Vanillylacetone attenuates cadmium chloride-induced hippocampal damage and memory loss through up-regulation of nuclear factor erythroid 2-related factor 2 gene and protein expression.

JOURNAL/nrgr/04.03/01300535-202412000-00030/figure1/v/2024-04-08T165401Z/r/image-tiff Memory loss and dementia are major public health concerns with a substantial economic burden. Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment. To investigate whether the antioxidant and anti-inflammatory compound vanillylacetone (zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride (CdCl2) administration in rats, we explored the potential involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is known to modulate oxidative stress and inflammation. Sixty healthy male Wistar rats were divided into five groups: vehicle-treated (control), vanillylacetone, CdCl2, vanillylacetone + CdCl2, vanillylacetone + CdCl2 + brusatol (a selective pharmacological Nrf2 inhibitor) groups. Vanillylacetone effectively attenuated CdCl2-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test. Additionally, vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, intracellular cell adhesive molecules) and apoptosis biomarkers (Bax and cleaved caspase-3). The control and CdCl2-treated groups treated with vanillylacetone showed reduced generation of reactive oxygen species, decreased malondialdehyde levels, and increased superoxide dismutase and glutathione activities, along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue. All the protective effects of vanillylacetone were substantially blocked by the co-administration of brusatol (a selective Nrf2 inhibitor). Vanillylacetone mitigated hippocampal damage and memory loss induced by CdCl2, at least in part, by activating the nuclear transcription factor Nrf2. Additionally, vanillylacetone exerted its potent antioxidant and anti-inflammatory actions.

Ghrelin prevents cardiac cell apoptosis during cardiac remodelling post experimentally induced myocardial infarction in rats via activation of Raf-MEK1/2-ERK1/2 signalling.

CONTEXT: Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear. OBJECTIVE: To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway. MATERIALS AND METHODS: Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 µg/kg) was administered for 21 days, starting one-day post-MI. RESULTS: Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser338), phospho-MEK1/2 (Ser217/221), phospho-ERK1/2 (Thr202/Tyr204), and of their downstream target p-BAD (Ser112) and inhibited the cleavage of caspase-3. Concomitantly, ghrelin prevented the increases in the levels of fibrotic markers, including α-smooth muscle actin (α-SMA), metalloproteinase-9 (MPP-9), and type III collagen. CONCLUSION: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.

Acylated ghrelin protects aorta damage post-MI via activation of eNOS and inhibition of angiotensin-converting enzyme induced activation of NAD(P)H-dependent oxidase.

NAD(P)H dependent oxidase derived-reactive oxygen species (ROS) due to activation of the renin-angiotensin-aldosterone system (RAAS) in blood vessels postmyocardial infarction MI or during the HF leads to endothelium dysfunction and enhanced apoptosis. Acylated ghrelin (AG) is a well-reported cardioprotective and antiapoptotic agent for the heart. AG receptors are widely distributed in most of blood vessels, suggesting a role in the regulation of endothelial function and survival. This study investigated if AG can protect aorta of rats' postmyocardial infarction (MI)-induced damage and endothelial dysfunction. Adult male rats were divided into four groups of (1) Sham, (2) Sham + AG, (3) MI, and (4) MI + AG. Vehicle (normal saline) or AG (100 µ/kg) was administered to rats for 21 consecutive days, after which, numerous biochemical markers were detected by blot. Both histological and electron microscope studies were carried on aortic samples from MI-induced rats. AG increased protein levels of both total and phosphorylated forms of endothelial nitric oxide synthase (eNOS and p-eNOS, respectively). Only in MI-treated rats, AG prevented the decreases in the levels of reduced glutathione (GSH) and superoxide dismutase (SOD) and lowered levels of malondialdehyde (MDA) and glutathione disulfide (GSSG). Concomitantly, it lowered the increased protein levels of angiotensin-converting enzyme (ACE), p22phox and cleaved caspase-3 and prevented the aorta histological and ultrustructural abnormalities induced by MI.

Ghrelin improves the fine structure of atrial natriuretic factor (ANF) granules and intercalated disc junctions in experimentally-induced myocardial infarction in rats / La grelina mejora las estructuras finas de los gránulos de factor natriurético atrial (ANF) y las uniones intercaladas de disco en el infarto de miocardio inducido experimentalmente en ratas

Ghrelin is a novel growth hormone-releasing peptide administered to treat myocardial infarction (MI). However, the underlying mechanism of its protective effects against MI remains unclear. A total of sixty healthy Sprague Dawley male rats were included. The first one is the sham-operated control group were the rats that underwent the same surgical used to induce MI but without tying the left anterior descending coronary artery (LAD) and received normal saline (0.5 ml) as vehicle; the second MI model group were rats with LAD ligation and received normal saline (0. 5 ml) and the third one is MI+ghrelin group were rats that were exposed to surgery to induce MI but received ghrelin (100 µ/kg, orally, 2x/day). At the end of the experiment after 21 days post-MI, rats were sacrificed and processed for ultrastructural demonstration. Our experiment showed that ghrelin inhibited cardiomyocyte apoptosis. Concomitant administration of ghrelin with MI treated rats of this study appeared to show a considerable protection of the atrial tissues. This study revealed that the sarcoplasm was occupied by normal myofibrils with clear striations and others appeared with minor disruption. Normal distribution of atrionatriuretic factor (ANF) granules and well preserved mitochondrial integrity (preserved cristae, normal size and shape), nucleus chromatin arrangement and striated pattern of clear bands (Z and H) compared to the MI group. Intact intercalated disc with clear identification of fully formed fascia adherence and desmosomes with a reconstruction of gap junction (nexus) was also noticed. Atrial myocytes after myocardial infarction is often associated with subsequent heart failure, which could lead to a fatal outcome. In a rat model of experimental myocardial infarction, peripheral ghrelin administration attenuated myocyte dysfunction, well-preserved desmosome, adherent and gap junction of the intercalated disc and normally distributed ANF granules.

La grelina es un nuevo péptido liberador de hormona de crecimiento administrado para tratar el infarto de miocardio (IM). Sin embargo, el mecanismo subyacente de sus efectos protectores contra el IM aún no se conocen. Se incluyeron un total de 60 ratas macho Sprague Dawley saludables. En el grupo control se incluyeron ratas que fueron sometidas a una cirugía utilizada para inducir el IM, pero sin ligar la arteria coronaria descendente anterior izquierda (ACDAI) y recibieron suero fisiológico normal (0,5 ml) como vehículo; el segundo grupo modelo de IM fueron ratas con ligadura de ACDAI y recibieron suero fisiológico normal (0,5 ml); el tercer grupo estuvo formado por ratas con IM + grelina, expuestas a la cirugía para inducir IM pero luego recibieron grelina (100 m/kg, oralmente, 2x/día). Al final del experimento, 21 días después del infarto de miocardio, los animales fueron sacrificados y procesados para el estudio ultraestructural. Nuestro experimento mostró que la grelina inhibe la apoptosis de los cardiomiocitos. La administración concomitante de grelina en ratas con IM parece indicar una protección considerable de los tejidos atriales. Además, el estudio reveló que el sarcoplasma estaba ocupado por miofibrillas normales con estriaciones claras y otras con una alteración menor. Se encontró una distribución normal de los gránulos del factor natriurético atrial (FNA) e integridad mitocondrial bien conservada (crestas conservadas, tamaño y forma normales), disposición de la cromatina del núcleo y patrón estriado de bandas claras (Z y H) en comparación con el grupo IM. También se observó un disco intercalado intacto con una clara identificación de la adherencia de la fascia completamente formada y desmosomas con una reconstrucción de la unión gap (nexo). Los miocitos atriales, después de un infarto de miocardio, a menudo se asocian con insuficiencia cardíaca posterior, que podría conducir a un desenlace fatal. En un modelo de rata de infarto de miocardio experimental, la administración de grelina periférica atenuó la disfunción de miocitos, con conservación del desmosoma, adherencia y unión de la brecha del disco intercalado y una distribución normal de los los gránulos de FNA.

Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction.

This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 µg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes.

Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling.

The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i.p., daily). All treatments were administered for 3 weeks. Administration of ghrelin to MI rats improved left ventricle (LV) architecture and restored cardiac contraction. In remote non-infarcted areas of MI rats, ghrelin reduced cardiac inflammation and lipid peroxidation and enhanced antioxidant enzymatic activity. In addition, independent of the growth factor/insulin growth factor-1 (GF/IGF-1) axis, ghrelin significantly increased the phosphorylation of JAK2 and Tyr702 and Ser727 residues of STAT3 and inhibited the phosphorylation of JAK1 and Tyr701 and Ser727 residues of STAT1, simultaneously increasing the expression of BCL-2 and decreasing in the expression of BAX, cleaved CASP3, and FAS. This effect coincided with decreased expression of SOCS3. All these beneficial effects of ghrelin, except its inhibitory action on IL-6 expression, were partially and significantly abolished by the co-administration of AG490. In conclusion, the cardioprotective effect of ghrelin against MI-induced LV injury is exerted via activation of JAK2/STAT3 signaling and inhibition of STAT1 signaling. These effects were independent of the GF/IGF-1 axis and could be partially mediated via inhibition of cardiac IL-6.

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

The association between physical activity and overweight and obesity in a population of children at high and low altitudes in Southwestern Saudi Arabia.

OBJECTIVE: To assess the relationship between overweight and obesity and physical activity in Saudi children born and permanently domiciled at high and low altitudes in Southwestern Saudi Arabia. SUBJECTS AND METHODS: A cross-sectional study of 145 healthy Saudi children aged 10-15 years who were born and lived permanently at high altitude (3000-3100 m) and 154 healthy Saudi children of comparable age who were born and lived permanently at a relatively low altitude (500 m) was conducted. For each subject selected, body weight and body height were measured using an Avery beam weighing scale and a stadiometer, respectively. Body mass index (BMI) was calculated using the equation BMI = (weight [kg]/height [m(2)]). Physical activity scores were determined using International Physical Activity Questionnaire-Short Form-A. Resting radial pulse rate (beat/minutes) was determined clinically. RESULTS: Physical activity was significantly and inversely associated with overweight and obesity in boys at both high (χ(2) = 15.8, P< 0.001) and low (χ(2) = 14.7, P< 0.001) altitudes, but there was no clear trend for girls at either altitude. The lack of association between physical activity and overweight and obesity in girls was attributed to the low and homogeneous level of physical activity. CONCLUSION: Physical activity should be encouraged as a strategy for weight reduction in the overweight and the obese and the prevention of overweight and obesity in Saudi children at high and low altitudes.

Increased systemic low-grade inflammation in high altitude native rats mediated by adrenergic receptors.

OBJECTIVE: To compare the serum levels of inflammatory mediators in high altitude (HA) native rats, and to search for the possible underlying mechanism(s). METHODS: The study was carried out between January and April 2013. Fifty male rats from the same genetic pool were bred at either a HA or low altitude (LA) area. The study was carried out in 2 stages. In the first stage, serum levels of inflammatory markers, adhesive molecules, lipid profiles, catecholamines, magnesium (Mg+2), and lipid peroxidation were compared between theses 2 groups. In the second stages, inflammatory response and lipid peroxidation were analyzed in HA native rats after treatment with either alpha (Prazosin) or beta (propranolol) adrenergic blockage. RESULTS: The HA native rats showed significant increases in the serum levels of inflammatory cytokines, lipid profiles, as well as a significant increase in the urinary norepinephrine with a concomitant decrease in the serum levels of Mg+2 and increased lipid peroxidation. Blockage of the beta and alpha adrenergic receptors of the HA rats caused partial or complete decreases in both inflammatory and oxidative stress mediators. CONCLUSION: Living under HA conditions results in an increased systemic inflammatory reaction; an effect that is mediated through the sympathetic nervous system mainly via alpha-adrenergic receptors and could be attributed to low Mg+2 levels.

Preventive roles of swimming exercise and pioglitazone treatment on hepatic dysfunction in a rat model of metabolic syndrome.

Pioglitazone (Pio) and swimming exercise (SE) are insulin sensitisers. This investigation was suggested because of the significant side effects associated with Pio treatment in metabolic syndrome (MetS). This study was, therefore, designed to investigate the preventive role of Pio treatment and SE in terms of efficiency and pathological changes in MetS in a rat model. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) control group (C), (ii) exercised control group (C+E), (iii) Pio-treated control group (C+Pio), (iv) group with MetS, (v) group with MetS treated with Pio (MetS+Pio), and (vi) exercised MetS group (MetS+E). Systolic blood pressure and heart rate were measured at the end of the experiments (16 weeks). Retro-orbital blood samples were used to determine the serum levels of glucose, insulin, lipids, gamma glutamyl transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A, and adiponectin. Semiquantitative reverse transcriptase - PCR insulin gene expression assays and hepatic histopathological examination were conducted. Swimming exercise significantly improved all of the aforementioned parameters, more so than the Pio treatment. In particular, the serum hepatic enzyme levels and hepatic histopathological changes were improved compared with the MetS group. These results suggested that swimming exercise might be an alternative physiological preventive tool against hepatic dysfunction to avoid the side effects associated with Pio treatment, and this could be demonstrated in a rat model of metabolic syndrome.

Role of vitamins E and C in mitigating hypoxia- and exhaustive exercise-induced aberrant stem cell factor expression and impaired reproductive function in male Wistar rats.

OBJECTIVE: To evaluate and compare the potential role of vitamins E and C in protecting against acute swimming induced reproductive function damage at different altitudes. METHODS: The study was carried between October and November 2010. A total of 36 adult male Wistar rats weighing 250+/-5 g, and aged 8 weeks were used in this study, which was carried at the Physiology laboratory of King Khalid University in Abha City (high altitude area [HA]), and at the College of Science, King Saud University in Riyadh city (low altitude area [LA]), Kingdom of Saudi Arabia. The rats of each area were divided into 3 groups (n=6 each): control, acute exercise stress, and vitamins E and C pretreated stress. At the end of the study, oxidative stress, reproductive function, histopathology, and expression of stem cell factor (CSF) were examined in all rats. RESULTS: Living under HA conditions decreased expression of SCF, sperm count, and serum levels of reproductive hormones, and significantly increased testicle tissue oxidative stress and lipid peroxidation. Exhaustive exercise-induced stress at both altitudes resulted in similar results with more deteriorating effects in rats of HA compared with LA. Supplementation of vitamins E and C prior to stress induction at both altitudes prevented all these structural and functional aberrations from happening. CONCLUSION: High altitude or strenuous exercise, or both, may impair male reproductive function, while vitamins E and C in combination potentially mitigate these adverse effects.

Chronic exposure of rats to native high altitude increases in blood pressure via activation of the renin-angiotensin-aldosterone system.

OBJECTIVE: To study the effect of chronic exposure to native high altitude (HA) on blood pressure, and to investigate the underlying mechanism of action. METHODS: This study was carried out between February and April 2011. A total of 20 male rats were divided into 2 groups (n=10 rats). The low altitude (LA) group were rats born and lived in an LA environment at King Saud University, College of Pharmacy, Riyadh, Kingdom of Saudi Arabia (KSA), and the HA group were rats born in the same LA area, then acclimatized to HA area in Physiology Department, King Khalid University, College of Medicine, Abha, KSA for 90 days. At the end of day 90, hematocrit, plasma renin activity, aldosterone, norepinephrine and vasopressin levels were determined in both groups. Invasive arterial blood pressure was also measured, and fractional excretion of sodium (FENa), and potassium (FEK) were calculated. The quantitative real time-polymerase chain reaction of renin was carried out in the kidneys of both rat groups. RESULTS: When compared to LA native rats, HA rats exhibited a significant increase in systolic and diastolic blood pressure with a significant increase in renin plasma activity as well as an increase in the levels of aldosterone, norepinephrine, and vasopressin. Furthermore, HA rats showed a significant increase in renin expression in their kidneys, as well as decreased FENa. CONCLUSION: Data shows that prolonged exposure to HA results in elevated blood pressure precipitated by the activation of the renin-angiotensin-aldosterone system.

Acute oral administration of Khat (Catha edulis) aqueous extract elevates blood pressure and prolongs QT and QTC intervals in Wistar albino rats.

OBJECTIVE: To investigate the effect of Khat (Catha edulis) acute administration on blood pressure (BP) and electrocardiogram (ECG) in vivo. METHODS: This study was performed between January and February 2009 at the Physiology Laboratory, Medical College of King Khalid University, Abha, Kingdom of Saudi Arabia. Two groups of Wistar rats (n=10), weighing 190-200 g were divided into control group and Khat treated group. Throughout the study, arterial BP and ECG were recorded for 60 consecutive minutes. The data were collected and analyzed by Power Lab Data Acquisition System every 10 minutes, and were compared within and between the groups. RESULTS: Oral administration of Khat resulted in significant time dependent increases in both systolic and diastolic BP with a maximum increase at minute 60 after extract administration (systolic BP--34.1%; and diastolic BP--46.2%). Heart rate was significantly increased at all minutes of the study with a maximum increase occurring at minute 40 (12.8%). There was a significant decrease in PR interval through the experiment, and the maximum decrease was observed at minute 40 (-15.2%). However, QT and QTc started to widen 20 minutes after extract administration with a maximum prolongation in both intervals to occur at minute 40 (QT--11.6%; QTc--9.1%). CONCLUSION: These newly reported changes in the ECG of rats after Khat administration should be a warning regarding the cardiac hazards of Khat chewing.

Potential roles for vitamins E and C in combination in modulating exhaustive swimming and high altitude-associated lung injury in rats.

OBJECTIVE: To evaluate and compare the potential role of vitamins E and C in protecting against acute swimming induced lung damage at different altitudes. METHODS: The study was carried out between January and March 2011. Eighteen male rats were bred and reared at either high altitude in Abha city or low altitude in Riyadh city, KSA. The rats were divided into 3 groups: 1) non-stress control, 2) forced swimming stressed, and 3) vitamin E and C pretreated stressed. At the end of the procedure, lung tissue levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were determined. RESULTS: In control rats, the baseline levels of TBARS were significantly increased and the baseline levels of both GSH and SOD were significantly decreased in the lungs of animals at high altitude compared with those at low altitude. Acute forced swimming resulted a significant increase in TBARS levels and a significant decrease in activities of SOD and CAT in the lungs in both altitude areas, and resulted in a significant decrease in GSH levels at high altitude rats only as compared with the resting state. Supplementation of vitamins E and C in combination effectively ameliorated all the parameters measured at both altitudes. CONCLUSION: Our novel observations suggest that supplementation of vitamins E and C could be beneficial against exhaustive swimming- and high altitude-associated lung injury.

Acute exposure to Catha edulis depresses contractility and induces myocardial infarction in spontaneously contracting, isolated rabbit's heart.

Khat chewing is a recreational habit known to pose major socio-economic and medical problems in countries of Southern Arabia and the Horn of Africa. Among other adverse health effects, khat chewing has been associated with an increased risk of myocardial infarction (MI) in heavy consumers. This study was carried out to examine the direct effects of Catha edulis extract on contractility of spontaneously contracting, isolated rabbit heart and to investigate its mechanism of action. Isolated six rabbit's hearts attached to a Langendorff apparatus were perfused with extract at a constant flow rate and continuously bubbled with a 95% O2/5% CO2 gas mixture. Each heart served as its own control, as responses were recorded before and after administration of C. edulis extract. Varying concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate, their effects recorded and effluent fluid collected for assay of cardiac enzymes. Histological examination of the cardiac tissue was performed at the end of perfusion with 250 mg/ml extract. This study revealed that acute exposure to C. edulis extract exerted negative inotropic and chronotropic effects on isolated hearts. The extract also had a vasoconstrictor effect on coronary vessels, independent of α1 adrenergic receptor stimulation. Histological examination of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of histological changes unique to myocardial infarction, a finding consistent with observed increased levels of cardiac enzymes in perfusates. Thus, we have demonstrated experimentally a direct cardiac depressant- and MI inducing effects of C. edulis extract. These results are consistent with the earlier reported deleterious effects of khat on cardiovascular function among khat chewers.

Gastroprotective effects of aqueous extract of Chamomilla recutita against ethanol-induced gastric ulcers.

OBJECTIVE: To investigate the gastroprotective effects of an orally administered aqueous extract of Chamomilla recutita (ACE) against ethanol-induced gastric ulcers in male Wistar rats. METHODS: This study was performed during January and February 2009, in the Research Labs in the Department of Physiology at the Medical School, King Khalid University, Abha, Kingdom of Saudi Arabia. Sixty white albino rats were divided into 5 groups. Group 1 (control group) was treated with deionized water for 28 days; animals in group 2 to group 5 received zero, 0.5, 1, or 2 gm/kg ACE for 27 days. Stomach ulcerations were induced by orally administering a single dose of 70% ethanol on day 28. Lesions in the gastric mucosa were examined macroscopically to calculate the ulcer index (UI) and estimated glutathione (GSH) for each animal. RESULTS: Compared to non-ACE treated rats, the UI decreased significantly in a dose-dependent manner in treated animals. Furthermore, GSH levels fell significantly after ethanol treatment; this decrease was prevented by ACE treatment. However, daily treatment of rats with the maximum ACE dose actually led to an increase in GSH levels. Histological examination revealed that ACE treatment alleviated, or completely resolved ethanol-induced degenerative alterations, including disorganization of cell nuclei and gland morphology with erosion in the gastric mucosa and interrupted muscularis mucosa. CONCLUSION: This study provides evidence for the regulation of ACE-mediated gastroprotection against ethanol-induced ulceration by GSH.

In vivo acute effects of orally administered hydro-ethanol extract of Catha edulis on blood glucose levels in normal, glucose-fed hyperglycemic, and alloxan-induced diabetic rats.

OBJECTIVE: To investigate the blood glucose lowering effect of khat (Catha edulis) extract in normal, glucose-loaded, and alloxan diabetic rats. METHODS: Three experimental protocols were used in this study. In each of the first 2 protocols, 3 groups of rats (6 rats per group) were used as control group (NS), Catha edulis (CE) treated, and glibenclamide treated groups. This study was carried out at the Physiological Laboratory of the Medical School of King Khalid University, Abha, Saudi Arabia between October and November, 2009. Normal rats were used in the first protocol while alloxan diabetic rats were used in the second protocol. Blood glucose levels were measured in all 3 groups after single dose injections of saline, CE or glibenclamide. In the third protocol, another 6 groups of rats (6 rats per group) were prepared as in the first 2 protocols and oral glucose tolerance test (OGTT) was performed on each rat after oral administration of glucose (1.5 g/kg). RESULTS: Oral administration of a hydro-ethanol extract of CE caused no statistically significant change in blood glucose levels in normal rats with or without glucose loading. There were slight, non significant increases in blood glucose levels of extract-treated diabetic rats, with and without glucose loading, as compared to the corresponding untreated rats. CONCLUSION: Oral administration of CE extract does not exert a hypoglycemic effect in normal, glucose-loaded, and diabetic rats.

Cardiac adaptive responses after hypoxia in an experimental model.

The role of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in mediating hypoxic preconditioning under the acute intermittent hypoxic condition (AIH) was investigated in this study. Male Wistar rats were randomly assigned and kept in normoxic conditions, (Nx) or in AIH conditions and subjected to brief cycles hypoxia/reoxygenation. Hearts were isolated, perfused, and subjected to in vitro global ischemia followed by reperfusion. During and at the end of reperfusion, left ventricular developed pressure (LVDP); LV end diastolic pressure (LVEDP); rate pressure product (RPP); peak left ventricular pressure rise (DeltaP/Deltat (max) ) and heart rate (HR) were measured. Hearts subjected to AIH displayed a significant higher LVDP (P < .001), RPP (P < .001), and DeltaP/Deltat ( max) (P < .001). Expression of VEGF and EPO were significantly increased at 3, 8, and 24 hours after AIH. Hypoxic training could provide a new approach to enhance endogenous cardioprotective mechanisms.

The prevalence of malnutrition among high and low altitude preschool children of southwestern Saudi Arabia.

OBJECTIVE: To assess the current status of protein energy malnutrition (PEM) in the high and low altitude preschool children aged 12-71 months. METHODS: A cross-sectional study conducted during the year of 2003 and involved 572 and 469 preschool children of Southwestern Saudi Arabia born and living permanently at high and low altitude areas. Anthropometric measurements were carried out to assess the prevalence of PEM using 3 indicators such as underweight, wasting and stunting following World Health Organization standards. Prevalence differences were examined by age, gender, altitude, and parental socioeconomic status. RESULTS: The prevalence of the 3 types of PEM was significantly higher at low altitude than at high altitude and significantly higher among children born to illiterate than to educated parents. Older children were more underweight and stunted than younger children and underweight and wasting were significantly more common in boys than girls. Annual family income per person was negatively and significantly associated with underweight and stunting, but not with wasting. Multivariate analysis showed that after controlling for all sociobiological factors, low altitude remained a strong risk factor. CONCLUSION: The difference in PEM between high and low altitude preschool children could be related to the milder environmental conditions at high altitude and the higher incidence of tropical infections in lowland children. Future studies are required to verify these speculations, and to establish programs to control and prevent PEM in preschool children at low altitude.

The effect of long-term use of computer mouse devices on median nerve entrapment.

OBJECTIVE: To assess the effect of long-term use of computer mouse devices on the median nerves. METHODS: A cross-section prospective study conducted during the year 2004 involved 41 male secretaries employed in the Health Colleges of King Khalid University in Abha, Kingdom of Saudi Arabia. A questionnaire describing sociodemographic and computer use was completed. The electrophysiological study included measurements of motor latencies, motor conduction velocities, and amplitudes of compound muscle action potential of the right median nerve and compared these with those of the left median nerve (control). All of our subjects were right handed. Terminal latency index (TLI) was calculated for each nerve tested. Entrapment neuropathy of the median nerve at the wrist was defined as TLI <0.30. RESULTS: The mean TLI of the median nerve in the right hand was significantly lower than that in the left hand. Eight of the 23 asymptomatic participants (34.8%), 6 of the 12 who reported hand discomfort (50%), and all the 6 participants who met clinical criteria for carpal tunnel syndrome showed electrophysiological evidence suggestive of right median nerve entrapment neuropathy at the wrist. Test of association showed a negative and significant correlation between TLI of the right median nerve and weekly hours mouse device use while no significant correlation was found between TLI in the same hand and weekly hours keyboard use. CONCLUSION: Frequent computer mouse device users are at high risk of developing median nerve entrapment neuropathy at the wrist.