Tubular segment-specific biomarkers of nephrotoxicity in the rat. 2001

A Trevisan, and M Giraldo, and M Borella, and S Bottegal, and A Fabrello
Laboratory of Industrial Toxicology, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy. atrevi@ux1.unipd.it

Segment-specific localization of p-aminohippuric acid accumulation and glutamine synthetase activity along the proximal tubule was investigated in kidneys of rats treated with segment-specific nephrotoxicants such as potassium dichromate (pars convoluta) and hexachloro-1:3-butadiene (pars recta). Potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene caused a significant, dose-dependent decrease of p-aminohippuric acid uptake in the renal cortical slices 24 and 48 h after the treatment. In contrast, hexachloro-1:3-butadiene and only the highest dose (40 mg/kg b.w.) of potassium dichromate, caused a significant dose-dependent decrease of glutamine synthetase activity in the kidney beginning 24 h after treatment. Finally, potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene (48 h after the treatment) caused a significant dose-dependent loss of kidney protein content. The results suggest that p-aminohippuric acid accumulation is localized in the pars convoluta and confirm that glutamine synthetase is in the pars recta of the rat proximal tubule. p-Aminohippuric acid uptake impairment and glutamine synthetase activity loss caused by the highest doses of hexachloro-1:3-butadiene and potassium dichromate, respectively, suggests that high doses of segment-specific chemicals may involve other portions of the proximal tubule; in addition, the decrease of glutamine synthetase activity caused by potassium dichromate may be related to the protein content loss.

UI MeSH Term Description Entries
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008297 Male Males
D010130 p-Aminohippuric Acid The glycine amide of 4-aminobenzoic acid. Its sodium salt is used as a diagnostic aid to measure effective renal plasma flow (ERPF) and excretory capacity. 4-Aminohippuric Acid,para-Aminohippuric Acid,Aminohippurate Sodium,Aminohippuric Acid,Nephrotest,Sodium Para-Aminohippurate,p-Aminohippurate,4 Aminohippuric Acid,Para-Aminohippurate, Sodium,Sodium Para Aminohippurate,Sodium, Aminohippurate,p Aminohippurate,p Aminohippuric Acid,para Aminohippuric Acid
D011192 Potassium Dichromate Chromic acid (H2Cr2O7), dipotassium salt. A compound having bright orange-red crystals and used in dyeing, staining, tanning leather, as bleach, oxidizer, depolarizer for dry cells, etc. Medically it has been used externally as an astringent, antiseptic, and caustic. When taken internally, it is a corrosive poison. Potassium Bichromate,K2Cr2O7,Bichromate, Potassium,Dichromate, Potassium
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D002424 Caustics Strong alkaline chemicals that destroy soft body tissues resulting in a deep, penetrating type of burn, in contrast to corrosives, that result in a more superficial type of damage via chemical means or inflammation. Caustics are usually hydroxides of light metals. SODIUM HYDROXIDE and potassium hydroxide are the most widely used caustic agents in industry. Medically, they have been used externally to remove diseased or dead tissues and destroy warts and small tumors. The accidental ingestion of products (household and industrial) containing caustic ingredients results in thousands of injuries per year. Caustic,Corrosive,Corrosives
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005659 Fungicides, Industrial Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. Industrial Fungicides
D005974 Glutamate-Ammonia Ligase An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2. Glutamine Synthetase,Glutamate Ammonia Ligase (ADP),Glutamate Ammonia Ligase,Ligase, Glutamate-Ammonia,Synthetase, Glutamine
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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