Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats

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Abstract

Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and result in changes in drug disposition.

Aim

This study was aimed to examine the development-, aging-, and sex-dependent changes in Mrp1–4 and ATP-binding cassette sub-family G member 2 (Abcg2) gene expressions in livers of rats.

Main methods

The livers from male and female SD rats at development (−2, 1,7,14,21,28,35, and 60 d) and aging (28, 60, 180 and 540 d) were collected and total RNA was isolated, purified and subjected to real-time RT-PCR analysis.

Key findings

Results showed that expression of Mrp1 was low, while Abcg2 and Mrp2 were the high in the liver. Mrp1 expression decreased with maturity but remained constant to 540 d, while Mrp3 and 4 increased with liver development, reached the peak with maturity at 35–60 days of age, and slightly reduced with aging. Mrp2 and Abcg2 were high at 7 days of age and maintained at relative high levels till maturity, while Abcg2 was reduced during aging. Females had higher Mrp3 and Abcg2 mRNA expression than male rats, while male rats had higher Mrp2 and Mrp4 mRNA expression.

Significance

The expression of hepatic Mrp1–4 and Abcg2 mRNA during development, aging in male and female rats was characterized, which could be fundamental to our understanding of age- and sex-associated variations in drug disposition in children, elderly, and women.

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