Urinary transforming growth factor-beta (TGF-beta) excretion and renal production of TGF-beta in rats with subtotal renal ablation: effect of enalapril and nifedipine.

The aim of the present study was to investigate the effect of enalapril and nifedipine on renal transforming growth factor-beta (TGF-beta) production and on the rate of urinary TGF-beta excretion in rats with subtotal renal ablation. After subtotal nephrectomy some animals were treated with enalapril or nifedipine. Renal cortical TGF-beta mRNA levels were 68% higher in untreated nephrectomized rats (p < 0.05) and 39% higher in rats treated with nifedipine (p < 0.05) compared with controls. There was no difference in renal cortical TGF-beta mRNA content between the nephrectomized rats treated with enalapril and sham animals, showing that enalapril treatment prevented the increase of TGF-beta mRNA in nephrectomized rats. The rate of urinary TGF-beta excretion was 2.2 +/- 0.8 pg/min in sham animals, 61.5 +/- 40.1 pg/min in untreated nephrectomized rats, 9.6 +/- 4.2 pg/min in nephrectomized rats treated with enalapril, and 55.2 +/- 24.46 pg/min in rats treated with nifedipine. The immunohistochemical reaction for TGF-beta in the renal cortex was less intense in the nephrectomized rats treated with enalapril than in the other groups of rats with subtotal renal ablation. These data show that enalapril induces a decrease in renal TGF-beta production and in urinary TGF-beta excretion in rats with subtotal renal ablation, an effect associated with the protective action of this treatment on renal structure and function and suggest that the determination of the rate of urinary TGF-beta could be a useful procedure for the evaluation of disease progression and therapeutic efficacy in the remnant kidney model.

Chemistry, biology, and toxicology of domoic acid and its isomers.

The causative agent of toxicity in cultured mussels from a localized area of eastern Prince Edward Island has been identified as domoic acid, a neuroexcitatory amino acid. The toxin was isolated by a number of different bioassay-directed separation techniques including high-performance liquid chromatography (HPLC), high-voltage paper electrophoresis (HVPE), and ion-exchange chromatography, and characterized by a number of spectroscopic techniques including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance. The isolation and purification methods are described in detail and some new analytical data for domoic acid are reported. A plankton bloom at the time of the outbreak gave positive mouse bioassays and consisted almost entirely of the pennate diatom, Nitzschia pungens f. multiseries. A positive correlation was found between the number of N. pungens cells and the concentration of domoic acid in the plankton. N. pungens f. multiseries isolated from Cardigan Bay produced domoic acid de novo during stationary phase culture at levels (1 to 10 pg/cell) comparable to values estimated for N. pungens in the plankton samples. We conclude that N. pungens was the major source of the domoic acid in toxic mussels in eastern Prince Edward Island. The recurrence, in November 1988, of a monospecific bloom of N. pungens and the presence of domoic acid in plankton and mussels reinforces this conclusion.

Zinc from oyster tissue as causative factor in mouse deaths in official bioassay for paralytic shellfish poison.

Toxicity (extreme weakness, body temperature drop, cyanosis, some slow deaths) in test mice, upon intraperitoneal injection of standard-method paralytic shellfish poison (PSP) extracts of some PSP-free oysters, is consistent with the relatively high levels of zinc in these extracts. As a rough guideline, the threshold for a toxic response corresponds to a drained tissue zinc level of over 900 micrograms/g. The identification of zinc as the substance responsible has been supported by inducing toxicity in control extracts by spiking with nontoxic levels of zinc, and by eliminating toxicity from toxic extracts by chemical removal (precipitation, ion exchange) of metals.