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The present study investigated the possible renoprotective effect of direct renin inhibitor (aliskiren) on renal dysfunctions, as well as its underlying mechanisms in rat model of adenine-induced tubulointerstitial nephropathy. Forty male SpragueDawley rats were randomized into 4 groups; normal group, aliskiren group (normal rats received 10 mg/kg aliskiren), adenine group (animals received high-adenine diet for 4 weeks and saline for 12 weeks), and adenine + aliskiren group (animals received adenine for 4 weeks and aliskiren 10 mg/kg for 12 weeks). It was found that adenine caused significant decrease in body mass, Hb, HR, serum [Ca.sup.2+], eNOS and nrf2 expression, GSH, and catalase in kidney tissues with significant increase in arterial blood pressure (ABP), serum creatinine, BUN, plasma renin activity (PRA), [K.sup.+] and P, urinary albumin excretion (UAE), caspase-3, and MDA (lipid peroxidation marker) in kidney tissues compared to normal group (p < 0.05). Administration of aliskiren caused significant improvement in all studied parameters compared to adenine group (p < 0.05). We concluded that aliskiren has renoprotective effect against adenine-induced nephropathy. This might be due to inhibition of PRA, attenuation of oxidative stress, activation of Nrf2 and eNOS genes, and suppression of caspase-3. Key words: adenine, nephropathy, nrf2, caspase-3, eNOS, oxidative stress. L'etude presente a examine l'effet nephroprotecteur possible d'un inhibiteur direct de la renine (aliskiren) sur la dysfonction renale, de meme que ses mecanismes d'action sous-jacents dans un modele de nephropathie tubulo-interstitielle induite chez le rat par l'adenine. Quarante rats males Sprague-Dawley ont ete repartis de maniere aleatoire en quatre groupes : groupe normal, groupe aliskiren (rats normaux ayant recu 10 mg/kg d'aliskiren), groupe adenine (animaux nourris avec une diete riche en adenine pendant 4 semaines et avec de la saline pendant 12 semaines) et le groupe aliskiren-adenine (animaux ayant recu de l'adenine pendant 4 semaines et de l'aliskiren 10 mg/kg pendant 12 semaines). Les auteurs ont trouve que l'adenine provoquait une diminution significative du poids corporel, de l'Hb, du RC, du [Ca.sup.2+] serique, de l'expression d'eNOS et de nrf2, du GSH et de la catalase dans les tissus renaux, et un accroissement significatif de la pression arterielle (PA), de la creatinine serique, de l'AUS, de l'activite de la renine plasmatique (ARP), du [K.sup.+] et du P, de l'excretion d'albumine dans l'urine (EAU), de la caspase-3 et du MDA (un marqueur de la peroxydation lipidique) dans les tissus renaux, comparativement au groupe normal (p < 0,05). L'administration d'aliskiren provoquait un amelioration significative de tous les parametres etudies comparativement au groupe adenine (p < 0,05). Les auteurs concluent que l'aliskiren exerce un effet nephroprotecteur contre la nephropathie induite par l'adenine. Il pourrait etre du a l'inhibition de l'ARP, a l'attenuation du stress oxydant, a l'activation des genes Nrf2 et eNOS et a la suppression de la caspase-3. [Traduit par la Redaction] Mots-cles: adenine, nephropathie, nrf2, caspase-3, eNOS, stress oxidant., Introduction Nowadays, chronic kidney disease (CKD) is a worldwide health problem and one of the leading causes of death (Levey et al. 2007). Over the past decades, there is an [...]

Acute ischemia-reperfusion JR) of the limbs initiates both local and systemic injuries by triggering a systemic inflammatory response. Cyclooxygenase-2 (COX-2), an endogenous inducible enzyme, rises in response to inflammation. The aim of this work is to investigate the role of celecoxib, a selective COX-2 inhibitor, in abrogating remote organ dysfunction after hindlimb IR in rats by comparing it with a standard hemorrheologic drug (pentoxifylline). Rats were divided into 4 groups (n = 6 each), group I (sham control, received saline and was kept under anaesthetic for 7 h). Group II JR, subjected to 1 h of hindlimb tourniquet ischemia and 6 h reperfusion). Group III and IV (pretreated with 200 mg/kg pentoxifylline or 10 mg/kg celecoxib, respectively, intragastrically for 7 days before IR induction). Administration of pentoxifylline or celecoxib produced significant reduction in SGPT, serum creatinine, malondialdehyde, and tumor necrosis factor-a and significant increase in blood pH, blood adenosine triphosphate, and reduced glutathione compared with the IR group (p < 0.05). There was no significant difference among the pretreated groups. Histopathologic findings of the IR lung showed alveolar destruction, inflammatory cells infiltration, mast cell degranulation, and necrosis of the gastrocnemius muscle fibres. These changes were attenuated in the pretreated groups. In conclusion, celecoxib can ameliorate IR induced remote organ injury to a similar extent as pentoxifylline through its antiinflammatory and antioxidant action. Key words: ischemia-reperfusion injury, cyclooxygenase-2 inhibitor, lung, hindlimb. Resume : Une ischemie/reperfusion (IR) aigue des membres provoque des lesions tant locales que systemiques en declenchant une reponse inflammatoire systemique. La cyclooxygenase-2 (COX-2), une enzyme inductible endogene, augmente en reponse a l'inflammation. Le present travail a eu pour but d'examiner le role du celecoxib, un inhibiteur selectif de COX-2, dans la suppression de la dysfonction des organes a distance apres une IR des membres posterieurs de rats, en comparant ses effets a ceux d'un medicament hemorrheologique standard (pentoxifylline). On a divise les rats en quatre groupes (n = 6 par groupe) : groupe 1 (temoin opere de maniere fictive, a recu une solution saline et a ete maintenu sous anesthesie pendant 7 h); groupe II (IR, soumis a une 1 h d'ischemie des membres posterieurs au moyen d'un garrot, puis a 6 h de reperfusion); groupes III et IV (pretraites, ont recu 200 mgikg de pentoxifylline ou 10 mg/kg de celecoxib par voie intragastrique pendant 7 jours avant l'induction de l'IR). L'administration de pentoxifylline ou de celecoxib a provoque une diminution significative des taux de SGPT, creatinine serique, malondialdehyde et facteur de necrose des tumeurs a et une augmentation des taux de pH sanguin, adenosine triphosphate et sanguin et glutathion reduit sanguins comparativement aux valeurs observees chez le groupe soumis a l'IR (p < 0,05). Il n'y a pas eu de difference significative au sein des groupes pretraites. Les resultats histopathologiques du poumon IR ont montre une destruction alveolaire, une infiltration cellulaire inflammatoire, une degranulation mastocytaire, et une necrose des fibres musculaires du gastrocnemien. Ces modifications ont ete attenuees chez les groupes pretraites. Ainsi, le celecoxib, par son action antiinflammatoire et antioxydante, peut diminuer la lesion des organes a distance induite par l'IR, a un degre similaire a celui de la pentoxifylline. Mots-cles : lesion d'ischemie-reperfusion, inhibiteur de la cyclooxygenase-2, membres posterieurs. [Traduit par la Redaction], Introduction Surgical procedures of the extremities requiring application of a tourniquet, for example, those involved in vascular reconstructions, subject the limb to prolonged periods of ischemia followed by reperfusion (IR). [...]

Background Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling. Materials and Methods A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg/kg). Diabetic rats were randomized into 4 subgroups (n=6–7): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial Ito channel α subunits, gap junction protein; Kv 4.2/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry. Results Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2/4.3 and Cx43 expression/distribution and prevented diabetes-related QTc interval prolongation. Conclusions We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced Ito channel expression, may underlie the QTc interval prolongation in high-fat diet/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and Ito channels in the diabetic rat heart. [ABSTRACT FROM AUTHOR]

Vascular dysfunctions in chronic kidney disease (CKD) include endothelial dysfunctions and vascular calcification (VC). In the present study, we examined the possible protective effect of nicorandil (potassium channel opener) on renal and vascular dysfunctions in a rat model of adenine-induced nephropathy and its underlying mechanisms. Thirty-four male Sprague-Dawley rats were randomly allocated into 3 groups: Control group, Adenine group (animals received high-adenine diet for 4 weeks), and Nicorandil group (animals received adenine for 4 weeks and nicorandil 1 mg/kg per oral for 4 weeks). The results showed significant reduction in the body weight, heart rate (HR), hemoglobin contents, serum Ca2+ and reduction in the expression of mRNA of endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid related factor 2 (nrf2) genes in aortic tissues with significant increase in arterial blood pressure (ABP), serum creatinine, blood urea nitrogen (BUN), plasma renin activity (PRA), K+ and phosphate (PO4 3-), urinary albumin excretion (UAE) and aortic VC in Adenine group compared to normal group (p < 0.05). On the other hand, coadminsitration of nicorandil caused significant improvement in the studied parameters compared to Adenine group (p < 0.05). We concluded that nicorandil has a potential protective effect against the vascular and renal impairment induced by adenine, which might be due to attenuation of vascular calcifications, activation of Nrf2 and eNOS genes in aortic tissues. [ABSTRACT FROM AUTHOR]

Insulin resistance predicts development of type 2 diabetes mellitus (DM). Adipocytes release tumor Necrosis factor-alpha (TNF-α), and adiponectin. They modulate whole-body insulin sensitivity. The disturbance in the relationship between good and bad adipokines may cause insulin resistance. The renin-angiotensin aldosteron system (RAAS) plays a role in DM and the consequence of cardiovascular complications development. It is considered as a target for therapy. The present objective examined the relationship between renin angiotensin system and DM. There were, Group (1): Normal non obese rats, Group (2): Obese diabetic rats, Group (3) : Obese diabetic rats with telmisartan, Group (4): Obese diabetic rats with enalapril, Group (5): Obese diabetic rats with aliskiren. There was a significant increase in serum glucose, lipid profile [triglycerides (TGs), low-density lipoprotein cholesterol (LDL), total serum cholesterol (TC)], tumor Necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and a significant decrease in adiponectin associated with minor changes in superoxide dismutase (SOD) activity in the obese diabetic rats. Administration of telmisartan, enalapril and or aliskiren caused a significant improvement in serum lipid profile and adiponectin, a minor improvement in SOD activity, a decrease in TNF- α and or MDA. Conclusion: Renin angiotensin blockers significantly improve the metabolism and oxidative dysfunctions in Type 2 DM and aliskiren may show a promising powerful therapy. [ABSTRACT FROM AUTHOR]

Background: Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling., Materials and Methods: A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg/kg). Diabetic rats were randomized into 4 subgroups (n=6-7): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial I to channel α subunits, gap junction protein; Kv 4.2/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry., Results: Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2/4.3 and Cx43 expression/distribution and prevented diabetes-related QTc interval prolongation., Conclusions: We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced I to channel expression, may underlie the QTc interval prolongation in high-fat diet/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and I to channels in the diabetic rat heart., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Unlabelled: A β3 adrenoceptor agonist plays an important regulatory role in stimulation of thermogenesis and lipolysis and it appears to have anti-ulcer and spasmolytic effects. So the present aim was to examine the effect of BRL 37344 (a selective B3 adrenoceptor agonist) on reflux esophagitis., Methods: Forty-eight rats were divided into twelve sham-operated with BRL 37344 and/or omeprazole with or without indomethacin. RE was induced in rats, then gastric acid output, pH, plasma nitric oxide (NO), esophageal PGE2, malondialdehyde (MDA) and reduced glutathione (GSH) were measured and the esophageal injury was assessed by macroscopic damage score., Results: Pretreatment with BRL significantly increased plasma NO, GSH, decreased acid output, esophageal MDA and esophageal injury in comparison to pretreatment. In addition, there was a no significant increase in esophageal PGE2., Conclusion: It can be concluded that BRL 37344 has an anti-oxidant protective effect in rats with RE.