Taurine prevents high-fat diet-induced-hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element-binding proteins and activation of AMPK.

This study investigated if the protective effect of taurine against high fat diet-induced hepatic steatosis involves modulating the hepatic activity of 5' AMP-activated protein kinase (AMPK) and levels/activity of the sterol regulatory element-binding proteins-1/2 (SREBP1/2). Rats were divided into four groups (n = 12/group) as (a) STD, fed standard diet (3.85 kcal/g); (b) STD + taurine (500 mg/kg); (c) HFD, fed HFD (4.73 kcal/g); and (d) HFD + taurine. All treatments were conducted for 12 weeks. Independent of food intake or modulating glucose or insulin levels, taurine administration to STD and HFD-fed rats significantly lowered weekly weight gain and the accumulation of the retroperitoneal, visceral and subcutaneous fats. In both groups, taurine also reduced serum and hepatic levels of triglycerides and cholesterol and reduced hepatic mRNA and protein levels of fatty acid synthase (FAS), acetyl CoA carboxylase-1 (ACC-1), HMG-CoA-reductase and HMG-CoA synthetase. In control rats only, taurine reduced hepatic levels of mature forms of sterol regulatory element-binding proteins (SREBP)-1/2. In HFD-fed rats, taurine reduced SREBP-1/2 precursor and mature forms in the livers of HFD-fed rats. Besides, taurine significantly increased levels of glutathione (GSH), the activity of superoxide dismutase (SOD), and the activity of AMPK and its downstream ß-oxidation genes including peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase (CPT-1) in the livers of both the control and HFD-fed rats. In conclusion, taurine protects against HFD-induced hepatic steatosis stimulating antioxidant levels, and concomitant stimulating hepatic ß-oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP-1.

Two episodes of remote ischemia preconditioning improve motor and sensory function of hind limbs after spinal cord ischemic injury.

Objectives: To investigate the effect of one and two remote ischemia preconditioning episodes (1-RIPC or 2-RIPC, respectively) on neuro-protection after spinal cord ischemic injury (SCI) in rats. Design: Experimental animal study. Setting: College of Medicine, King Khalid University, Abha, KSA. Interventions: Male rats (n = 10/group) were divided into control, sham, SCIRI, 1-RIPC + SCIRI, and 2-RIPC + SCIRI. SCI was induced by aortic ligation for 45 min and each RIPC episode was induced by 3 cycles of 10 min ischemia/10 min perfusion. The two preconditioning procedures were separated by 24 h. Outcome measures: after 48 h of RIPC procedure, Tarlov's test, withdrawal from the painful stimulus and placing/stepping reflex (SPR) were used to evaluate the hind limbs neurological function. SC homogenates were used to measure various biochemical parameters. Results: Motor and sensory function of hind limbs were significantly improved and levels of MDA, AOPPs, PGE2, TNF-α, and IL-6, as well as the activity of SOD, was significantly decreased in SC tissue in either 1 or 2 episodes of RIPC intervention. Concomitantly, levels of total nitrate/nitrite and eNOS activity were significantly increased in both groups. Interestingly, except for activity of SOD, eNOS and levels of nitrate/nitrite, the improvements in all neurological biochemical endpoint were more profound in 2-RIPC + SCIRI compared with 1-RIPC + SCIRI. Conclusion: applying two preconditioning episodes of 3 cycles of 10 min ischemia/10 min perfusion, separated by 24 h, boost the neuro-protection effect of RIPC maneuver in rats after ischemic induced SCI in rats.

Hemostatic effect of acylated ghrelin in control and sleeve gastrectomy-induced rats: mechanisms of action.

This study investigated the effect of acylated ghrelin (AG) deficiency after sleeve gastrectomy (SG) or chronic administration in control and SG-indiuced rats on platelet function, coagulation, and fibrinolysis. Administration of AG (100 µg/kg, subcutaneously) to control or SG rats significantly inhibited platelets aggregation and lowered levels of Von-Willebrand factor (vWF), fibrinogen, and thromboxane B2. Concomitantly, it decreased circulatory levels and aortic expression levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and increased the aortic expression of the endothelial nitric oxidase (eNOS). However, AG inhibited angiotensin-II (ANGII)-induced upregulation of tissue factor pathway inhibitor (TPAI) and TF and increased activity of TF and increases eNOS expression in cultured endothelial cells, an effect that was abolished by the addition of D-[lys3]-GHRP-6, a selective AG receptor (GHSR-1a) blocker or L-Name, a potent eNOS inhibitor. In conclusion, AG has an anti-platelet, anti-coagulant, and fibrinolytic roles mediated through GHSR-1a to enhance nitric oxide synthesis.

Protective effect of combined melatonin and alpha-tocopherol administration in spinal cord ischemia-reperfusion injury in rat / Efecto protector de la administración combinada de melatonina y alfa-tocoferol en la lesión por isquemia-reperfusión de la médula espinal en ratas

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.

El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.

Impact of High Altitude on Maternal Serum Leptin Level and its Correlation With Oxidative Stress and Endothelial Inflammatory Markers in Preeclamptic Women.

Involvement of leptin in the pathogensis of preeclampsia (PE) is still a controversy subject. Several researches reported the changes in serum leptin in high altitude (HA) residents. The aim of the present work was to investigate the impact of oxidative stress (OS) induced by HA residence on maternal serum leptin in PE and if there was a significant correlation between the serum leptin with either OS or endothelial inflammatory markers. One hundred fifty eight pregnant women were included in this study, divided into: low altitude normal pregnancies (NL), HA normal pregnancies (NH), low altitude preeclamptic (PL), and HA preeclamptic (PH) who presented to the obstetrics and gynecology outpatient clinic in both Muhayl (500 m over sea level) and Abha General Hospitals (all of them resident at Alsoda district with the average altitude 2700 m over sea level). Serum leptin, superoxide dismutase (SOD) activity, malondialdehyde (MDA), plasma nitrite/nitrate (NOx), serum tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), blood urea nitrogen (BUN) and creatinine were determined. Both NH and PL groups showed significant increases in leptin (P < 0.01), SOD (P < 0.01), MDA (P < 0.001), NOx (P < 0.001), TNF-α (P < 0.001) and IL-6 (P < 0.001) compared with the NL group without any significant changes between both groups. The PH group showed significant accentuation of the previously measured parameters (P < 0.001 for all) compared with all other groups (NL, NH and PL groups). We can conclude that the combination of PE and HA residence resulted in significantly elevated maternal serum leptin suggesting involvement of leptin in the pathogenesis of PE accentuated by HA residence.