Concentration-dependence of dithiothreitol effects on rat distal colon electrophysiology.
Dithiothreitol (DTT), at 1 mmol/L or higher, is widely used as a mucolytic in gastrointestinal research. Previous observations suggest that it may be toxic to the mucosa. DTT effects on the mucosal electrical behavior were assessed. Cumulative concentration-response relationships of DTT effects on rat distal colon mucosa were studied. Isolated mucosa preparations were mounted in an Ussing chamber under short-circuit conditions. The effects of concentrations ranging from 1 mumol/L to 1 mmol/L, applied to either the mucosal or serosal side, were studied. As compared with control, untreated preparations, DTT depressed short-circuit current at 10 mumol/L and higher when applied to the serosal side, and at 50 mumol/L and higher when applied to the mucosal side of the epithelium. On the other hand, transepithelial resistivity showed a progressive increase with DTT applied to either side at a concentration of up to 500 mumol/L, while at the highest concentration (1 mmol/L) a marked decrease in resistivity occurred. Neither the short-circuit current decrease, nor the resistivity collapse showed recovery after repeated rinsing with DTT-free solution. It is concluded that DTT affects epithelial electrical properties at low concentrations, and therefore its use as a mucolytic for electrophysiological studies should be discouraged.
Saraví
F D
FD
Departamento de Morfofisiología (Area Biofísica), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla 33, (5500) Mendoza, Argentina. fsaravi@fmed2.uncu.edu.ar
Saldeña
T A
TA
Arrieta
O R
OR
Cincunegui
L M
LM
Carra
G E
GE
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004229:Dithiothreitol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005100:Expectorants / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005100:Expectorants; D005765:Gastrointestinal Agents; D004229:Dithiothreitol