Effects of Thermal Stress on Hepatic Melanomacrophages of Eupemphix nattereri (Anura)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise reduces angiotensin II responses in rat femoral veins

The control of blood flow during exercise involves different mechanisms, one of which is the activation of the renin-angiotensin system, which contributes to exercise-induced blood flow redistribution. Moreover, although angiotensin II (Ang II) is considered a potent venoconstrictor agonist, little is known about its effects on the venous bed during exercise. Therefore, the present study aimed to assess the Ang II responses in thefemoral vein taken from sedentary and trained rats at rest or subjected to a single bout of exercise immediately before organ bath experiments. Isolated preparations of femoral veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in an organ bath. In parallel, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as the ETA and ETB receptors, was quantified by real-time PCR in this tissue. The results show that, in the presence of L-NAME, Ang II responses in resting-sedentary animals were higher compared to the other groups. However, this difference disappeared after co-treatment with indomethacin, BQ-123 or BQ-788. Moreover, exercise reduced ppET-1 mRNA expression. These reductions in mRNA expression were more evident in resting-trained animals. In conclusion, either acute or repeated exercise adapts the rat femoral veins, thereby reducing the Ang II responses. This adaptation is masked by the action of locally produced nitric oxide and involves, at least partially, the ETB- mediated release of vasodilator prostanoids. Reductions in endothelin-1 production may also be involved in these exercise-induced modifications of Ang II responses in the femoral vein.

Sex hormones change visceral pigmentation in Eupemphix nattereri (Anura): effects in testicular melanocytes and hepatic melanomacrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polidocanol versus hypertonic glucose for sclerotherapy treatment of reticular veins of the lower limbs: study protocol for a randomized controlled trial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pre- and postoperative evaluation by photoplethysmography in patients receiving surgery for lower-limb varicose veins

Objective. To evaluate the effectiveness of surgery in treating primary varicose veins in the lower limbs by photoplethysmography (PPG) and duplex mapping (DM). Method. Forty-eight lower limbs were clinically evaluated according to the CEAP classification system and subjected to PPG and DM exams. Each limb had a venous refill time (VRT) of <20 seconds and a normal deep vein system (DVS) by DM. Results. The mean pre- and postoperative VRTs were 13.79 and 26.43 seconds, respectively (P < 0.0001). After surgery, 42 limbs (87.50%) had normal results by PPG (VRT > 20 seconds). Four limbs (8.33%) showed improved VRTs, but the VRTs did not reach 20 seconds. In the 2 limbs (4.17%) that maintained their original VRTs, the DM exams showed the presence of insufficient perforating veins. Conclusion. In most cases, PPG allows for a satisfactory evaluation of the outcome of varicose vein surgery.

E2 potentializes benzo(a)pyrene-induced hepatic cytochrome P450 enzyme activities in Nile tilapia at high concentrations

In the aquatic environment, biotransformation enzymes are established biomarkers for assessing PAH exposure in fish, but little is known about the effect of 17β-estradiol (E2) on these enzymes during exposure to benzo(a)pyrene (BaP). In this study, Nile tilapia (Oreochromis niloticus) were exposed for 3, 5, and 10 days to BaP (300 μg L(-1)) and E2 (5 μg L(-1)). These substances were applied isolated or mixed. In the mixture experiment, fish were analyzed pre- and postexposure in order to better understand whether preexposure to the hormone masks the responses activated by PAH or vice versa. Phase I enzymes ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-depenthylase (PROD), and benzyloxyresorufin-O-debenzylase (BROD) activities as well as the phase II enzyme glutathione S-transferase (GST) were analyzed. Isolated E2 treatment decreased EROD activity after 3 days, but this enzyme activity returned to control values after 5 and 10 days of exposure. Isolated BaP treatment significantly induced EROD activity after 3 and 5 days, and the activity returned to control levels after ten exposure days. Combined treatment (E2 + Bap) significantly increased EROD activity, both in the pre- and postexposure. This increase was even higher than in the isolated BaP treatment, suggesting a synergism between these two compounds. When E2 and BaP were used singly, they did not change BROD and PROD activities. However, combined treatment (E2 + Bap) significantly increased PROD activity. Isolated BaP treatment increased GST activity after 10 days. However, this response was not observed in the mixture treatment, suggesting that E2 suppressed the GST induction modulated by BaP. The results put together indicated that E2 altered the biotransformation pathway regarding enzymes activated by BaP in Nile tilapia.

Norepinephrine responses in rat renal and femoral veins are reinforced by vasoconstrictor prostanoids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway.

Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state

To maintain euglycemia in healthy organisms, hepatic glucose production is increased during fasting and decreased during the postprandial period. This whole process is supported by insulin levels. These responses are associated with the insulin signaling pathway and the reduction in the activity of key gluconeogenic enzymes, resulting in a decrease of hepatic glucose production. On the other hand, defects in the liver insulin signaling pathway might promote inadequate suppression of gluconeogenesis, leading to hyperglycemia during fasting and after meals. The hepatocyte nuclear factor 4, the transcription cofactor PGC1-α, and the transcription factor Foxo1 have fundamental roles in regulating gluconeogenesis. The loss of insulin action is associated with the production of pro-inflammatory biomolecules in obesity conditions. Among the molecular mechanisms involved, we emphasize in this review the participation of TRB3 protein (a mammalian homolog of Drosophila tribbles), which is able to inhibit Akt activity and, thereby, maintain Foxo1 activity in the nucleus of hepatocytes, inducing hyperglycemia. In contrast, physical exercise has been shown as an important tool to reduce insulin resistance in the liver by reducing the inflammatory process, including the inhibition of TRB3 and, therefore, suppressing gluconeogenesis. The understanding of these new mechanisms by which physical exercise regulates glucose homeostasis has critical importance for the understanding and prevention of diabetes.

Novel markers of inflammatory response and hepatic dysfunction in canine leishmaniasis

Dogs are the main host of Leishmania infantum, and the clinical presentation may range from asymptomatic to systemic manifestations. The immune mechanisms in infected, but clinically healthy dogs, prevails Th1 response mediated by cytokines. In this sense, adenosine deaminase (ADA) and butyrylcholinesterase (BChE) are considered as key enzymes in several physiological processes, including the modulation of inflammatory process. Considering the variable immune response against Leishmania and the known participation of ADA and BChE, the aim of this study was to assess the relation between these two enzymes with the inflammatory response as well as hepatic function in dogs naturally infected with L. infantum. For this purpose, the activity of ADA and BChE was assessed in sera of 24 dogs naturally infected with L. infantum, plus 17 healthy dogs. The naturally infected dogs had clinical signs compatible with leishmaniasis and sera activities of ADA (P<0.01) and BChE (P<0.05) decreased, when compared to the healthy group. The reduction of ADA activity probably represented an effect on inflammatory response, especially due to the decreased hydrolysis of extracellular adenosine, might in order to protect against tissue damage and, also, setting a down-regulation on pro-inflammatory cytokines. BChE enzyme had no effect on modulating the immune response in leishmaniasis, but it decreased, a fact may related to deficiency of synthesis in the liver. Therefore, ADA and BChE activities reduced probably in order to protect against extra tissue damage and due failure in synthesis, respectively.