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Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36 * 13% in pretreated rats, causing higher bile flow (P = 0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group (P

A distillate, D431, originating from Venezuelan heavy crude oil and a severely hydro-treated base oil, BO100, derived from this distillate, were tested for DNA adduct formation capacities and overall impact on liver functions. D431 had earlier showed DNA adduct formation in vitro but not in vivo in the rat. In this study, isolated rat liver perfusions were performed to elucidate whether the lack of DNA adducts in vivo was because of lack of uptake or metabolism. The oils were extracted with dimethyl sulfoxide and the extracts added to the perfusion system. Bile production, lactate metabolism and perfusate flow through the organ, which are parameters that reveal the condition of the liver, were continuously monitored. Samples of liver were collected once every hour during perfusion for DNA adduct analysis with (32)P-HPLC. The results for the distillate D431 showed that the production of bile and metabolism of lactate decreased while DNA adduct formation increased with time. The DNA adduct pattern formed in the D431-treated livers was similar to that found earlier in in vitro studies performed on calf thymus DNA (CT-DNA). In the case of DNA adduct formation, virtually no difference with dose was seen, suggesting that perhaps a point of saturation of, for instance, enzymatic systems was reached. The results for base oil BO100 showed no significant difference regarding bile production, lactate metabolism and DNA adduct formation when compared with the control, indicating no toxic or genotoxic activity.

Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36+/-13% in pre-treated rats, causing higher bile flow (P = 0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group (P < 0.02 and P < 0.05). In conclusion, augmented bile salt-dependent bile flow is preserved in the liver after cold storage. Enteral donor pre-treatment with UDCA protects the liver against ischaemia-reperfusion injury.

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