title: Comprehensive cytotoxic evaluation of morin, a bioflavonoid against verapamil on rat gastrointestinal epithelium for novel pharmaceutical application involving P-glycoprotein inhibition.
abstract: OBJECTIVE
  In this study, a comprehensive and comparative cytotoxic evaluation of morin against verapamil on rat intestinal epithelium as P-gp inhibitors through in-vitro gastrointestinal short-term toxicity assays involving permeability studies for safety evaluation was investigated.
  
  
  METHODS
  In this study, the effect of morin (1 mM or 10 mM) or verapamil (1 mM or 10 mM) or sodium deoxycholate (10 mM) was investigated on intestinal epithelium and isolated brush border membrane using biomarker assays. Cytotoxicity was determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The nutrients transport was assessed using everted sacs studies. Paracellular permeability was measured using Lucifer yellow, followed by morphometric analysis of intestinal sacs.
  
  
  RESULTS
  Our results indicated that morin was effective in maintaining cell viability with no significant changes (P > 0.05) in the activity of intestinal brush border markers, membrane integrity and morphometric analysis as compared with control. On the contrary, dramatic (P < 0.01) changes were noticed in the release of membrane markers, cell viability and surface characteristics of intestinal segments when treated with verapamil or sodium deoxycholate as compared with control or morin.
  
  
  CONCLUSIONS
  Our findings confirm that morin is non-toxic to rat intestinal epithelium against verapamil demonstrating the potential use of bioflavonoid as safe and novel pharmaceutical adjuvant as P-gp inhibitor.
authors: Department of Pharmacology, Vaagdevi Institute of Pharmaceutical Sciences, Warangal, Telangana.
authors: Gurunath
authors: G
authors: Surampalli
authors: Department of Pharmaceutics, Omer Al-Mukhtar University, Tobruk, Libya.
authors: Basavaraj K
authors: BK
authors: Nanjwade
authors: Department of Pharmacology, International Medical Programme, USM-KLE University, Belgaum, Karnataka, India.
authors: Paragouda A
authors: PA
authors: Patil
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D002470:Cell Survival; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*; D047309:Flavones
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003840:Deoxycholic Acid; D005419:Flavonoids; D014700:Verapamil; C008548:morin; D047309:Flavones
keywords: P-gp inhibition; bioflavonoid; cytotoxic; morin; verapamil