Drug-induced phospholipidosis: issues and future directions
Mark J Reasor1, Kenneth L Hastings, Roger G Ulrich
1Robert C Byrd Health Sciences Center of West Virginia University, Department of Physiology and Pharmacology, P.O. Box 9229, Morgantown, WV 26506, USA. mreasor@hsc.wvu.edu
Expert Opinion on Drug Safety
|June 16, 2006
Summary
Cationic amphiphilic drugs can cause phospholipidosis, a reversible condition of phospholipid accumulation in cells. Further research is needed to understand its functional consequences and develop biomarkers for assessment.
Area of Science:
- Pharmacology
- Cell Biology
- Toxicology
Background:
- Cationic amphiphilic drugs induce phospholipidosis, characterized by reversible phospholipid accumulation and lamellar body formation in cells.
- The mechanisms underlying drug-induced phospholipidosis are complex and can vary between different compounds.
Purpose of the Study:
- To review the current understanding of drug-induced phospholipidosis.
- To highlight the need for further research into the functional consequences of this condition.
- To emphasize the necessity for developing biomarkers for phospholipidosis assessment.
Main Methods:
- Literature review of studies on cationic amphiphilic drugs and phospholipidosis.
- Analysis of data on the characteristics, mechanisms, and consequences of phospholipidosis.
- Evaluation of existing screening procedures and the need for new biomarkers.
Main Results:
- Phospholipidosis is a common cellular response to various drugs.
- The functional impact of phospholipidosis on cellular and tissue function remains poorly understood.
- Current screening methods exist, but validated biomarkers for preclinical and clinical assessment are lacking.
Conclusions:
- Phospholipidosis is a complex drug-induced cellular response requiring further investigation.
- Clarifying whether phospholipidosis is adaptive or toxic is crucial for regulatory assessment.
- Development of reliable biomarkers is essential for monitoring phospholipidosis in research and clinical settings.
Related Concept Videos
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:27Synthesis of Phosphatidylcholine in the ER Membrane
The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
The major components of all eukaryotic cell...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Understanding serum lipids is crucial for maintaining cardiovascular health and preventing heart disease and stroke.
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:28Overview of Fatty Acid Metabolism
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...