ABSTRACT
We investigated the protective effects and possible mechanisms of Aplysin against alcohol-induced liver injury. Rats were given daily either alcohol only (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6 weeks, the effects of Aplysin were assessed in terms of changes in histology, biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed through measurements of lipid peroxidation, antioxidant defense systems, expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We found that Aplysin significantly protected the liver against alcohol-induced oxidative injury, evidenced by improved hepatic histological structure, inhibited alcohol-induced elevation of serum biochemical indices, attenuated extents of hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol-induced oxidative stress as illustrated by the revivification of erythrocyte membrane fluidity, the attenuation of glutathione depletion, the restoration of antioxidase activities, and reduced malondialdehyde overproduction. Furthermore, the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly up-regulated. These findings suggest that Aplysin provides significant protection against alcohol-induced liver injury, possibly through alleviating oxidative damage and modulating endogenous apoptosis-related genes expression. PRACTICAL APPLICATION: Many natural components derived from alga have been used in the food, cosmetics, and biomedicine industries. Aplysin, a marine bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which could effectively protect against alcohol-induced liver injury, might be a potential natural sources for preventing alcoholic liver damage.
Subject(s)
Apoptosis/drug effects , Chemical and Drug Induced Liver Injury/drug therapy , Ethanol/adverse effects , Hydrocarbons, Brominated/pharmacology , Oxidative Stress/drug effects , Sesquiterpenes/pharmacology , Animals , Antioxidants/pharmacology , Caspase 3/metabolism , Cytochrome P-450 CYP2E1/metabolism , DNA Damage/drug effects , Erythrocyte Membrane/drug effects , Gene Expression/drug effects , Glutathione/metabolism , Laurencia , Lipid Peroxidation/drug effects , Liver/drug effects , Male , Malondialdehyde/metabolism , Plant Extracts , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, WistarABSTRACT
Glioma is one of the most common malignancies in the world. However, an effective regiment is lacking. Increasing evidence indicated that PI3K/AKT signaling is critical for the survival of glioma. In this study, we aimed to study the effect of aplysin on the survival and proliferation of GL26 glioma cells and the involved mechanisms. The data showed that aplysin suppressed the viability of glioma cells in both dose- and time-dependent manners. It also induced G0/G1 arrest and apoptosis in glioma cells. Western blot assays revealed that aplysin treatment changed p-AKT expression by impairing the formation of Heat shock protein 90/AKT complex. Aplysin significantly increased the survival time of mice-bearing glioma and reduced the weights of the established gliomas. Collectively, aplysin can inhibit the proliferation of GL26 glioma cells and induce apoptosis in vitro, perhaps through suppressing PI3K/AKT pathway. It can also inhibit glioma growth in vivo and prolong the survival of mice. Thus, aplysin may be a novel therapeutic drug for glioma.
