Effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in broiler chickens

• Published in: Research in veterinary science Vol. 126; pp. 178 - 183
• Main Authors: Patel, Harshad B., Patel, Urvesh D., Mathapati, Basavaraj S., Modi, Chirag M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2019; Elsevier Limited
• Subjects: Alkaloids - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Antimicrobial agents; Antioxidants - pharmacology; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Avian Proteins - genetics; Avian Proteins - metabolism; Benzodioxoles - pharmacology; Bioavailability; Broiler chickens; Chickens; Chickens - genetics; Chickens - physiology; Combined treatment; Committees; CYP2D6 protein; Cytochrome; Cytochrome P-450 Enzyme Inhibitors - pharmacology; Cytochrome P450; Cytochrome P450 Family 3 - genetics; Cytochrome P450 Family 3 - metabolism; Drug dosages; Drug metabolizing enzyme; Drug resistance; Drugs; Duodenum; Duodenum - drug effects; Duodenum - metabolism; Efflux; Fluoroquinolones - pharmacology; Gene expression; Gene Expression Regulation - drug effects; Intestine; Liver; Liver - drug effects; Liver - metabolism; Marbofloxacin; MDR1 protein; Metabolism; Multi drug resistance-1 gene; Oral administration; Organic chemistry; P-Glycoprotein; Pharmacokinetics; Piperidines - pharmacology; Piperine; Polyunsaturated Alkamides - pharmacology; Poultry; Pretreatment; Quercetin; Quercetin - pharmacology; Random Allocation; RNA, Messenger - genetics; RNA, Messenger - metabolism; Substrates; Veterinary medicine; United States > US; India; Broiler chickens; Piperine; Drug metabolizing enzyme; Marbofloxacin; Multi drug resistance-1 gene; Quercetin
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2019.09.005

After oral route of administration, drug absorption is unpredictable and is governed by various factors such as multi drug resistance-1 (MDR1) an efflux transporter and drug metabolizing enzymes (like CYP3A4, CYP3A37, CYP2D6) at intestine and liver. Naturally available phyto chemicals like piperine and quercetin as well as some floroquinolones are known to inhibit MDR1 and CYP3A37 activity and increases bioavailability of co-administered drugs. This study was carried out to investigate the effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in liver and intestine of broiler chicken. After oral administration of piperine and quercetin for 3 consecutive days followed by with or without oral administration of marbofloxacin for 5 days, CYP3A37 and MDR1 mRNA expression levels were determined using quantitative real-time PCR. Total of 36 broiler chickens in seven individual groups were treated with different regimen and the mRNA expression levels at duodenum and liver were analyzed with apt statistical tools. After piperine and quercetin combined treatment with marbofloxacin, CYP3A37 mRNA expression levels were significantly down regulated by 20.57 (p = .034) and 25.95 (p = .003) folds; and MDR1 mRNA expression levels were also significantly down regulated by 11.33 (p = .012) and 33.59 (p = .006) folds in liver and duodenum, respectively. Down regulation of CYP3A37 and MDR1 mRNA in liver and duodenum indicate the combined pretreatment of piperine and quercetin may be useful for improving the pharmacokinetics of orally administered drugs which are substrates for CYP3A37 and MDR1. •Piperine, quercetin with marbofloxacin shown higher down regulation of MDR-1 and CYP3A37 in duodenum compared to liver•Piperine and quercetin in combination shown significant down regulation of MDR-1 in duodenum only, not in liver•Marbofloxacin shown synergistic inhibitory effect on MDR-1 and CYP3A37 expressions in broiler chickens•Herb- drug interactions should be further explored for enhancing therapeutic effect of drugs