Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1 induction but not inflammatory responses in rat liver
Section snippets
Chronic administration of ethanol
Thirty-one specific pathogen-free male Wistar rats in littermate pairs, weighing 144–188 g, were housed in stainless steel wire-bottom cages and divided in four groups. Two groups received control diet and two ethanol diet. To cause inactivation of Kupffer cells, GdCl3 (Sigma Chemical Co., St. Louis, MO, USA) was injected (10 mg/kg in acidic saline) into the tail vein every third day to one control group and one ethanol group. Controls received acidic saline. The rats were fed for 6 weeks a
Results
All groups of rats gained weight throughout the 6-week period. Although the weight gain of control rats was somewhat higher (170 g±8), it was not significantly different from that of rats treated with ethanol (138 g±8) or with gadolinium only (148 g±4), but the combination of ethanol and gadolinium led to a somewhat reduced weight gain (110g±11, p<0.05). The mean daily ethanol consumption of rats on ethanol diet was 12.6±0.9 g/kg b.wt. and additional gadolinium treatment had no influence
Discussion
This study demonstrates that in the present model GdCl3 alleviates ALD mainly by reducing steatosis, and that there is a concurrent reduction of the ethanolinduced CYP2E1 induction. Treatment with GdCl3 did not significantly reduce inflammation. Thus our results do not support the suggestion that GdCl3 protects primarily via pro-inflammatory pathways, such as CD14-LBP regulated Kupffer cell activation15. The counteracting effect of GdCl3 on steatosis may nevertheless be a crucial protective
Acknowledgements
We are indebted to Dr Päivi Kärkkäinen, Department of Pathology, University Hospital of Helsinki, for valuable guidance in the histopathological evaluation and to Johanna Saarikko for technical assistance. The expert technical assistance of Gunilla Rönnholm throughout this study has been invaluable. This study was supported by grants from the following sources: ACHRI grant 1 R21 AA12031-01 (to KL and MIS), the Oskar Öflund Foundation (to HJ), the Yrjö Jahnsson foundation (to TL) and The Swedish
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