Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Oct 2011
Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice.
The antimetastatic potential of thujone, a naturally occurring monoterpene, was evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Administration of thujone (1 mg·(kg body weight)(-1)), prophylactically and simultaneously with tumor induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%, respectively, with an increase in the survival rate (33.67% and 32.16%) of the metastatic tumor bearing animals. ⋯ Thujone treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen-coated microtire plate wells and the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. These results indicate that Thujone can inhibit the lung metastasis of B16F-10 cells through inhibition of tumor cell proliferation, adhesion, and invasion, as well as by regulating expression of MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines and IL-2 in metastatic animals.
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Can. J. Physiol. Pharmacol. · Jul 2011
The effect of alphaxalone-alphadolone, propofol, and pentobarbitone anaesthesia on the β-endorphin and ACTH response to haemorrhage in the pig.
In the literature there appears to be variability in reported levels of certain hormones during haemorrhage, specifically adrenocorticotrophic hormone (ACTH) and β-endorphin. It is possible that this variability may be due to the choice of anaesthetic. Therefore, the effect of 3 common research-only anaesthetic agents (alphaxalone-alphadolone, propofol, and pentobarbitone) on ACTH and β-endorphin levels during haemorrhage was assessed in pigs. ⋯ The increase in heart rate during haemorrhage was significantly different between the alphaxalone-alphadolone and propofol as well as between the propofol and pentobarbitone groups. The drop in blood pressure was only significantly different between the alphaxalone-alphadolone- and propofol-anaesthetized pigs. These results indicate that the choice of anaesthetic agent can affect the hormone response to haemorrhage and may account for the variable hormone levels reported in the published literature to date.
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Can. J. Physiol. Pharmacol. · Jan 2011
Comparative StudyThe role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury.
Cytokines play an important role in the pathophysiology of traumatic brain injury (TBI). This study was designed to determine the effects of administering progesterone (P) and estrogen (E), alone and in combination, on brain water content, blood-brain barrier (BBB) disturbance, and brain level of cytokines following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. ⋯ In the E2+P2-treated group, this level was higher than in the E2-treated group. The brain level of TGF-β was also elevated by the administration of progesterone and estrogen alone, and reduced when the hormones were administered in combination. In conclusion, a combined administration of progesterone and estrogen inhibited the decreasing effects of administration of progesterone and estrogen alone on water content and BBB disruption that mediated to change the proinflammatory cytokines.
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Can. J. Physiol. Pharmacol. · Dec 2010
A low-protein, high-carbohydrate diet increases the adipose lipid content without increasing the glycerol-3-phosphate or fatty acid content in growing rats.
The amount of triacylglycerol (TAG) that accumulates in adipose tissue depends on 2 opposing processes: lipogenesis and lipolysis. We have previously shown that the weight and lipid content of epididymal (EPI) adipose tissue increases in growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The aim of this work was to study the pathways involved in lipogenesis and lipolysis, which ultimately regulate lipid accumulation in the tissue. ⋯ Glycerokinase activity - i.e., the phosphorylation of glycerol from the hydrolysis of endogenous TAG to form G3P - was also not affected in LPHC-fed rats. In contrast, adipocytes from LPHC animals had a reduced lipolytic response when stimulated by norepinephrine, even though the basal adipocyte lipolytic rate was similar for both of the groups. Thus, the results suggest that the reduction of lipolytic activity stimulated by norepinephrine seems essential for the TAG increase observed in the EPI adipose tissue of LPHC animals, probably by impairment of the process of activation of lipolysis by norepinephrine.
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Can. J. Physiol. Pharmacol. · Jun 2010
Endothelins implicated in referred mechanical hyperalgesia associated with colitis induced by TNBS in mice.
This study evaluated the contribution of endothelins to changes in sensitivity to mechanical stimulation of the lower abdomen and hind paw associated with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The frequency of withdrawal responses to 10 consecutive applications of von Frey probes to the lower abdomen (0.07 g) or hind paw (0.4 g) was assessed in male BALB/c mice before and after intracolonic TNBS injection (0.5 mg in 100 microL of 35% ethanol). TNBS (0.5 mg) induced referred mechanical hyperalgesia in the abdomen (response frequencies at 24 h: saline 11.0% +/- 3.1%, TNBS 48.0% +/- 6.9%) and hind paw (frequencies at 24 h: saline 12.5% +/- 4.7%, TNBS 47.1% +/- 7.1%) lasting up to 72 and 48 h, respectively. ⋯ Atrasentan (ETA receptor antagonist; 10 and 30 mg/kg, i.v.) given 24 h after TNBS abolished hind paw and abdominal mechanical hyperalgesia for 2-3 h. A-192621 (ETB receptor antagonist; 20 mg/kg, i.v.) attenuated abdominal mechanical hyperalgesia at the 3 h time point only. Thus, endothelins contribute importantly to abdominal and hind paw referred mechanical hyperalgesia during TNBS-induced colitis mainly through ETA receptor-signaled mechanisms.