Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice.
BACKGROUND
Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated.


METHODS
The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days.


RESULTS
The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice.


CONCLUSIONS
Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model.
Fukuoka
Naomi
N
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Okayama, Japan.
Sugiyama
Hitoshi
H
Inoue
Tatsuyuki
T
Kikumoto
Yoko
Y
Takiue
Kei-ichi
K
Morinaga
Hiroshi
H
Nakao
Kazushi
K
Maeshima
Yohei
Y
Asanuma
Masato
M
Wang
Da-Hong
DH
Ogino
Keiki
K
Masuoka
Noriyoshi
N
Makino
Hirofumi
H
D020642:Acatalasia / Q000150:complications*; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D002374:Catalase / Q000097:blood / Q000502:physiology; D002710:Chlorhexidine; D003849:Deoxyguanosine / Q000032:analysis; D005355:Fibrosis / Q000139:chemically induced / Q000209:etiology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016877:Oxidants / Q000633:toxicity*; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*
D016877:Oxidants; D002374:Catalase; D003849:Deoxyguanosine; D002710:Chlorhexidine