Add time:07/21/2019         Source:sciencedirect.com

Cytembena (cis-β-4-methoxybenzoyl-β-bromoacrylic acid, NSC-104, 801) has been tested for its anticancer activity. One complication to its use is the possibility of drug-induced nephrotoxicity. The present study was designed to characterize further the nature of the renal damage. Rats injected ip with cytembena (50 or 150 mg/kg) showed urinary protein and glucose excretion, increased urine volumes (by 50 to 150%), and decreased urine osmolalities (from approx 1500 mosm/liter to approx 500 mosm/liter). No changes in urinary pH were noted. The slice-to-medium ratios (concentration per gram of tissue per concentration per milliliter of bathing medium) for p-aminohippurate (PAH) (with and without lactate), tetraethylammonium chloride, and α-aminoisobutyric acid uptakes were depressed by pretreatment with 150 mg/kg of cytembena. In addition, tissue slice electrolyte and water distributions were disrupted. Similar effects were produced with cytembena added directly to fresh slices, with the effects on PAH transport being the most marked. Because the organic compounds studied are transported by proximal tubules, it must be concluded that cytembena does have a proximal tubular effect.

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