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The role of Nrf2 in selected models of liver injury
Mezera, Vojtěch ; Červinková, Zuzana (advisor) ; Brůha, Radan (referee) ; Ehrmann, Jiří (referee)
The role of Nrf2 in selected models of liver injury Oxidative stress accompanies various forms of liver injury, including liver resection and toxic liver injury. Two-thirds partial hepatectomy (PHx) is an established model for the study of liver regeneration after resection. We tested the effect of epigallocatechin gallate (EGCG), a green tea antioxidant, on the early phase of liver regeneration after PHx. Male Wistar rats received either water for injections or EGCG for 3 consecutive days and then were subjected either to laparotomy or hepatectomy. We observed a lower accumulation of bromodeoxyuridine pointing to lower DNA synthesis in hepatectomized rats receiving EGCG in a dose of 50 mg/kg than in hepatectomized rats treated with water. The activity of caspases 3/7, expression of p-p53 and tissue levels of IL-6 displayed a similar trend. EGCG in a dose of 20 mg/kg had no such effects. Next, male Wistar rats were subjected either to PHx or laparotomy. Twenty-four hours after the surgery, hepatocytes were isolated and treated with various concentrations of EGCG for 24 h. Morphological criteria, cell viability tests, and albumin synthesis revealed toxicity starting at 10 µmol/L. DNA synthesis was higher in hepatocytes isolated from rats after PHx and inhibited by EGCG. Furthermore, EGCG increased...
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