Protective effects of antioxidants on hepatic ischemia damage after portacaval shunt in dogs

Abstract

AIM: To study the role of lipid peroxides reaction on hepatic ischemia damage and the protective effects of antioxidants (TMP, co-Q10).

METHODS: Twenty-four adult dogs were performed portacaval shunt and randomly put into 3 groups: group 1 (control group); 8 dogs with portacaval shunt (PCS group); group 2: 8 dogs with portacaval shunt and only given antioxidants TMP (ligustrazine) (PCS + TMP group); group 3: 8 dogs with portacaval shunt and given antioxidants in combination with co-Q10, TMP and co-Q10 (PCS + TMP + co-Q10 group). Drug usage: TMP, 50 mg/kg/isolation day; coenzyme Q10, 1.5 mg/kg/isolation day; PCS + TMP, given up at the end of 4 wk after operation; and PCS + TMP + co-Q10, given up at the end of 8 wk after operation. The experiment indices: super-peroxide dismutase (SOD), malondialdehyde (MDA), ALT, AST, AKP were all measured before operation, and 8 wk after operation. The liver tissues were obtained in the 4^th week and 8^th week respectively after operation and the changes of hepatic structures were observed under light and electronic microscope.

RESULTS: There were obvious increase of MDA and decrease of SOD in PCS group, which was remarkably different from pre-operation (P < 0.01). In PCS + TMP group, there was no difference between pre-operation and within 4 wk after operation (P > 0.05). But it was remarkably different from PCS group (P < 0.01). Beginning from the 5^th week after operation, we stopped TMP (ligustrazine), as a result, the obvious increase of MDA, rapid decrease of SOD were found, but not different from PCS group (P > 0.05). In PCS + TMP + co-Q10 group, MDA increased slightly, and SOD decreased, but it was superior to that in PCS and PCS + TMP groups. The data in PCS + TMP + co-Q10 group had statistical significance compared to that in PCS + TMP group (P < 0.05) during 4 wk after operation; but from the 5^th to 8^th week, there was a remarkable difference (P < 0.01). The results of ALT, AST and AKP showed remarkable difference between PCS + TMP + co-Q10, PCS group (P < 0.01) and PCS + TMP compared to PCS + TMP + co-Q10 (P < 0.05). After stopping TMP, PCS + TMP were compare d with PCS + TMP + co-Q10 (P < 0.01). The changes in liver structures were fatty degeneration, atrophy and necrosis; decrease in rough surfaced endoplasmic reticulum (RER), mitochondrial swelling, partial mitochondria fusion, disappearance of mitochondrial crista, diminution of Golgi body. The structures of liver cells in PCS + TMP and PCS + TMP + co-Q10 groups were superior to that in PCS group; but in the 8^th week after operation, the liver structural changes had no difference between PCS + TMP and PCS group. The results of light electronic microscopy in PCS + TMP + co-Q10 were better than that in PCS and PCS + TMP groups.

CONCLUSION: The over-activated lipid peroxides reaction may be one of the important factors of hepatic ischemia damage after portacaval shunt; combined use of the antioxidants can enhance the protection from the hepatic ischemia damage.

Key Words: Hepatic ischemia damage; Antioxidants; Portacaval shunt; Lipid peroxides reaction; Malondialdehyde; Superoxide dismutase