Vascular and glomerular effects of Clostridium difficile toxin A peptide on the isolated rat kidney.
Toxin A peptide from Clostridium difficile caused damage and secretion in the intestinal mucosa. These effects are mediated in part by pro-inflammatory substances. In order to evaluate and compare the biologic effect of toxin A on renal vascular, glomerular and tubular functions, we studied this toxin in isolated rat kidneys. Isolated kidneys from adult male Wistar rats (260-320 g) were perfused with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin. We studied the effect of toxin A peptide (3.2 x 10(-6) M, injected into perfusate) on glomerular filtration rate (GFR), urinary flow rate (UF) and total sodium reabsorption (TNa+, %). All experiments were preceded by a 30-min basal period, and in another group of kidneys the time course of the variables was followed without toxin infusion for unpaired control. Toxin A (TxA) reduced the perfusion pressure (PP), from PPcontrol/30min = 124.89 +/- 1.91 to PPTxA/120min = 88.13 +/- 5.1 mmHg (N = 6, P < 0.01) with a maximal effect at 120 min after toxin infusion. TxA also caused a significant decrease in GFR with maximal effect at 90 min after toxin infusion (GFRcontrol/30min = 0.53 +/- 0.05 to GFRTxA/90min = 0.30 + 0.05 ml min-1g-1; N = 6, P < 0.01). TxA did not alter renal tubular sodium transport when compared with a control without toxin infusion. In addition, toxin-treated kidneys caused a time-dependent increase in urinary flow from UFcontrol/30min = 0.16 +/- 0.08 to UFTxA/120min = 0.35 +/- 0.1 ml min-1g-1 (N = 6, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Monteiro
H S
HS
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brasil.
Santos-Neto
M S
MS
Oliveira
A V
AV
Lima
A A
AA
Lyerly
D M
DM
Fonteles
M C
MC
D000818:Animals; D001427:Bacterial Toxins; D001693:Biological Transport, Active / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D012964:Sodium