Role of Ang1-7 in renal haemodynamics and excretion in streptozotocin diabetic rats.

The contribution of angiotensin (1-7) (Ang1-7) to control of extrarenal and renal function may be modified in diabetes. We investigated the effects of Ang1-7 supplementation on blood pressure, renal circulation and intrarenal reactivity (IVR) to vasoactive agents in normoglycaemic (NG) and streptozotocin diabetic rats (DM). In Sprague Dawley DM and NG rats, 3 weeks after streptozotocin (60 mg/kg i.p.) or solvent injection, Ang1-7 was administered (400 ng/min) over the next 2 weeks using subcutaneously implanted osmotic minipumps. For a period of 5 weeks, blood pressure (BP), 24 h water intake and diuresis were determined weekly. In anaesthetised rats, BP, renal total and cortical (CBF), outer (OMBF) and inner medullary (IMBF) perfusion and urine excretion were determined. To check IVR, a short-time infusion of acetylcholine or norepinephrine was randomly given to the renal artery. Unexpectedly, BP did not differ between NG and DM, and this was not modified by Ang-1-7 supplementation. Baseline IMBF was higher in NG vs. DM, and Ang1-7 treatment did not change it in NG but decreased it in DM. In the latter, Ang1-7 increased cortical IVR to vasoconstrictor and vasodilator stimuli. IMBF decrease after high acetylcholine dose seen in untreated NG was reverted to an increase in Ang1-7 treated rats. Irrespective of the glycaemia level, Ang1-7 did not modify BP. However, it impaired medullary circulation in DM, whereas in NG it rendered the medullary vasculature more sensitive to vasodilators. Possibly, the medullary hypoperfusion in DM was mediated by Ang1-7 activation of angiotensin AT-1 receptors which are upregulated by hyperglycaemia.

Antioxidant Properties of Embelin in Cell Culture. Electrochemistry and Theoretical Mechanism of Scavenging. Potential Scavenging of Superoxide Radical through the Cell Membrane.

Embelin, a plant natural product found in Lysimachia punctata (Primulaceae), and Embelia ribes Burm (Myrsinaceae) fruit, possesses interesting biological and pharmacological properties. It is a unique chemical species as it includes both quinone and hydroquinone functional groups plus a long hydrophobic tail. By using hydrodynamic voltammetry, which generates the superoxide radical in situ, we show an unusual scavenging capability by embelin. Embelin as a scavenger of superoxide is stronger than the common food additive antioxidant 2,6-bis(1,1-dimethylethyl)-4-20 methylphenol, (butylated hydroxytoluene, BHT). In fact, embelin is even able to completely abolish the superoxide radical in the voltaic cell. Computational results indicate that two different types of embelin scavenging actions may be involved, initially through π-π interaction and followed by proton capture in the cell. A related mechanism describes embelin's ability to circumvent superoxide leaking by transforming the anion radical into molecular oxygen. In order to confirm its antioxidant properties, its biological activity was tested in a study carried out in THP-1 human leukemic monocytes and BV-2 mice microglia. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, proliferation curves and antioxidant activity by the use of a fluorescent probe showed good antioxidant properties at 24 h. This suggests that embelin's long alkyl C10 tail may be useful for cell membrane insertion which stimulates the antioxidant defense system, and cytoprotection in microglia. In conclusion, embelin could be an interesting pharmacological tool able to decrease the damage associated with metabolic and neurodegenerative diseases.