title: Effect of two esters of N-methylanthranilic acid from Rutaceae species on impaired kidney morphology and function in rats caused by CCl4.
abstract: OBJECTIVE
  Herein we investigated the potential protective effects of methyl N-methylanthranilate (MA) and isopropyl N-methylanthranilate (IA), two naturally occurring plant constituents from Rutaceae taxa, in a rat model of acute intoxication with carbon tetrachloride (CCl4) by tracking changes in kidney tissue morphology and function.
  
  
  METHODS
  The antioxidant capacity of IA and MA was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid radical cation (ABTS(+)) assays and superoxide-scavenging test. Wistar rats were treated daily with MA and IA for seven days in a dose of 200mg/kg. Twenty-four hours after a CCl4 injection, rats were sacrificed and blood samples were used for the evaluation of urea and creatinine. Kidney tissue specimens were stained with hematoxylin and eosin, periodic acid-Schiff and Jones stain and evaluated for morphological changes. Quantification of structural changes determined by histological analysis of kidney tissue was assessed by a morphometric analysis of glomeruli using ImageJ software.
  
  
  RESULTS
  IA and MA applied in high doses on their own did not cause any significant damage to kidney tissue. A pretreatment with MA prior to the administration of CCl4 significantly prevented the increase of serum levels of decreased kidney function markers, while that of IA did not. Histopathological evaluation of the kidneys also revealed that MA reduced the incidence of kidney lesions.
  
  
  CONCLUSIONS
  Our experiments showed that methyl-, and not isopropyl-, N-methylanthranilate possesses a protective potential against CCl4-induced kidney damage in rats. The results are of interest due to the presence of natural or synthetic methyl N-methylanthranilate in the human diet and their potent analgesic properties.
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia. Electronic address: nikoradulovic@yahoo.com.
authors.forename: Niko S
authors.initials: NS
authors.lastname: Radulović
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Niš, Zorana Đinđića 81, 18000 Niš, Serbia.
authors.forename: Pavle J
authors.initials: PJ
authors.lastname: Randjelović
authors.affiliation: Faculty of Medicine, University of Niš, Zorana Đinđića 81, 18000 Niš, Serbia.
authors.forename: Nikola M
authors.initials: NM
authors.lastname: Stojanović
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Niš, Zorana Đinđića 81, 18000 Niš, Serbia.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Ilić
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Miltojević
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
authors.forename: Milan B
authors.initials: MB
authors.lastname: Stojković
authors.affiliation: Pediatric Clinic, Laboratory of Biochemistry, Clinical Center and Medical Faculty of Niš, University of Niš, 18000 Niš, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Ilić
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051381:Rats; D027821:Rutaceae / Q000737:chemistry*; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000975:Antioxidants; D015415:Biomarkers; D062367:ortho-Aminobenzoates; C098239:6-methylanthranilic acid
keywords: Carbon tetrachloride; Isopropyl N-methylanthranilate; Kidney; Methyl N-methylanthranilate; Rat