Hemin protects against hippocampal damage following orthotopic autologous liver transplantation in adult rats.

Abstract

Induction of heme oxygenase-1 (HO-1) has been widely accepted to be neuro-protective. This study aimed to examine whether hemin (a HO-1 inducer) attenuates neuronal damage in the hippocampus induced by orthotopic autologous liver transplantation (OALT) in adult rats. Rats were randomly allocated into four groups (n=8 each): (i) Sham control group; (ii) OALT model group; (iii) Hemin+OALT group, with intra-peritoneal (i.p.) injection of hemin (5 mg/kg) 24 hours (h) before the OALT; and (iv) ZnPP (a HO-1 inhibitor)+OALT group, with i.p. injection of ZnPP (32 mg/kg) 24h before the OALT. Twenty four hours after the surgery, the hippocampal tissues were collected for electron microscopic examination and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis. The levels of hippocampal HO-1 protein and serum S-100β, the concentrations of regional tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-10), as well as the status of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the hippocampus were assessed. Rats suffered severe neuronal damage in the hippocampus after OALT, mainly in apoptosis. Pre-treatment with hemin obviously alleviated the damage; up-regulated the HO-1 protein level; inhibited the release of TNF-α, IL-6 and MDA; and promoted the activities of SOD, CAT and IL-10; however, pre-treatment with ZnPP did not exhibit the opposite effect, except that a marked increase in serum S-100β level was detected. Hemin up-regulated the expression of HO-1 and attenuated hippocampal neuronal damage induced by OALT.