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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), (ill) 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. Key words: metabolic syndrome, pioglitazone, swimming exercise, adiponectin, semiquantitative RT-PCR for insulin gene expression. Resume : Le pioglitazone (Pio) et la natation sont des sensibilisateurs a l'insuline. Cette recherche a ete suggeree par les effets secondaires significatifs associes au traitement du syndrome metabolique par le Pio. Cette etude a ete concue afin d'examiner le role preventif du traitement au Pio et de la natation en termes d'efficacite et de changements pathologiques dans un modele de syndrome metabolique (SM) chez le rat. Soixante rats Sprague-Dawley males ont ete repartis en 6 groupes egaux : (i) controle (C), (ii) controle et exercice (CE), (iii) controle et traitement au Pio (C+Pio), (iv) SM, (v) SM+Pio et (vi) SM+E. A la fin du protocole experimental (16 semaines), la pression sanguine systolique et le rythme cardiaque ont ete determines. Les echantillons sanguins retro-orbitaux ont ete utilises afin de mesurer le glucose, l'insuline, le lipogramme, la gamma glutamyl transferase, l'alanine transaminase, l'aspartate transaminase, la phosphatase alcaline, la fetuine A, et l'adiponectine du serum. Des dosages de l'expression genique de l'insuline par RT-PCR semi-quantitative et un examen histopathologique du foie ont ete realises. La natation ameliorait significativement les parametres mentionnes plus haut et ce, plus efficacement que le traitement au Pio, notamment le niveau serique des enzymes hepatiques et les changements histopathologiques hepatiques comparativement au groupe SM. Ces resultats ont suggere que la natation pouvait constituer un outil physiologique alternatif de prevention de la dysfonction hepatique lors du syndrome metabolique, lors d'une etude visant a eviter les effets secondaires associes au traitement au Pio. [Traduit par la Redaction] Mots-cles: syndrome metabolique, pioglitazone, natation, adiponectine, RT-PCR semi-quantitative de l'expression genique d'insuline., Introduction Metabolic syndrome (MetS) is a major global health problem associated with obesity that affects different organs, especially the key metabolic organs such as the liver (Grundy 2008). Nonalcoholic fatty [...]

Context: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia. Objective: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats. Materials and methods: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups (n=8 rats/group) as control, controlþEA, controlþEAþCC an AMPK inhibitor), T1DM, T1DMþEA, and T1DMþEAþCC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily. Results: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-a (62%), and IL-6 (57.2%) and the nuclear activity of NF-jB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARa (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC. Discussion and conclusions: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine. [ABSTRACT FROM AUTHOR]

This study evaluated the protective effect of resolvin D1 (RVD1) against cadmium chloride (CdCl2)‐induced hippocampal damage and memory loss in rats and investigated if such protection is mediated by modulating the PTEN/PI3K/Akt/mTOR pathway. Adult male Wistar rats (n = 18/group) were divided as control, control + RVD1, CdCl2, CdCl2 + RVD1 and CdCl2 + RVD1 + bpV(pic), a PTEN inhibitor. All treatments were conducted for 4 weeks. Resolvin D1 improved the memory function as measured by Morris water maze (MWM), preserved the structure of CA1 area of the hippocampus, and increased hippocampal levels of RVD1 in the CdCl2‐treated rats. Resolvin D1 also suppressed the generation of reactive oxygen species (ROS), tumour necrosis factor‐α and interleukine‐6 (IL‐6), inhibited nuclear factor κB (NF‐κB) p65, stimulated levels of glutathione (GSH), manganese superoxide dismutase (MnSOD), and Bcl2 but reduced the expression of Bax and cleaved caspase 3 in hippocampi of CdCl2‐treated rats. Concomitantly, it stimulated levels and activity of PTEN and reduced the phosphorylation (activation) of PI3K, Akt and mTOR in hippocampi of CdCl2‐treated rats. In conclusion, RVD1 attenuates CdCl2‐induced memory loss and hippocampal damage in rats mainly by activating PTEN‐induced suppression of PI3K/Akt/mTOR, an effect that seems secondary to its' anti‐oxidant and anti‐inflammatory potential. [ABSTRACT FROM AUTHOR]

This study investigated if cadmium chloride (CdCl2)‐induced hepatic steatosis and fibrosis and the protective effect of quercetin (QUR) are mediated modulating the activity of miR‐21, a known hepatic lipogenic and fibrotic miRNA. Male rats (n = 8/group) were divided as control, control + QUR (50 mg/kg; orally), CdCl2 (10 moml/L; drinking water), CdCl2 + miR‐21 antagomir (inhibitor) (16 mg/kg/first 3 days), and CdCl2 + QUR (50 mg/kg). Treatments were conducted for 20 weeks, daily. All treatments showed no effect on fasting glucose and insulin levels. Administration of either miR‐21 or QUR prevented CdCl2‐induced hepatic damage, as well as lipid droplets and collagen deposition. They also reduced serum levels of ALT and AST and decreased serum and hepatic levels of total cholesterol, triglycerides, and low‐density lipoproteins in CdCl2‐treated rats. Concomitantly, they reduced hepatic levels of reactive oxygen species, malondialdehyde, interleukin‐6, and tumor necrosis factor‐α, suppressed the activation of NF‐kb P65, and increased hepatic levels of nuclear factor erythroid 2‐related factor 2 (Nrf2), glutathione (GSH), and superoxide dismutase (SOD). These effects were associated with reduced expression of SREBP1, TGF‐β1, Smad3, and collagen1 A and increased expression of PPARα, CPT1, and smad7. Interestingly, QUR significantly lowered levels of miR‐21 and increased the protein levels and activity of Nrf2, as well as levels of GSH and SOD in the livers of both the control and CdCl2‐treated rats. Of note, levels of Nrf2 were negatively correlated with the transcription of miR‐21. In conclusion: QUR prevents CdCl2‐induced hepatic steatosis and fibrosis mainly through attenuating its ability to upregulate miR‐21, at least, by upregulation of Nrf2. [ABSTRACT FROM AUTHOR]

Context:Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders. Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats. Materials and methods: Wistar Male rats (180–220 g) were divided (n = 10/group) as control fed a standard diet (STD), STD + C. aronia (200 mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20 mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8 weeks, and all other treatments were administered for 4 weeks. Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90 ± 5 vs. 160 ± 11.3 µm) and adventitia (54.3 ± 3.8 vs. 93.6 ± 9.4 µm). It also lowered protein levels of TNF-α (0.51 ± 0.15 and 0.15 ± 0.16 vs. 0.1 ± 0.09%) and IL-6 (0.52 ± 0.19 vs. 1.0 ± 0.2%) in their aorta or serum (5.9 ± 0.91 vs. 12.98 ± 1.3 ng/mL and 78.1 ± 6.7 vs. 439 ± 78 pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4 ± 4.0 vs. 40.7 µM) and activity of SOD (5.7 ± 0.7 vs. 2.9 ± 0.6 U/mg) and decreased serum levels of ox-LDL-c (566.7 ± 46 vs. 1817 ± 147 ng/mL). Such effects were more profound than all other treatments. Conclusions:C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended. [ABSTRACT FROM AUTHOR]

This study investigates the effect of chronic consumption of a high‐fat diet rich in corn oil (CO‐HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)‐induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet (STD) (3.82 kcal/g, 9.4% fat), CO‐HFD (5.4 kcal/g, 40% fat), T1DM fed STD, and T1DM + CO‐HFD. CO‐HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase‐3, and ANF and decreased levels of Bcl‐2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO‐HFD. In conclusion, chronic consumption of CO‐HFD by T1DM‐induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria‐mediated cell death. [ABSTRACT FROM AUTHOR]

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg−1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1β, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi. [ABSTRACT FROM AUTHOR]

This study investigated if calcineurin/nuclear factor of activated T cells (NFAT) axis mediates the cardiac apoptosis in rats with type 1 diabetes mellitus (T1DM)-induced rats or administered chronically high-fat diet rich in corn oil (CO-HFD). Also, it investigated the impact of chronic administration of CO-HFD on Fas/Fas ligand (Fas/FasL)-induced apoptosis in the hearts of T1DM-induced rats. Adult male Wistar rats (140-160 g) were classified as control: (10% fat) CO-HFD: (40% fat), T1DM, and T1DM + CO-HFD (n=20/each). In vitro, cardiomyocytes were cultured in either low glucose (LG) or high glucose (HG) media in the presence or absence of linoleic acid (LA) and other inhibitors. Compared to the control, increased reactive oxygen species (ROS), protein levels of cytochrome C, cleaved caspase-8 and caspase-3, myocardial damage and impeded left ventricular (LV) function were observed in the hearts of all treated groups and maximally in T1DM + CO-HFD-treated rats. mRNA of all NFAT members (NFAT1-4) were not affected by any treatment. CO-HFD or LA significantly up-regulated Fas levels in both LVs and cultured cardiomyocytes in a ROS dependent mechanism and independent of modulating intracellular Ca2+ levels or calcineurin activity. T1DM or hyperglycemia significant up-regulated mRNA and protein levels of Fas and FasL by activating Ca2+/calcineurin/NFAT-4 axis. Furthermore, Fas/FasL cell death induced by recombinant FasL (rFasL) or HG media was enhanced by pre-incubating the cells with LA. In conclusion, activation of the Ca2+/calcineurin/NFAT4 axis is indispensable for hyperglycemia-induced Fas/FasL cell death in the cardiomyocytes and CO-HFD sensitizes this by up-regulation of Fas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Increased oxidative stress and hormonal imbalance have been hypothesized to underlie infertility in obese animals. However, recent evidence suggests that Ghrelin and Stem Cell Factor (SCF) play an important role in fertility, in lean individuals. Therefore, this study aimed at investigating whether changes in the levels of Ghrelin and SCF in rat testes underlie semen abnormal parameters observed in obese rats, and secondly, whether endurance exercise or Orlistat can protect against changes in Ghrelin, SCF, and/or semen parameters in diet induced obese rats. Obesity was modelled in male Wistar rats using High Fat Diet (HFD) 12-week protocol. Eight week-old rats (n=40) were divided into four groups, namely, Group I: fed with a standard diet (12% of calories as fat); Group II: fed HFD (40% of calories as fat); Group III: fed the HFD with a concomitant dose of Orlistat (200 mg/kg); and Group IV: fed the HFD and underwent 30 min daily swimming exercise. The model was validated by measuring the levels of testosterone, FSH, LH, estradiol, leptin, triglycerides, total, HDL, and LDL cholesterol, and final change in body weight. Levels were consistent with published obesity models (see Results). As predicted, the HFD group had a 76.8% decrease in sperm count, 44.72% decrease in sperm motility, as well as 47.09% increase in abnormal sperm morphology. Unlike the control group, in the HFD group (i.e. obese rats) Ghrelin mRNA and protein were elevated, while SCF mRNA and protein were diminished in the testes. Furthermore, in the HFD group, SOD and GPx activities were significantly reduced, 48.5±5.8% (P=0.0012) and 45.6±4.6% (P=0.0019), respectively, while TBARS levels were significantly increased (112.7±8.9%, P≤0.0001). Finally, endurance exercise training and Orlistat administration in dividually and differentially protected semen parameters in obese rats. The mechanism includes, but is not limited to, normalizing the levels of Ghrelin, SCF, SOD, GPx and TBARS. In rat testes, diet induced obesity down regulates SCF expression, upregulates Ghrelin expression, and deteriorate oxidative stress levels, which are collectively detrimental to semen parameters. Exercise, and to a lesser extent Orlistat administration, protected effectively against this detrimental effect. [ABSTRACT FROM AUTHOR]

Objective: To determine the problems related to renal colic due to urinary stones during pregnancy, and the principles of management of those patients in our hospitals. Material and Methods: It is a retrospective analysis of a series of 21 cases of renal colic due to urinary stones during pregnancy from March 2008 to April 2010 at Prince Rashid Ben Al-Hassan Military Hospital, Jordan. Presenting symptoms, diagnostic studies and management of renal stone were evaluated. Results: There were 15,824 deliveries during this period in our study. 21 of them had renal colic due to urinary stones during pregnancy, with an overall incidence in this series of 0.13%. Most of them were in the third trimester of pregnancy followed by the second trimester and the least were in the first trimester. The most common complaints were lank pain (95.2 %), urinary symptoms (hematuria, dysuria and urgency) in 80.9%, nausea and vomiting in 14.3% and fever in 28.6 %. Spontaneous passing of stones was noted in 19 cases (90.5%) with conservative treatment. Two patients were unresponsive or relapsing after medical treatment and were treated surgically in the urological department by double J stents insertion, but no maternal or fetal loss was noted. Conclusion: The majority of cases of renal colic due to urinary stones during pregnancy can be safely managed conservatively. The commonest presenting symptoms in our study were lank pain, urinary symptoms (hematuria, dysuria and urgency), and early surgical intervention resulted in safe maternal and fetal outcome. [ABSTRACT FROM AUTHOR]

Objective: To identify and analyze the abnormal hysteroscopic findings in women with failed IVF, and their effect on pregnancy outcome. Methods and Materials: A simple, descriptive, non-randomized study of 245 patients was conducted at King Hussein medical center. All patients with failed IVF were referred to routine hysteroscopy in our hysteroscopic unit. The hysteroscopic finding was identified and recorded. The patients' ages ranged from 20 to 38 years and duration of infertility ranged from 5-10 years. Results: Uterine cavity was normal in 75% of the cases, while sixty one (25%) patients showed abnormal hysteroscopic findings of the cervical canal and uterine cavity (endometrium). The abnormal hysteroscopic findings seen were: intramural myoma: 26 cases, endometrial polyp: 19 cases, isthmic abnormalities were present in 8% (5 cases), endometrial hyperplasia in 3 cases, intrauterine adhesion (synechiae): 4 cases, and septate uterus in 4 cases. Conclusion: Patients with recurrent IVF embryo transfer failures should be reevaluated using hysteroscopy prior to further commencing IVF-embryo transfer cycles. Hysteroscopy is part of first-line exams in infertile woman regardless of age. [ABSTRACT FROM AUTHOR]

This study compared the effect of low‐fat diet (LFD) and high‐fat diet rich in corn oil (HFD‐CO) on left ventricular (LV) fibrosis in rats and examined their effect of angiotensin II (ANG II), JAK/STAT, and TGF‐1β/smad3 pathways. As compared to LFD which didn't affect any of the measured parameters, HFD‐CO‐induced type 2 diabetes phenotype and increased LV collagen synthesis. Mechanistically, it increased LV levels of ROS, ANG II, ACE, IL‐6, s‐IL‐6Rα, TGF‐β1, Smad‐3, and activities of JAK1/2 and STAT1/3. AG490, a JAK2 inhibitor, partially ameliorated these effect while Losartan, an AT1 inhibitor completely abolished collagen synthesis. However, with both treatments, levels of ANG II, IL‐6, and s‐IL‐6Rα, and activity of JAK1/STAT3 remained high, all of which were normalized by co‐administration of NAC or IL‐6 neutralizing antibody. In conclusion: HFD‐CO enhances LV collage synthesis by activation of JAK1/STAT3/ANG II/TGF‐1β/smad3 pathway. Practical applications: We report that chronic consumption of a high‐fat diet rich in corn oil (HFD‐CO) induces diabetes mellitus phenotype 2 associated with left ventricular (LV) cardiac fibrosis in rats. The findings of this study show that HFD‐CO, and through the increasing generation of ROS and IL‐6 levels and shedding, could activate LV JAK1/2‐STAT1/3  and  renin‐angiotensin system (RAS) signaling pathways, thus creating a positive feedback between the two which ultimately leads to activation of TGF‐1β/Smad3 fibrotic pathway. Herein, we also report a beneficial effect of the antioxidant, NAC, or IL‐6 neutralizing antibody in preventing such adverse effects of such HFD‐CO. However, this presents a warning message to the current sudden increase in idiopathic cardiac disorders, especially with the big shift in our diets toward n‐6 PUFA. [ABSTRACT FROM AUTHOR]

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 m/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. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects of testosterone (Test) deficiency and testosterone replacement therapy (TRT) on the development of non-alcoholic fatty liver disease (NAFLD) and associated peripheral insulin resistance (IR) in male rats and to illustrate the underlying mechanisms of action. Materials and methods: male Sprague Dawley rats were divided into 3 groups as follows: 1) sham-operated group (n = 11), 2) ORCD-induced group (n = 9) exposed to orchidectomy (ORCD), achieved by complete surgical removal of testicles, and 3) ORCD + Test treated group (n = 10) (11 ng/mL Test propionate, 3x/week, S.C.). Results: Data revealed significant increases in final body, liver, visceral and subcutaneous fats weights with significant increases in fasting plasma glucose and insulin levels and HOMA-IR. Additionally, ORCD rats had higher UAC for measured glucose levels and insulin levels during OGTT and higher AUC for measured glucose levels during ITT. Interesting, higher serum and hepatic levels of TGs and CHOL and higher serum levels of LDL were seen in ORCD-induced rats. Mechanistically, significant increases in mRNA levels of SREBP-1, SREBP-2, ACC-1, FAS, HMGCOAR and HMGCOAS with significant increases in protein levels of both precursor and mature SREBP-1 and SREBP-2, PPAR-α, p-PPAR-α, CPT-1 and UCP-2 and significant lower protein levels p-AMPK and p-ACC-1 were detected in livers of ORCD rats. Test administration to ORCD-induced rats significantly ameliorated all of the above mentioned biochemical endpoints and reversed the effect of ORCD on mRNA and protein levels of these targets. In conclusion , Test deficiency could be an independent risk factor for the development of NAFLD by upregulation of lipid synthesis and disturb fatty acids oxidation whereas Test therapy is a protective strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Stroke places a huge burden on the socioeconomic systems. Hemorrhagic stroke (HS) is the second most common type of stroke and the second leading cause of disability and death. The updated data on the prevalence of intracerebral hemorrhage (ICH) stroke and related physiological risk factors in Saudi Arabia were limited. The aim of this study was to identify the prevalence of ICH stroke and the related physiological risk factors. Methods This was a retrospective, hospital-based, and chart review study that utilized the BESTCare system at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Patients who attended the neurology department (inpatient/outpatient) between 2015 and 2020 were studied. The statistical tool JMP (JMP Inc., Cary, NC, USA) was used for data entry and analysis. Results Patient data (N = 1,870, 58.6 ± 13.87 years old) were screened for comorbidities, hypertension (66.1%), diabetes mellitus (DM) (57.7%), hyperlipidemia (28.4%), and history of an old stroke (22.3%). Ischemic stroke (IS) was more dominant than ICH stroke with ratios of 94.5% (n = 1767) versus 5.5% (n = 103), respectively. The prevalence of ICH stroke among the patients (n = 103) was 10.6%, 20.3%, 24.2%, and 28.1% in the age groups of <40, 41-50, 51-60, and 61-70 years old, respectively. There was a significant gender effect on the distribution of both IS and ICH (p = 0.003). ICH strokes were more prevalent in males than in females. Body mass index (BMI) has no significant effect on the prevalence of IS and ICH stroke (p = 0.081). ICH stroke was significantly associated with DM (p = 0.032), hypertension (p = 0.01), and hyperlipidemia (p = 0.002). Regression analyses show that only hypertension (positive association) and hyperlipidemia (negative association) were significantly associated with the incidence of ICH stroke. Conclusion IS was more prevalent than ICH stroke. ICH strokes were more prevalent in males than in females. Also, hypertension was the most common factor leading to ICH stroke, unlike hyperlipidemia, which was revealed to be protective against ICH stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Almuklass et al.)

Context: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia., Objective: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats., Materials and Methods: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups ( n  = 8 rats/group) as control, control + EA, control + EA + CC an AMPK inhibitor), T1DM, T1DM + EA, and T1DM + EA + CC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily., Results: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-α (62%), and IL-6 (57.2%) and the nuclear activity of NF-κB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARα (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC., Discussion and Conclusions: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Aim: Myocardial infarction (MI) due to sudden occlusion of a major coronary artery leads to a complex series of events that result in left ventricle (LV) impairment eventual heart failure. Therapeutic options are limited to reverse such trends post MI. The aim of this study was to compare the acute cardioprotective effects of the antioxidants, resveratrol (RES) and coenzyme Q10 (CoQ10), either individually or in combination, on infracts size, LV hemodynamics, inflammation and oxidative stress markers in rats with experimentally induced MI., Methods: Male Wistar rats were randomly divided into six groups: control without surgery, sham without occlusion, MI without antioxidants, RES pre-treated then MI (20 mg/kg, orally), CoQ10 then MI (20 mg/kg, intramuscular.), and combined RES and CoQ10 then MI with (each group n = 10). Pretreatment commenced 7 days prior to the permanent occlusion of the left anterior descending (LAD) coronary artery. Infarct area, hemodynamics, inflammation and oxidative stress markers were assessed 24 hours post-MI., Results: Compared to RES alone, CoQ10 pre-administration either by itself or in combination with RES, significantly reduced LV infarct area (57%), and normalized LV hemodynamic parameters like LVEDP (100%), LVSP (95.4%), LV +dp/dt and -dp/dt (102 and 73.1%, respectively). CoQ10 also decreased serum levels of brain natriuretic peptide (70%), and various circulating inflammatory markers like TNF-α (83.2%) and IL-6 (83.2%). Regarding oxidative stress, TBARS scores were lowered with a concurrent increase in both superoxide dismutase and glutathione peroxidase activities with CoQ10 alone or in combination with RES., Conclusion: Coenzyme Q10 protects against the acute sequelae of myocardial infarction. It profoundly reduced infarct area, inflammation and oxidative stress while normalizing LV hemodynamics post MI.

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.

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

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.

Thyroid hormones play an important role in cell growth and differentiation and regulation of oxygen consumption and thermogenesis. The effect of altitude and vitamin supplementation on thyroid hormone levels in animals or humans performing acute exhaustive exercise have not been investigated before. Therefore, we thought to test whether exhaustive exercise-induced stress with antioxidant supplementation was capable of modulating the level of thyroid hormones at different altitudes. Serum levels of T4 (Thyroxin), T3 (Triiodothyronine), and TSH (Thyroid Stimulating Hormone) were measured in rats (N=36) born and bred in low altitude (600 m above sea level) and high altitude (2200 m above sea level) following forced swimming with or without vitamins C and E (25 mg/kg) pre-treatments. Thyroid levels were significantly decreased in resting rats at high altitude compared to low altitude, and swimming exercise moderately increased T3 and TSH at both high and low altitudes, whereas T4 was markedly increased (62 %) at low altitude compared to a moderate high altitude increase (28 %). Co-administration of vitamins C and E augmented the observed forced swimming-induced thyroid release. However, the conversion of T4 to T3 was reduced in both altitude areas following swimming exercise and vitamin pre-treatment had no effect. We conclude that acute stress induced thyroidal hormones in rats, which was augmented by antioxidant drugs in both high and low altitude areas. These findings may play an important role in the human pathophysiology of thyroid gland at different altitudes.