Effects of Anethole on Renal Function of Swiss Mice

<b>Background/Objectives:</b> Anethole, a terpenoid with several pharmacologic effects, is the major constituent of the essential oil of <i>Croton zehntneri</i> (EOCz), Pax & K. Hoffm, Euphorbiaceae. Due to the mild renal toxicity associated with high doses of EOCz, its potential therapeutic effects on several diseases, and the fact that its chemical composition consists of 80% anethole, the renal effects of anethole in mice were investigated. <b>Methods:</b> Mice were randomly divided into eight groups, dosed daily as follows: Group 1-CTRL (control; vehicle only); Groups 2-A100, 3-A125_2x, and 4-A250 (dosed with 100, 125 twice daily, and 250 mg/kg, <i>per os</i> anethole); Group 5-_SUBAKI (i.p. albumin to induce hyperproteinemia and proteinuria; subclinical acute kidney injury); and Groups 6-_SUBAKI+A100, 7-_SUBAKI+A125_2x, and 8-_SUBAKI+A250 (<i>per os</i> anethole + i.p. albumin). <b>Results:</b> The A125_2x and A250 groups significantly increased urinary proteinuria and interstitial inflammation (<i>p</i> < 0.001, for these groups). _SUBAKI+A100, _SUBAKI+A125_2x, and _SUBAKI+A250 showed a neither protective nor additive effect in the proteinuria induced by anethole and by administered albumin. The anethole-induced proteinuria was spontaneously reversible in approximately 4 weeks. In vitro experiments showed that anethole (300 µg/mL) inhibits albumin uptake from the culture medium by tubular cells. <b>Conclusions:</b> Anethole at high doses bears renal acute toxicity that, although mild and spontaneously fully reversible, must be taken into consideration in a cost-benefit analysis.