Impact of Pineapple on Mitochondrial Permeability Transition and Drug Metabolizing Genes in Caco-2 Cells.
Pak J Biol Sci
; 24(12): 1217-1225, 2021 Jan.
Article
in En
| MEDLINE
| ID: mdl-34989199
ABSTRACT
<b>Background and Objective:
</b> Pineapple (<i>Ananas comosus</i> L.) has antioxidant and other pharmacological properties. This study examined how pineapple modified mitochondrial permeability transition and expression of drug-metabolizing enzymes, i.e., CYP1A2, CYP2C9, CYP3A4, UGT1A6, NAT2 and the drug transporter OATP1B1 in human colorectal adenocarcinoma (Caco-2) cells. <b>Materials andMethods:
</b> Caco-2 cells (2.5×10<sup>5</sup> cells well<sup>1</sup> in 24-well plates) were incubated with pineapple (125 to 1,000 µg mL<sup>1</sup>) for 48 hrs in a phenol red-free medium. Mitochondrial permeability transition, resazurin cell viability and AST and ALT levels were investigated. The mRNA expression of target genes was determined by RT/qPCR. <b>Results:
</b> Pineapple significantly reduced depolarized mitochondria, slightly decreased cell viability and did not change AST and ALT levels. Pineapple did not modify the mRNA expressions of CYP1A2, CYP2C9 and CYP3A4 but markedly induced UGT1A6 expression. The highest tested concentration of pineapple (1,000 µg mL<sup>1</sup>) significantly suppressed NAT2 and OATP1B1 expression. <b>Conclusion:
</b> Although pineapple slightly decreased cell viability to ~80% of control, the morphology and functions of the cells were unaffected. Pineapple showed a beneficial effect to reduce depolarized mitochondria, which consequently decreased reactive oxygen species production. Pineapple did not modify the expression of CYPs, whilst it altered the expression of phase 2 metabolizing genes UGT1A6 and NAT2 and the transporter OATP1B1. Therefore, the consumption of large amounts of pineapple is of concern for the risk of drug interaction via alteration of UGT1A6, NAT2 and OATP1B1 expression.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Caco-2 Cells
/
Ananas
/
Mitochondrial Transmembrane Permeability-Driven Necrosis
Limits:
Humans
Language:
En
Journal:
Pak J Biol Sci
Year:
2021
Document type:
Article
Publication country:
PAKISTAN
/
PAQUISTÃO
/
PK