Long-term acetaminophen (paracetamol) treatment causes liver and kidney ultra-structural changes during rat pregnancy. 2004

J Andalaft Neto, and R M Oliveira-Filho, and M J Simões, and J M Soares, and L Kulay
UNISA (Santo Amaro University), Medical School, Department of Obstetrics; São Paulo (Brazil).

Acetaminophen (paracetamol) is an analgesic-antipyretic drug virtually devoid of typical anti-inflammatory activity and hence free of some of the side-effects of aspirin and related agents (e.g. gastric erosion and bleeding complications). The worldwide use of paracetamol as a household analgesic, including during pregnancy, prompted us to investigate its potentially deleterious effects in that setting. Pregnant rats were treated with paracetamol (150, 500 or 1,500 mg/kg, once a day by gavage) from the first day up to term pregnancy. In the group treated with the lowest doses, no histological changes were noticed in maternal and fetal livers or kidneys when examined under light or electron microscopy. With the higher doses, however, various dose-dependent effects of paracetamol were observed, namely necrotic areas of the liver seen with light microscope and further confirmed by electron microscopy. The kidneys revealed degeneration and necrotic foci under light microscopy with ultrastructural derangements. Electronmicrographs of the liver revealed hepatocytes bearing translucent bodies as a consequence of a dilated smooth endoplasmic reticulum. There were signs of necrosis both in the hepatocytes (lysis of mitochondria and presence of lipid droplets) and renal tissue (mitochondrial cytolysis in convoluted tubules). Our data point out the fact that both maternal and fetal tissues can be adversely affected by paracetamol.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008853 Microscopy The use of instrumentation and techniques for visualizing material and details that cannot be seen by the unaided eye. It is usually done by enlarging images, transmitted by light or electron beams, with optical or magnetic lenses that magnify the entire image field. With scanning microscopy, images are generated by collecting output from the specimen in a point-by-point fashion, on a magnified scale, as it is scanned by a narrow beam of light or electrons, a laser, a conductive probe, or a topographical probe. Compound Microscopy,Hand-Held Microscopy,Light Microscopy,Optical Microscopy,Simple Microscopy,Hand Held Microscopy,Microscopy, Compound,Microscopy, Hand-Held,Microscopy, Light,Microscopy, Optical,Microscopy, Simple
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004721 Endoplasmic Reticulum A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed) Ergastoplasm,Reticulum, Endoplasmic
D005260 Female Females
D000082 Acetaminophen Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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