Orphanin FQ and glutamate connection in the regulation of gonadotropin-releasing hormone secretion in the preoptic area of conscious male rats.

Utilizing the method of push-pull perfusion and radioimmunoassay (RIA), the secretory profile of gonadotropin-releasing hormone (GnRH) in the preoptic area (POA) and serum-luteinizing hormone (LH) levels were examined in conscious male rats after administration of [Nphe(1)]NC(1-13)NH(2), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor) which is endogenous receptor for Orphanin FQ (OFQ). Glutamate release in the POA was also measured by high-performance liquid chromatography (HPLC) after perfusion of [Nphe(1)]NC(1-13)NH(2), i.e. NC13. The results showed that GnRH secretion from the POA and serum LH levels was increased significantly 40 min and 60 min, respectively after perfusion of 2 and 20 mmol/L NC13 in freely moving male rats (p<0.05). Pretreatment with a glutamate, N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801, s.c., 0.2 mg/kg) abolished the increase of GnRH release in the POA induced by 2 mmol/L NC13. Additionally, 20 mmol/L NC13 significantly enhanced glutamate release in the POA at 40 min post-perfusion in a dose-dependent manner. These findings suggest that hypothalamic OFQ/ORL1 receptor system plays a role in the physiological inhibitory control of GnRH secretion in the POA of male rats, and provide evidence for involvement of an OFQ and glutamate pathway in the control of GnRH secretion.

Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.

Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 µg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.

Plasma sRAGE is independently associated with high sensitivity C-reactive protein in type 2 diabetes without coronary artery disease.

Our studies suggest that plasma soluble advanced glycation end products (sRAGEs) has significantly negative association with high sensitivity C-reactive protein (hs-CRP) in 245 type 2 diabetes patients without diagnosed coronary artery disease (CAD). sRAGE maybe act as a novel biomarker for predicting the atherosclerosis in diabetes at the early stage.

Plasma sRAGE is not associated with urinary microalbumin excretion in type 2 diabetic nephropathy at the early stage.

AIMS: The interaction of advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE) has played an important role in the pathogenesis of diabetic nephropathy. In the present study, we measured the relationship of plasma soluble isoform of RAGE (sRAGE) and urinary microalbumin excretion in the early stage of type 2 diabetic nephropathy. METHODS: 180 patients with early stage of type 2 diabetic nephropathy were recruited into the study. Plasma sRAGE and the characterized AGE carboxymethyllysine (CML) were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma sRAGE positively correlated with the level of CML (R=0.22, P=0.03) while sRAGE was not significantly correlated with the urinary mAlb/Cr (R=0.15, P=NS). On stepwise linear regression analysis, AGE and GFR were the main independent determinants of plasma sRAGE concentration. CONCLUSION: Plasma sRAGE is not significantly associated with urinary microalbumin excretion in the early stage of diabetic nephropathy while it is correlated positively with circulating AGE and negatively with glomerular filtration rate (GFR).