geranylgeranylacetone and Hypoxia

Teprenone (geranylgeranylacetone) is one kind of safe and effective agent in gastrointestinal mucosa, which have been widely used in human and veterinary, but rarely used in aquaculture animals. In this study, Lateolabrax maculatus, an important economic fish species in southern China, was taken as the object of study to investigate the protective effect of teprenone on intestinal stress. The present study was designed to investigate the potential mechanism underlying the protection offered by teprenone to protect the gastrointestinal tract against hypoxia and reoxygenation injury of L. maculatus. (a) For oxidative stress parameters, SOD, CAT, and T-AOC in control group were higher than those in teprenone group. MDA content was significantly higher than that in teprenone group at N and 12h time points in intestine (P < 0.05), and at 12, 24, and 48 h time points in stomach. (b) For immune-associated proteins, LZM activity in the control group was lower than that in the teprenone group, and the difference between the two groups in stomach and intestine was significant at 12.48 h and 6.48 h time points, respectively (P < 0.05). Compared with time point N, the content of HSP70 in the control group increased at 0 h in intestine. At 0-48 h, intestine HSP70 content in the control group showed a gradually decreasing trend, which was higher than that in the teprenone group. (c) For apoptosis-related factors, the activity of Cyt-C, caspase9, and caspase3 increased first and then decreased in both groups. The content of Cyt-C in the control group was significantly higher than that in the teprenone group at N-3.6 h, and 3.48 h time points in stomach and intestine, respectively (P<0.05). The activity of caspase9 and caspase3 was higher than that in the teprenone group at N-48 h. Results indicated that acute hypoxia and reoxygenation cause the expression levels of oxidative stress and apoptosis-related factors in the stomach and intestine increased first and then decreased within 0-48 h. Acute hypoxia and reoxygenation also that causes the level of nonspecific immunity decreased first and then increased. A total of 400-mg/kg treatment of teprenone can protect stomach and intestinal tissues to a certain extent. It can effectively protect oxidative stress and apoptosis within 0-48 h after acute hypoxia and reoxygenation and enhance non-specific immunity.

Topics: Animals; Apoptosis; Diterpenes; HSP70 Heat-Shock Proteins; Hypoxia; Intestines; Perciformes; Stress, Physiological

It has been shown that induction of HSP70 by administration of geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion injury. The present study was performed to determine the effect of GGA on the survival of mice and on brain damage under acute hypobaric hypoxia. The data showed that the mice injected with GGA survived significantly longer than control animals (survival time of 9.55 +/- 3.12 min, n = 16 vs. controls at 4.28 +/- 4.29 min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of the hippocampus and the cortex induced by sublethal hypoxia for 6 h could be attenuated by preinjection with GGA, especially in the CA2 and CA3 regions of the hippocampus. In addition, the activity of nitric oxide synthase (NOS) of the hippocampus and the cortex was increased after exposure to sublethal hypoxia for 6 h but could be inhibited by the preinjection of GGA. Furthermore, the expression of HSP70 was significantly increased at 1 h after GGA injection. These results suggest that administration of GGA improved survival rate and prevented acute hypoxic damage to the brain and that the underlying mechanism involved induction of HSP70 and inhibition of NOS activity.

Topics: Acclimatization; Animals; Brain; Cerebral Cortex; Diterpenes; Hippocampus; HSP70 Heat-Shock Proteins; Hypoxia; Male; Mice; Nitric Oxide Synthase; Survival Rate