

Impact of Different Attitudes toward Face-to-Face and Online Classes on Learning Outcomes in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, online-based learning has become mainstream in many countries, and its learning outcomes have been evaluated. However, various studies have shown that online-based learning needs to be optimized in the future, and the number of reports for this purpose is currently not sufficient. The purpose in this study was to determine the relationship between academic performance and attitudes toward face-to-face and remote formats among Japanese pharmacy students enrolled in a course designed for knowledge acquisition.

Doxorubicin alters the disposition of phenytoin by reducing its metabolic elimination and binding affinity to serum albumin in rats.

Objectives: We investigated the pharmacokinetic interaction of doxorubicin (DOX) with phenytoin (PHT) and the underlying mechanism in rats to clarify why the serum PHT concentration decreases despite the impaired PHT metabolic capacity in patients receiving DOX.

Methods: Rats were administered 15 mg/kg of DOX or saline alone. The pharmacokinetic disposition of intravenously administered PHT was examined 4 days after DOX exposure.

Differences in Transport Characteristics and Cytotoxicity of Epirubicin and Doxorubicin in HepG2 and A549 Cells.

Background/aim: Epirubicin (EPI), an epimer of doxorubicin (DOX), and DOX are anthracycline agents with broad-spectrum antitumor activity. The aim of the present study was to elucidate the transport characteristics of EPI and DOX in human hepatocellular carcinoma HepG2 cells and human non-small cell lung cancer A549 cells, and to examine the relationship of intracellular drug accumulation with their cytotoxic effects.

Materials And Methods: Intracellular concentrations of EPI and DOX were measured using high-performance liquid chromatography (HPLC).

Effects of semi-solidification of enteral nutrients on the pharmacokinetic behavior of orally administered carbamazepine in rats.

The use of semi-solid enteral nutrients plays an extremely important role in accurate nutrition management. In the present study, we compared the pharmacokinetic profile of orally administered carbamazepine (CBZ) in rats treated with liquid RACOL, semi-solid RACOL, and HINE E-gel, which are enteral nutrients marketed in Japan. Since liquid and semi-solid formulations are both marketed in Japan for RACOL, liquid RACOL was orally administered to control rats.

Pharmacokinetic interference of doxorubicin with tolbutamide due to reduced metabolic clearance with increased serum unbound fraction in rats.

The study examined the effect of doxorubicin (DOX) on the hepatic expression of CYP2C and its activity for metabolizing tolbutamide (TB), a specific CYP2C substrate, in rats and whether the pharmacokinetics of tolbutamide were altered by doxorubicin exposure. The expression level of hepatic CYP2C11 was depressed 1 day after doxorubicin administration (day 1), and this effect on CYP2C11 was augmented on day 4. However, the expression level of hepatic CYP2C6 remained unchanged.

Conflicting alterations in hepatic expression of CYP3A and enzyme kinetics in rats exposed to 5-fluorouracil: relevance to pharmacokinetics of midazolam.

1. 5-Fluorouracil (5-FU) is a pyrimidine derivative widely used for the treatment of cancer. In this study, we investigated the effects of 5-FU on the protein expression of hepatic CYP3A and their enzyme activity for metabolizing midazolam (MDZ), a typical substrate of CYP3A, in rat liver microsomes.

Compatibility of Intravenous Fat Emulsion with Antibiotics for Secondary Piggyback Infusion.

Background: The Guidelines for Parenteral and Enteral Nutrition in Japan state that parenteral fat emulsion can be infused through a secondary administration set. We tested the compatibility of fat emulsion with antibiotics in piggyback infusions in terms of changes in the size distribution of fat particles.

Methods: Test mixtures of 5% glucose solution, fat emulsion, and 25 antibiotic agents were prepared in the ratio appropriate for piggyback infusion (33: 10: 40) and analyzed serially for the number of fine particles by size using a light-shielded automatic fine particle counter.

Alterations in Pharmacokinetics of Orally Administered Carbamazepine in Rats Treated with Sodium alginate: Possible Interaction between Therapeutic Drugs and Semi-solid Enteral Nutrients.

Objective: The use of enteral nutrients plays an extremely important role in accurate nutrition management. Sodium alginate (SA) is frequently used for the semi-solidification of enteral nutrients. In the present study, we investigated whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is altered by a treatment with SA immediately before and after dosing of the drug.

Pharmacokinetics and metabolic elimination of tolbutamide in female rats: Comparison with male rats.

As there are to be known gender differences in the expression profiles of rat hepatic CYP2C, we examined the pharmacokinetic behavior of tolbutamide (TB), a typical probe for CYP2C, and hepatic enzyme activities for metabolizing TB in female rats to compare with male rats. On the pharmacokinetic analysis of TB after intravenous administration to female rats, the elimination rate constant at the terminal phase (k ), total clearance (CL ) and the apparent volume of distribution at steady-state (Vd ) were significantly lower than in male rats. The binding rates of TB to serum protein were similar in male and female rats, indicating that the change in unbound TB concentration in serum is not associated with the difference in the pharmacokinetic disposition of TB.

Prevention of Doxorubicin-Induced Renal Toxicity by Theanine in Rats.

Doxorubicin (DOX) is a highly potent anti-neoplastic agent widely used in clinical practice, but its dosage and duration of administration are strictly limited due to dose-related organ damage. In the present study, we examined whether theanine, an amino acid derivative found in green tea leaves, can protect against DOX-induced acute nephrotoxicity in rats. Decreases in the creatinine clearance by DOX administration were attenuated by concurrent treatment with theanine, which was consistent with the change in histological renal images assessed by microscopic examination.

Bactericidal effects of deep ultraviolet light-emitting diode for solutions during intravenous infusion.

Ultraviolet irradiation is effectively used as a disinfection method for inactivating microorganisms. We investigated the bactericidal effects by irradiation with a deep-ultraviolet light-emitting diode (DUV-LED) on the causative microorganisms of catheter related blood stream infection contaminating the solution for intravenous infusion. For irradiation, prototype modules for water disinfection with a DUV-LED were used.

In vitro and in vivo effects of selected fibers on the pharmacokinetics of orally administered carbamazepine: Possible interaction between therapeutic drugs and semisolid enteral nutrients.

Objective: The management of nutrition using semisolid enteral nutrients is considered useful for avoiding the adverse effects associated with liquid enteral nutrients. In the present study, we used an in vitro analysis to investigate whether carbamazepine (CBZ) is adsorbed by the fibers included in semisolid enteral nutrients. The effects of these fibers on the pharmacokinetic profile of CBZ following its oral administration were also examined in rats.

Water Soluble Vitamins Enhance the Growth of Microorganisms in Peripheral Parenteral Nutrition Solutions.

Peripheral parenteral nutrition (PPN) solutions contain amino acids, glucose, and electrolytes, with or without some water soluble vitamins. Peripheral venous catheters are one of the causes of catheter related blood stream infection (CRBSI), which requires infection control. In Japan, PPN solutions have rarely been prepared under aseptic conditions.

Altered tolbutamide pharmacokinetics by a decrease in hepatic expression of CYP2C6/11 in rats pretreated with 5-fluorouracil.

1. We investigated the change in the pharmacokinetic profile of tolbutamide (TB), a substrate for CYP2C6/11, 4 days after single administration of 5-fluorouracil (5-FU), and the hepatic gene expression and activity of CYP2C6/11 were also examined in 5-FU-pretreated rats. 2.

Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses.

The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment.

Decreased elimination clearance of midazolam by doxorubicin through reductions in the metabolic activity of hepatic CYP3A in rats.

1. We examined the effects of doxorubicin (DOX) on the expression level and metabolic activity of CYP3A in the liver as well as on the pharmacokinetics of midazolam (MDZ), a probe for CYP3A, in rats. Changes in the hepatic status of DOX-treated rats were confirmed.

Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response.

Doxorubicin (DOX) is widely used as an antitumor agent with topoisomerase II inhibiting activity; however, its dosage and duration of administration have been strictly limited due to dose-related organ damage. The present study investigated whether theanine, an amino acid found in green tea leaves, could reduce DOX-induced acute hepatotoxicity and the apoptotic response in mice. Activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, biomarkers of hepatic impairment, were markedly increased after the administration of 20 mg/kg DOX, whereas the degree of these elevations was significantly attenuated by 10 mg/kg theanine, which was consistent with histological hepatic images assessed by microscopic examination.

Change in pharmacokinetic behavior of intravenously administered midazolam due to increased CYP3A2 expression in rats treated with menthol.

Menthol is used widely as a constituent of functional foods and chemical drugs. The present study investigated changes in the pharmacokinetic behavior of intravenously administered midazolam (MDZ), a probe for CYP3A, when rats were treated with menthol. The study also examined which isoforms of CYP3A1 and 3A2 were menthol-inducible and contributed to the altered disposition of midazolam.

Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats.

We compared the degree of nephrotoxicity of vancomycin (VCM) administered once daily and twice daily in rats. VCM was intraperitoneally administered once daily to rats at a dose of 400 mg/kg (VCM-1-treated) or administered at a dose of 200 mg/kg twice daily at 12-hour intervals (VCM-2-treated) for 7 consecutive days. Creatinine clearance was decreased more markedly in VCM-1 rats relative to VCM-2 rats, although there was no significant difference in renal accumulation of VCM between the two groups.

Underestimation of rat serum vancomycin concentrations measured by an enzyme-multiplied immunoassay technique and the strategy for its avoidance.

An enzyme-multiplied immunoassay technique (EMIT) has been widely adopted for the measurement of serum concentrations of vancomycin (VCM) in clinical practice. Because of the growing demand for its application to fundamental pharmacokinetic studies, we examined whether VCM concentrations in rat serum were accurately measured by EMIT. It was found that measured values of known amounts of VCM spiked to rat serum were markedly underestimated with a large analytical variance.