d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

Journal Article · Thu Jun 15 00:00:00 EDT 1989 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(89)90007-0· OSTI ID:5764153

Lehman-McKeeman, L D; Rodriguez, P A; Takigiku, R; Caudill, D; Fey, M L

d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in female rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.

• Research Organization: Procter Gamble Co., Cincinnati, OH (USA)
• OSTI ID: 5764153
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 99:2
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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TERPENES
TOXICITY
AMINO ACID SEQUENCE
CARBON 14 COMPOUNDS
DIALYSIS
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
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MAMMALS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SEPARATION PROCESSES
SYNTHESIS
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