Protective effect of resveratrol on methylglyoxal-induced endothelial dysfunction in aged rats.

BACKGROUND: The cardiovascular benefits of resveratrol (RSV) have been well established by previous experimental and clinical studies. The aim of this study was to investigate the effectiveness of RSV administration on the impaired endothelial function induced by methylglyoxal (MGO), and to elucidate the role of endothelial nitric oxide synthase (eNOS) on its protective effect. METHODS: Aged Wistar rats (80 weeks old, n = 15) were used in this study. The thoracic aorta was isolated and cut into rings for organ culture. Aortic segments of rats were incubated with MGO (420 µM) in the presence or absence of RSV (30 µM) for 4 h (short-term) or 24 h (long-term). Isometric tension studies were performed by an isolated organ bath in response to acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium nitroprusside (SNP, an endothelium-independent vasodilator). Beside, expressions of eNOS and phospho-eNOS (p-eNOS) (Ser 1177) in thoracic aorta rings were evaluated by immunohistochemistry. RESULTS: Both short-term and long-term MGO incubation significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. In addition, eNOS and p-eNOS expressions decreased significantly in arteries incubated with MGO. The impaired endothelial reactivity as well as decreased expressions of eNOS and p-eNOS in MGO-incubated vessels were significantly improved by RSV treatment. CONCLUSIONS: Endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by MGO administration, and RSV may improve vascular endothelial function. The protective effect of RSV against MGO-induced endothelial dysfunction seems to be via increased eNOS expression and activity.

Inhibition of poly(ADP-ribose) polymerase may have preventive potential for varicocoele-associated testicular damage in rats.

Varicocele is ordinarily accompanied by testicular damage and male infertility. Several theories have been proposed to explain the detrimental effect of varicocele on testis tissue, including the possible effects of oxidative stress. The poly(ADP-ribose) polymerase (PARP) pathway has been established as a major downstream intracellular pathway of oxidative stress. Recently we have reported that PARP pathway has been activated in varicocele-induced rat testicular damage model. The aim of the present study was to investigate the possible protective effect of PARP inhibition in varicocele-associated testicular damage. Fifty male Wistar rats were divided into five groups: control, sham, varicocele-induced, varicocele-induced 1,5-isoquinolinediol (ISO, a PARP inhibitor)-treated, and ISO treated groups. The ISO-treated rats received intraperitoneal injections of 3 mg/kg ISO daily for 13 weeks. After 13 weeks of varicocele induction, body and testes weights were investigated in all groups. Histopathology of testes were evaluated by light microscopy. Expressions of PAR, p53 and cytochrome c were detected by immunohistochemistry and cleaved PARP-1, PAR, p53 and cytochrome c by western blot. The degree of apoptosis was determined by TUNEL. Light microscopy revealed testicular damage comprising various degrees of seminiferous tubule degeneration in varicocele-induced rats and their testes weights decreased significantly, whereas ISO administration prevented it. Expressions of cleaved PARP-1, PAR, cytochrome c, and p53 increased significantly in varicocele-induced rats, whereas the level of these molecules were similar to controls in varicocele-induced rats treated with ISO. In conclusion, increased PARP activation in testes seems to be related with testicular damage and apoptosis associated with varicocele and pharmacological inhibition of this pathway might be an effective intervention to prevent varicocele-induced testicular injury.

Resveratrol reverses diabetes-related decrement in sildenafil-induced relaxation of corpus cavernosum in aged rats.

BACKGROUND: The aim of this study was to investigate the effect of resveratrol (RVT) on sildenafil-induced relaxations of isolated corpus cavernosum in non-diabetic and diabetic aged rats. METHODS: A total of 13 male aged rats (72-80 weeks old) were randomized into two groups including non-diabetic aged rats and diabetic aged rats. Diabetes was induced in aged rats by streptozotocin (single i.p. dose of 45 mg/kg body weight) administration. At the end of the 12th week, corpus cavernosum strips of rats were suspended in an organ bath system. The corpus cavernosum relaxation was evaluated by sildenafil in the presence or absence of RVT (10-4 M) for 45 min. RESULTS: Induction of diabetes resulted in significant inhibition of sildenafil-induced corpus cavernosum relaxation in aged rats. The diminished relaxation in response to sildenafil was significantly improved by acute RVT incubation in both non-diabetic and diabetic aged rats; however, the magnitude of potentiation induced by RVT was more pronounced in diabetic aged rats. The potentiating effect of RVT was significantly inhibited by L-NG-nitroarginine methyl ester (L-NAME, 10-4 M, for 30 min) incubation in both groups. After the L-NAME incubation, the relaxation response of corporal tissues evoked by sildenafil was found to be similar in diabetic and non-diabetic aged rats. CONCLUSIONS: RVT improves sildenafil-induced relaxations of corpus cavernosum in both diabetic and non-diabetic aged rats probably by potentiating the activity of NOS, and this effect seems to be more manifest in diabetic aged group.

Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: a study on farmworkers in Antalya (Turkey).

Environmental exposure to pesticides may cause serious health risks including fertility and reproductive function. The aim of this study was to highlight whether there is a relationship between exposure to abamectin and male fertility parameters of farmworkers. Twenty male farmworkers who were using abamectin and 20 men not exposed to pesticides were recruited as experimental and control groups, respectively. Semen analysis, molecular markers of sperm maturity and serum reproductive hormone levels were evaluated. In experimental group, high plasma abamectin levels were detected. These men have decreased sperm motility. Moreover, diminished molecular markers of sperm maturity, such as decreased hyaluronic acid (HA) binding of sperm, increased numbers of aniline blue positive sperm and increased percentage of creatine kinase (CK) positive sperm, were observed in abamectin-exposed men. Their serum testosterone, LH and FSH levels did not change significantly. We conclude that exposure to abamectin may impair male fertility by effecting semen quality.

Experimental hyperhomocysteinemia disturbs bone metabolism in rats.

OBJECTIVE: To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. METHODS: Blood and urine samples were collected from rats fed with a methionine-enriched diet (HHCY, n = 18) or an isocaloric control diet (control, n = 10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N-terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RESULTS: HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2 micromol/L; p = 0.0006). Bone resorption parameters hydroxyproline (1.60 +/- 0.6 versus 0.85 +/- 0.4; p<0.05) and N-terminal collagen I telopeptides (150.8 +/- 78 versus 48.1 +/- 26 nmol/L BCE; p<0.05) increased, whereas bone formation marker osteocalcin (9.01 +/- 3.8 versus 15.07 +/- 4.2 ng/mL; p<0.05) decreased in HHCY compared to control rats. The relation N-terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14 +/- 3.1 versus 4.14 +/- 1.9). BMD measurement did not reveal any differences between groups. CONCLUSION: These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk.

Minimally invasive saphenous vein harvesting using a laryngoscope: procedural, functional, and morphologic evaluation.

BACKGROUND: Because commercial minimally invasive harvesting equipments significantly increase operation costs, they are not always available in all clinics worldwide. The aim of this study was to investigate whether minimally invasive saphenous vein harvesting using a laryngoscope can be applied efficiently and successfully. METHODS: Thirty patients were prospectively randomized into two groups. One group underwent a minimally invasive technique using a laryngoscope; the other, open saphenous vein harvest. A modified bridging technique, in which tissue retraction and illumination is achieved with a sterilized laryngoscope, was used for minimally invasive harvesting. Smooth muscle contractile and endothelial functions were tested in vitro using an organ chamber. Morphology was examined with light microscopy. RESULTS: There was no statistically significant difference in harvest times or length of the vein harvested by either of the above mentioned techniques. Total length of the incision in the minimally invasive group was significantly shorter than that in the open group. In follow-ups, no significant complications occurred in either group. Pain and leg edema were significantly less in the minimally invasive group compared to those of the open group. There was no significant difference in response to acetylcholine and 80 mM KCl between veins taken with the laryngoscope compared to veins taken with the traditional open technique. Similarly, histological data was unable to show any significant damage to the vessel wall. CONCLUSIONS: Because the laryngoscopic saphenectomy does not harm the harvested graft, it can be applied, instead of other minimally invasive saphenous vein harvesting systems, with a zero cost, efficiently, successfully, and with satisfactory speed and significant reduction of postoperative leg pain and wound complications.

The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteries.

1. The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2. Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10(-4) m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10(-5) m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l-NAME was reversed completely by l-arginine (10(-3) m), but not d-arginine (10(-3) m). 3. This NANC relaxation was attenuated by 8-phenyltheophylline (10(-5) m), a P1-purinoceptor antagonist. 4. The NANC response was potentiated by 10-6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 x 10-6 m milrinone, a type III PDE inhibitor. 5. Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6. Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7. These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension.

Effect of experimental diabetes on GABA-mediated inhibition of neurally induced contractions in rat isolated trachea.

1. In the present study, we investigated the effect of GABA and selective GABA agonists and antagonists on neurally induced tracheal contractions in streptozotocin (STZ) diabetic rats. 2. Contractile responses to electrical field stimulation (EFS) in rat tracheal rings were completely abolished by atropine and tetrodotoxin, but were unaffected by the ganglion blocker hexamethonium, indicating that they were mediated via neuronal release of acetylcholine (ACh). 3. Contractions induced by EFS, but not by exogenous ACh, were inhibited by GABA and the selective GABA(B) receptor agonist baclofen, but not by the selective GABA(A) receptor agonist 3-aminopropane sulphonic acid. The inhibitory effects of GABA or baclofen were not affected by the GABA(A) antagonist bicuculline, but were significantly reversed by the GABA(B) antagonist phaclofen. 4. The inhibitory effects of both GABA and baclofen were found to be significantly greater in trachea from control rats compared with tissues from diabetic rats. 5. Non-adrenergic, non-cholinergic relaxation responses elicited by EFS in precontracted tracheal rings from diabetic and control rats were similar in magnitude and were unaffected by GABA or GABA analogues. 6. These results suggest that GABA decreases the response to EFS by directly inhibiting the evoked release of ACh through GABA(B) receptors in rat trachea and that STZ-induced diabetes causes an impairment in the inhibitory effect of GABA on neurally induced contractions in this tissue.

The effect of experimental diabetes on cholinergic neurotransmission in rat trachea: role of nitric oxide.

We investigated the effect of nitric oxide (NO) on the responses of isolated tracheas to acetylcholine and to electrical field stimulation in streptozotocin-diabetic and controls rats. The contractile responses to acetylcholine were neither different nor affected by the NO synthase blocker, N(omega)-nitro-L-arginine methyl ester (L-NAME), in the two groups. Diabetic rat tracheas were supersensitive to field stimulation. L-NAME enhanced field stimulation-induced contractions at low frequencies in control rat tracheas, but had no effect in diabetic rat tracheas. After L-NAME treatment, there was no difference in sensitivity to field stimulation between the groups. The relaxation responses to sodium nitroprusside in acetylcholine-precontracted tracheas were not different between the groups. However, diabetic rat trachea was supersensitive to the relaxant effect of sodium nitroprusside on contractile responses to field stimulation. These results suggested that the increase in sensitivity to field stimulation in tracheas from diabetic rats might be due to impairment in the production and/or release of an endogenous NO-like factor.