Purified fumonisin B(1) decreases cardiovascular function but does not alter pulmonary capillary permeability in swine.

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Res. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B(1) was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B(1) at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B(1)-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B(1), and that fumonisin-induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration.

The early effects of dietary restriction on the pathogenesis of chronic renal disease in Sprague-Dawley rats at 12 months.

This study evaluated the effects of different diets and dietary regimens on the pathogenesis of chronic renal disease (CRD) in Sprague-Dawley rats at 52 wk and correlated these data with survival at 106 wk. A commercial diet (5002) was compared to a modified diet (5002-9) with less protein, fat, and energy and more fiber. Both diets were fed by ad libitum (AL) or dietary restriction (DR) regimens. The glomerular area (GA), glomerular sclerotic index (GSI), tubulo-interstitial index (TII), and tubular labeling index (tubular LI) were measured. The 5002-9 diet fed AL did not decrease the severity of CRD or increase survival, nor did the 5002 diet fed 6.5 hr/day. Both diets fed by DR did improve CRD and survival. Both AL groups had higher indices, and the 5002 AL males had the highest GA and GSI. These data indicate that the initial events in CRD occur as glomerular hypertrophy. Because the TII and tubular LI were only increased with advanced CRD, tubulo-interstitial damage did not occur until the glomerular changes were established. The 52-wk glomerular indices correlated with survival at 106 wk. Increased GA at 52 wk predicted low survival rates at 106 wk. These findings support a hypothesis that glomerular sclerosis and tubulo-interstitial damage occur secondary to early initial glomerular hypertrophy that is mitigated by caloric restriction.