Hydrophilic interaction chromatography with a focus on the drug-phosphate interaction in drug screening to determine the phospholipidosis induction risk.

Cationic amphiphilic drugs (CADs) can induce the hyperaccumulation of phospholipids in cells and tissues. This side effect, which is known as drug-induced phospholipidosis, is sometimes problematic in the development and clinical use of CADs. It is known that CADs generally interact with phospholipids via both hydrophobic and acid-base interactions, and CADs with the larger affinity to phospholipid exhibit the larger induction risk.

Putative biomarker for phospholipid accumulation in cultured cells treated with phospholipidosis-inducing drugs: alteration of the phosphatidylinositol composition detected using high-performance liquid chromatography-tandem mass spectrometry.

We developed a high-performance liquid chromatography-tandem mass spectrometric method for phospholipid biomarker discovery and applied it to a cell-based assay system for the screening of phospholipidosis-inducing drugs. We studied the compositions of phospholipid molecules exceeding 100 species in cultured cells and found a characteristic alteration in the composition by treatment with cationic amphiphilic drugs possessing phospholipidosis-inducing potency. The compositions of phosphatidylinositol in RAW264 cells were significantly affected by the drug treatment.

Maintenance of luminal pH and protease activity in lysosomes/late endosomes by vacuolar ATPase in chlorpromazine-treated RAW264 cells accumulating phospholipids.

Cationic amphiphilic drugs (CADs) inhibit phospholipases competitively/uncompetitively. It has also been reported that CADs spontaneously accumulate in acidic organelles and increase their luminal pH, which may lead to deactivation of phospholipid-metabolising enzymes, causing cellular phospholipid accumulation. Recently, however, contradictory results have also been reported in that the luminal pH is not increased by CAD treatment.

Factors affecting the sensitivity of human-derived esophageal carcinoma cell lines to 5-fluorouracil and cisplatin.

Effective chemotherapy against esophageal carcinoma is considered achievable with a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). However, chemo-therapy remains ineffective in certain patients. The aim of this study was to clarify the factors which affect sensitivity to 5-FU and CDDP.

Improved capillary electrophoresis method for the analysis of carbohydrate-deficient transferrin in human serum, avoiding interference by complement C3.

Capillary electrophoresis (CE) methods for transferrin analysis are widely used in clinical laboratories, but complement C3 peaks often overlap with carbohydrate-deficient transferrin peaks. In this study, we discovered that the electrophoretic mobility of the complement C3 peak could be controlled by adding carboxymethylcellulose (CMC) and dextran sulfate (DS) to the background electrolyte solution, probably because of adsorption of the polyanions to the proteins. The improved capillary electrophoresis method was developed using spermine, CMC, and DS as the background electrolyte solution additives.

Role of bis(monoacylglycero)phosphate in propranolol binding to phospholipid membranes under acidic conditions as measured by high-performance frontal analysis/capillary electrophoresis.

Bis(monoacylglycero)phosphate (BMP) is localized in acidic organelles such as late endosomes or lysosomes. It has been reported that BMP levels increase under phospholipidosis induced by cationic amphiphilic drugs. In the present study, the effect of BMP on the binding of propranolol (PRO) to phospholipid liposomes under acidic conditions was investigated.