Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat.
BACKGROUND
We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats.


METHODS
TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry.


RESULTS
When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC.


CONCLUSIONS
Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.
Miampamba
M
M
Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
Parr
E J
EJ
McCafferty
D M
DM
Wallace
J L
JL
Sharkey
K A
KA
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008297:Male; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds; D015704:CD4 Antigens; D016827:CD8 Antigens; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase