Garcinia dulcis Extract Alleviates Inflammation in Kidney and Liver of the 2-Kidney-1-Clip Hypertensive rat.

Garcinia dulcis (GD) extract possesses anti-hypertensive property that are poorly characterized. This study aimed to investigate an anti-inflammatory effect of GD flower extract in the 2-kidney-1-clip (2K1C) hypertensive compared to sham operative (SO) rat. Male Wistar rats were divided into 2 groups; the 2K1C group in which a silver clip was placed around renal artery to induce hypertension, and the SO normotensive group. Four weeks later, each group of rats were further divided into 2 subgroups, each subgroup was orally gavaged of either corn oil (vehicle) or 50 mg/kg BW GD extract daily for 4 weeks. The malondialdehyde (MDA) levels in serum, liver, and kidney were determined. Hematoxylin and eosin staining was carried out for histological examination, Periodic acid - Schiff staining for glomerular injury, Masson's trichrome staining for renal fibrosis, and immunohistochemistry for either tumor necrosis factor alpha (TNF-α) or endothelial nitric oxide synthase (eNOS) investigation. Taken together, our results demonstrated that GD flower extract decreased the MDA level in both serum and liver and kidney tissue and suppressed the expression of TNF-α in both liver and kidney of 2K1C hypertensive rats. Mesangial cell proliferation, expansion of mesangial matrix, widening Bowman's capsule space, congestion of glomerular capillary and vessel, cloudy swelling of renal tubular epithelial cell, and renal fibrosis were observed in the kidneys of 2K1C rats. Therefore, we concluded that GD flower extract can alleviate liver and kidney inflammation in which partially attenuates the glomerular injury in the 2K1C rat.

Cardiovascular Protective Effect of Garcinia dulcis Flower Acetone Extract in 2-Kidney-1-Clip Hypertensive Rats.

Morelloflavone and camboginol are bioactive compounds purified from Garcinia dulcis (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was to examine the cardiovascular protective effect of GD flower acetone extract in 2-kidney-1-clip (2K1C) hypertensive rats. Male Wistar rats underwent 2K1C or sham operation (SO) and were housed for 4 weeks. Each group of rats, then, was further divided into 2 subgroups receiving oral administration of either 50 mg/kg BW GD extract or corn oil (vehicle) daily for 4 weeks. Noninvasive blood pressure (BP) and body weight were measured weekly throughout the study. Subsequently, the invasive measurement of arterial BP and the heart rate were determined in all anesthetized rats. The baroreceptor reflex sensitivity (BRS) was investigated by injection of either phenylephrine or sodium nitroprusside for bradycardia or tachycardia response, respectively. Histological examination of the heart and thoracic aorta was also performed in order to investigate the general morphology and the tumor necrosis factor alpha (TNF-α) expression. We found that the GD flower extract significantly diminished the BP and restored the impaired BRS. Moreover, it also decreased the TNF-α expression in the cardiac muscle and thoracic aorta of 2K1C when compared to the SO group. Taken together, our data showed that GD flower extract exhibits the cardiovascular protective effect in the 2K1C hypertensive rats.

Daily consumption of monosodium glutamate pronounced hypertension and altered renal excretory function in normotensive and hypertensive rats.

This study aimed to investigate the effects of monosodium glutamate (MSG) on the levels of arterial blood pressure (ABP) and renal excretory function. Male Wistar rats were divided into 2 groups (n = 24 each) namely sham operation (SO) and 2-kidneys-1-clip (2K1C) to develop the normotensive and hypertensive model, respectively. Four weeks after the operation, each group of rats were further divided into 4 subgroups (n = 6 each) which were orally administered of either distilled water or MSG at the doses of 80, 160, or 320 mg/kg BW/day once a day for 8 weeks. The body weight, the 24-hour water intake, and the 24-hour urine output were recorded weekly. Then, each rat was anesthetized and the ABP was measured via carotid artery. The renal excretory function was examined by using the clearance technique to measure the levels of the glomerular filtration rate and the renal blood flow. The levels of serum malondialdehyde (MDA) as a marker of oxidative stress were analyzed. The expression of tumor necrosis factor alpha (TNF-α) in the kidneys was also investigated using immunohistochemistry. It was found that all doses of MSG significantly increased the ABP in both SO and 2K1C groups. All doses of MSG significantly increased the serum MDA levels and the expression of TNF-α in the kidneys of the SO groups. Long-term intake of 320 mg/kg BW MSG significantly decreased the renal excretion of salt and water in both SO and 2K1C groups. As a whole, this study demonstrated that MSG consumption contributed to an increase in oxidative stress which could lead to alterations in the cardiovascular and renal function.

P2Y6 receptors are involved in mediating the effect of inactivated avian influenza virus H5N1 on IL-6 & CXCL8 mRNA expression in respiratory epithelium.

One of the key pathophysiologies of H5N1 infection is excessive proinflammatory cytokine response (cytokine storm) characterized by increases in IFN-ß, TNF-α, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced cytokine release can occur via an infection-independent mechanism, however, detail of the cellular signaling involved is poorly understood. To elucidate this mechanism, the effect of inactivated (ß-propiolactone-treated) H5N1 on the cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL-6 and CXCL8 but not TNF-α, CCL5 or CXCL10. This effect of the inactivated-H5N1 was inhibited by sialic acid receptor inhibitor (α-2,3 sialidase), adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C inhibitors (BIM and Gö6976) and cell-permeant Ca2+ chelator (BAPTA-AM). Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580) and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125, whereas SN-50, an inhibitor of NF-κB, inhibited the effect of virus on mRNA expression of both of IL-6 and CXCL8. Taken together, our data suggest that, without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and α-2,3 sialic acid receptors at the cell membrane of host cells, and involves activation of P2Y6 purinergic receptors.

Low gamma wave oscillations in the striatum of mice following morphine administration.

Functional role of the striatum in motor control has been widely studied. In addition, its involvement in reward function as a brain area in the dopamine system has also been mentioned. However, neural signaling in the striatum in response to consumption of emotional enhancing substances remained to be explored. This study aimed to investigate local field potential (LFP) of the striatum following morphine administration. Male Swiss albino mice implanted with electrode into the striatum were given an intraperitoneal injection of either saline or morphine (5 or 15 mg/kg). LFP and locomotor activity of individual animals were simultaneously recorded in the recording chamber following the administration. The inspection of LFP tracings revealed the increase in fast wave induced by morphine particularly at a high dose. Statistical analyses were performed using a one way ANOVA followed by Tukey post hoc test. Frequency analysis using Fast Fourier transform also confirmed a significant elevation of low gamma (30-44.9 Hz) activity. When analyzed in time domain, significant increase in low gamma power was observed from the 15th to 65th min following 15 mg/kg morphine treatment. Moreover, morphine treatment also exhibited a stimulating effect on locomotor speed. However, regression analyses revealed no significant correlation between low gamma power and locomotor speed. In summary, this study demonstrated the increase in low gamma oscillation in the striatum and this effect was not associated with locomotor activity of animals. Thus, it is possible that low gamma oscillation induced by morphine treatment is related with the reward function.

The normal choroidal thickness in southern Thailand.

OBJECTIVE: To investigate the association between subfoveal choroidal thickness in healthy southern Thailand volunteers and age, axial length, and refractive error. SUBJECTS AND METHODS: This was a prospective cross-sectional case series. A total of 210 eyes of 105 healthy volunteers (86 women, age 23-83 years) in southern Thailand were examined with enhanced depth-imaging optical coherence tomography. Subjects with systemic diseases that may affect the choroidal vascular blood vessels, such as diabetes, impaired renal function, and hypertension, were excluded. Refractive error and axial length were measured by autorefractometry and an IOLMaster, respectively. Subfoveal choroidal thickness was measured from the outer border of the retinal pigment epithelium to the inner scleral border in the subfoveal area. RESULTS: The mean subfoveal choroidal thickness was 279.4±75.49 µm, and the mean age was 46.4±16.45 years. Subfoveal choroidal thickness was negatively correlated with age (r (2)=0.33, P<0.0001) and axial length (r (2)=0.02, P<0.02). Multivariable regression analysis showed subfoveal choroidal thickness was positively and negatively correlated with a spherical equivalent refractive error and axial length, respectively, when adjusted for age. CONCLUSION: Age is the most important factor in choroidal thickness rather than axial length and refractive error. Subfoval choroidal thickness was decreased 2.67 µm every year and 14.59 µm with 1 mm increase in axial length.

Acute effects of candesartan on rat renal haemodynamics and proximal tubular reabsorption.

1. The effects of the specific angiotensin II receptor type I (AT1) antagonist candesartan on renal proximal tubular sodium transport were studied using lithium clearance. The effects of candesartan on mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR) and sodium and potassium excretion were also investigated. 2. Male Wistar rats were anaesthetized with Inactin (thiobutabarbital sodium; Sigma, St Louis, MO, USA). Clearance markers (8% polyfructosan, 1% para-aminohippuric acid and 4 mmol/l lithium chloride) were given into a jugular vein at the rate of 1.6 mL/h per 100 g bodyweight. Candesartan was given as bolus injection (0.01, 0.1, 0.2, 0.5 and 1.0 mg/kg) followed by 60 min continuous infusion at a rate of 0.5, 5, 10, 25 and 50 microg/min per kg, respectively. 3. The non-depressor dose of candesartan (0.01 mg/kg) did not alter RPF or GFR, whereas diuresis, natriuresis and kaliuresis were observed. The higher doses of candesartan reduced MABP, RPF and GFR, although diuresis, natriuresis and kaliuresis were still observed. 4. Renal tubular sodium and water reabsorption were inhibited after intravenous administration of candesartan independently of an alteration in arterial pressure. Lithium clearance data indicate that the site of inhibition was in the proximal nephron segment.

Regulation of renal proximal fluid uptake by luminal and peritubular angiotensin II.

INTRODUCTION: Angiotensin II (Ang II), when administered to either tubular lumen or peritubular capillary, exerts a biphasic action on proximal fluid uptake rate. At low concentrations, (10(-12)-10(-10) M) Ang II stimulates fluid transport, whereas higher doses (>10(-9) M) inhibit. Ang II is secreted into the lumen in the proximal tubule and the concentration of Ang II in the proximal lumen has been reported to be in the nanomolar range, 100-1,000 times higher than in peritubular blood. We investigated the regulation of renal proximal fluid transport by luminal (predominantly locally produced) and peritubular capillary (circulatory) Ang II in anaesthetised rats, using a selective AT(1)-receptor antagonist, candesartan. METHODS: Experiments were performed in inactin-anaesthetised male Wistar rats. Proximal fluid uptake rate was measured using computerised capture and analysis of shrinking-split droplet microperfusion in response to either luminal addition or luminal addition with simultaneously peritubular capillary perfusion of 10(-8) M candesartan. RESULTS: Luminal addition of candesartan (10(-8) M) decreased fluid absorption by 19-25%. Perfusion of the peritubular capillaries with an electrolyte solution (containing no Ang II) reduced fluid uptake by 27%, and blockade of the peritubular actions of Ang II by addition of candesartan (10(-8) M) resulted in 33% decrease in fluid uptake. However, when candesartan (10(-8) M) was added to both luminal and capillary perfusates, there was a 43% reduction in fluid transport when compared with initial values. CONCLUSION: These results suggest that the presence of endogenous Ang II in both peritubular blood and luminal fluid is important for maximal expression of the stimulatory influence of this peptide on proximal tubule fluid uptake.