Bracteanolide A abrogates oxidative stress-induced cellular damage and protects against hepatic ischemia and reperfusion injury in rats.

Liver diseases, including viral hepatitis, liver cirrhosis, and liver cancer, mostly remain silent until the late stages and pose a continuing threat to millions of people worldwide. Liver transplantation is the most appropriate solution in the case of liver failure, but it is associated with hepatic ischemia and reperfusion (I/R) injury which severely reduces the prognosis of the patients. In order to ameliorate I/R injury, we investigated the potential of bracteanolide A, from the herb Tradescantia albiflora Kunth in protecting the liver from I/R injury. We first determined the protective effect of bracteanolide A against oxidative stress and DNA damage using HepG2 hepatocyte cell line and then assessed the levels of inflammatory cytokines and antioxidant proteins in response to hepatic insult using an animal model of hepatic I/R injury. The results showed bracteanolide A greatly enhanced cell survival and decreased reactive oxygen species (ROS) production under H2O2 induction. It also upregulated the expression of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and its downstream cytoprotective proteins NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Bracteanolide A effectively reduced the severity of liver lesions in I/R-injured rats revealed by histological analysis and significantly decreased the levels of alanine transaminase (ALT), aspartate transaminase (AST), cyclooxygenase-2, and inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Bracteanolide A preconditioning effectively protected the liver from I/R damage in the animal model, and this easily applied procedure may provide a new means to ameliorate hepatic I/R injury during liver surgeries.

Ergostatrien-3ß-ol (EK100) from Antrodia camphorata Attenuates Oxidative Stress, Inflammation, and Liver Injury In Vitro and In Vivo.

Hepatic ischemia/reperfusion (IR) injury is a complication that occurs during liver surgery, whereby hepatic tissue is injured by oxygen deficiency during ischemia, then further damaged by a cascade of inflammatory and oxidative insults when blood is resupplied during reperfusion. Antrodia camphorata is an indigenous fungus in Taiwan and an esteemed Chinese herbal medicine with various bioactivities. This study examined the effect of ergostatrien-3ß-ol (EK100), an active compound found in both the fruiting body and mycelia of A. camphorata, on IR injury pathologies in rats and cell models of oxidative and inflammatory stress. Male Sprague-Dawley rats were randomly assigned to receive a vehicle or 5 mg/kg EK100 prior to hepatic IR injury induced by 1 h ischemia followed by 24 h reperfusion, or a sham operation. RAW 264.7 murine macrophages and HepG2 hepatocytes were pretreated with EK100, then inflammation was induced with lipopolysaccharides in the former and oxidative stress was induced with hydrogen peroxide in the latter. EK100 decreased IR-induced elevation in serum levels of alanine aminotransferase and aspartate aminotransferase and lowered levels of the inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß. In addition, EK100 significantly reduced hepatic mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, as well as nitrite production and iNOS gene expression in both hepatocyte and macrophage cell lines. We demonstrated that EK100 exhibits potent protec-tion against hepatic IR injury, which may be used to design strategies to ameliorate liver damage during liver surgery.

Preconditioning somatothermal stimulation on Qimen (LR14) reduces hepatic ischemia/reperfusion injury in rats.

BACKGROUND: In human beings or animals, ischemia/reperfusion (I/R) injury of the liver may occur in many clinical conditions, such as circulating shock, liver transplantation and surgery and several other pathological conditions. I/R injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators. This study aimed at studying the effects of local somatothermal stimulation preconditioning on the right Qimen (LR14) on hepatic I/R injury in rats. METHODS: Eighteen male Sprague-Dawley rats were randomly divided into three groups. The rats were preconditioned with thermal tolerance study, which included one dose of local somatothermal stimulation (LSTS) on right Qimen (LR14) at an interval of 12 h, followed by hepatic ischemia for 60 min and then reperfusion for 60 min. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been used to assess the liver functions, and liver tissues were taken for the measurements such as malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxidase dismutase (SOD), and myeloperoxidase (MPO). RESULTS: The results show that the plasma ALT and AST activities were higher in the I/R group than in the control group. In addition, the plasma ALT and AST activities decreased in the groups that received LSTS. The hepatic SOD levels reduced significantly by I/R injury. Moreover, the hepatic MPO activity significantly increased by I/R injury while it decreased in the groups given LSTS. CONCLUSIONS: Our findings show that LSTS provides a protective effects on the liver from the I/R injury. Therefore, LSTS might offer an easy and inexpensive intervention for patients who have suffered from I/R of the liver especially in the process of hepatotomy and hepatic transplantation.

Preconditioned hyperbaric oxygenation protects the liver against ischemia-reperfusion injury in rats.

Hyperbaric oxygen (HBO) therapy is an effective adjunct in treating ischemia-reperfusion (I/R) injury of brain, small intestine, testis, and crushing extremities. This study was designed to test the hypotheses that preconditioning the rats with HBO could protect the liver against subsequent I/R injury. Daily treatment with one-dose HBO (90 min, 2.5 ATA) was brought about for male Sprague Dawley rats for 1 to 3 days before an I/R injury of liver. Hepatic expression of heat-shock protein 70 (Hsp70), total concentration of glutathione (GSH), activity of catalase, superoxide dismutase (SOD), and serum AST and ALT were estimated before and after HBO, as well as after I/R injury. The results showed that activity of hepatic catalase was decreased by one dose, but not three doses, of HBO as compared with baseline data. However, hepatic Hsp70 expression fluctuated insignificantly. AST and ALT increase less in rats preconditioned with one-dose HBO as compared with those without HBO or with three-dose HBO. Our results showed preconditioning by one-dose HBO protects rat liver against subsequent ischemia-reperfusion injury.

Salvianolic acid B enhances in vitro angiogenesis and improves skin flap survival in Sprague-Dawley rats.

Insufficient angiogenesis and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin flap failure. Salvianolic acid B (Sal B), isolated from Salvia miltiorrhiza, has been reported to enhance angiogenesis in vitro. This study was aimed to determine the efficacy of Sal B on ischemia-reperfusion injury of the skin flap in Sprague-Dawley rats. Sal B was administered intraperitoneally 2 h before operation, and on the 2nd and 4th days after surgical elevation of an extended epigastric adipocutaneous flap (5 x 7 cm) in ketamine-anesthetized rats. Flap ischemia was achieved by ligating the right superficial epigastric artery and vein and clamping the left superficial epigastric artery and vein for 3 h and then released. Percentage of flap necrosis area (FNA) and plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and malondialdehyde were measured at 7 days after the operation. Animals were divided into six groups, including: vehicle, Sal B low dose (5 mg/kg), Sal B high dose (50 mg/kg) and each with [mesh(+)] or without mesh [mesh(-)] placement. In the three groups with mesh(+), FNA in control flaps was 53.7 +/- 6.9%, whereas low-dose and high-dose Sal B significantly improved flap survival with FNA 27.4 +/- 3.8% and 25.3 +/- 4.3%, respectively (P < 0.05, one-way ANOVA). In the three groups with mesh(-), control flaps were 35.9 +/- 4.5%, whereas high-dose Sal B also significantly improved flap survival with FNA 17.9 +/- 4.7% (P < 0.05, one-way ANOVA). There were no differences in aspartate aminotransferase, alanine aminotransferase, creatinine, or malondialdehyde between groups. We conclude that Sal B attenuates ischemia-reperfusion injury of skin flap, and provides therapeutic potential in reconstructive plastic surgery.