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Decreased Lithium Disposition to Cerebrospinal Fluid in Rats with Glycerol-induced Acute Renal Failure

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Abstract

Purpose

The lithium disposition to cerebrospinal fluid (CSF) was evaluated in rats with acute renal failure (ARF) to examine whether electrolyte homeostasis of the CSF is perturbed by kidney dysfunction. In addition, the effects of renal failure on choroid plexial expressions of the Na+–K+–2Cl− co-transporter (NKCC1) and Na+/H+ exchanger (NHE1) were also studied.

Methods

After lithium was intravenously administered at a dose of 4 mmol/kg, its concentration profile in plasma was evaluated by collecting plasma specimens, while that in CSF was monitored with a microdialysis probe in the lateral ventricles. NKCC1 and NHE1 expressions were measured via the Western immunoblot method using membrane specimens prepared from the choroid plexus in normal and ARF rats.

Results

The lithium concentration in CSF of ARF rats was 30% lower than that of normal rats, while their plasma lithium profiles were almost the same, indicating that the lithium disposition to CSF was decreased in ARF rats. It was revealed that the choroid plexial expression of NKCC1 was increased by 40% in ARF rats, but that of NHE1 was unchanged.

Conclusion

ARF decreases the lithium disposition to CSF, possibly by promoting lithium efflux from CSF due to increased NKCC1 expression in the choroid plexus.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Sciences.

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Authors and Affiliations

  1. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Okayama, 700-8530, Japan

    Rie Sakae, Atsuko Ishikawa, Tomoko Niso, Yukiko Komori, Tetsuya Aiba, Hiromu Kawasaki & Yuji Kurosaki

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  1. Rie Sakae
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  2. Atsuko Ishikawa
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Correspondence to Tetsuya Aiba.

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Sakae, R., Ishikawa, A., Niso, T. et al. Decreased Lithium Disposition to Cerebrospinal Fluid in Rats with Glycerol-induced Acute Renal Failure. Pharm Res 25, 2243–2249 (2008). https://doi.org/10.1007/s11095-008-9612-5

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