Oxidative stress inducers potentiate 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated pre-cardiac edema in larval zebrafish.

We reported the involvement of oxidative stress and prostaglandins including thromboxane and prostacyclin in pre-cardiac edema (early edema) caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While the involvement of oxidative stress in TCDD-induced toxicity has been frequently reported, the mechanism of its action is still unclear. In the present study, oxidative stress inducers including paraquat, hydrogen peroxide (H2O2) and rotenone augmented early edema (edema) induced by a low concentration of TCDD (0.1 ppb) at 55 hr post fertilization (hpf), while each of them alone did not cause edema. Edema caused by TCDD plus oxidative stress inducers was almost abolished by antioxidants, an antagonist for thromboxane receptor (ICI-192,605) and an agonist for prostacyclin receptor (beraprost), suggesting that the site of action of these inducers was in the regular signaling pathway after activation of aryl hydrocarbon receptor type 2 (AHR2) by TCDD. Oxidative stress inducers also enhanced edema caused by an agonist for the thromboxane receptor (U46619), and the enhancement was also inhibited by antioxidants. Sulforaphane and auranofin, activators of Nrf2 that is a master regulator of anti-oxidative response, did not affect U46619-evoked edema but almost abolished TCDD-induced edema and potentiation by paraquat in both TCDD- and U46619-induced edema. Taken together, the results suggest that oxidative stress augments pre-cardiac edema caused by TCDD via activation of thromboxane receptor-mediated signaling in developing zebrafish. As paraquat and other oxidative stress inducers used also are environmental pollutants, interaction between dioxin-like compounds and exogenous source of oxidative stress should also be considered.

Selenium-induced teratogenicity in Sacramento splittail (Pogonichthys macrolepidotus).

Selenium is a potent reproductive and teratogenic environmental contaminant and there are concerns over possible reproductive effects of selenium on the Sacramento splittail (Pogonichthys macrolepidotus) population, a threatened species, in California, USA. In this study, the teratogenic effects of selenium were examined in splittail embryos exposed to 0.0, 5.0, and 15.0 mg l(-1) sodium selenite for 48-h at 18.0 degrees C under static conditions, with renewal every 12 h. Embryo development was evaluated daily for abnormalities from initiation of exposure (stage 27) to initiation of exogenous feeding. At the end of evaluation, prelarvae were preserved for histological analysis. There were no significant differences in mortality or hatching success between control and exposed embryos. Exposed fish had pericardial edema and deformities of skeletal tissues (loss of tail, lordosis, scoliosis, and kyphosis). Other histological alterations were limited to dysplasia, hyperplasia and metaplasia of skeletal tissues in the deformed fish. This study showed that a short exposure of embryos during somite development has significant effects on the musculoskeletal development.

Myocardial edema and compromised left ventricular function attributable to dirofilariasis and cardiopulmonary bypass in dogs.

We investigated the relation between left ventricular dysfunction and myocardial edema in dogs with heartworm (Dirofilaria immitis) infection that were undergoing cardiopulmonary bypass. Dogs with and without D immitis were anesthetized by continuous thiopental infusion and were mechanically ventilated. Sonomicrometry crystals were placed on the long and short axes of the left ventricle, and a Millar pressure transducer was placed in the left ventricular chamber. Pressure-volume loops were digitized and continuously recorded. Dogs with and without D immitis were placed on standard hypothermic cardiopulmonary bypass, with 1 hour of aortic cross-clamp. Wet-to-dry weight ratio corrected for residual blood volume was used to quantitate the volume of myocardial edema. Preload recruitable stroke work was used as a preload-independent index of systolic function. Tau, the isovolumic relaxation time constant, was determined to assess diastolic relaxation. Dogs with D immitis had increased baseline myocardial wet-to-dry weight ratio. After cardiopulmonary bypass, myocardial edema increased in all dogs. Acute edema attributable to cardiopulmonary bypass decreased preload recruitable stroke work in all dogs of both groups, and dogs with D immitis could not be weaned from cardiopulmonary bypass. Myocardial edema increased diastolic relaxation times (tau) in dogs with and without D immitis. We conclude that cardiopulmonary bypass and heartworm infection induce myocardial edema. This edema compromises left ventricular systolic and diastolic function making D immitis an important confounding factor in weaning dogs from cardiopulmonary bypass.