Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum

Paskaloǧlu, Kübra; Şener, Göksel; Ayanğolu-Dülger, Gül

doi:10.1016/j.ejphar.2004.08.002

Cited by 67 publications

(55 citation statements)

References 40 publications

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“…51 Substantial experimental and clinical evidence exists for the involvement of ROS in the development of endothelial dysfunction in the diabetic penis. Penile tissue from diabetic men with ED and streptozotocin-induced diabetic rats contains lower levels of nitrate and nitrite, 56 higher levels of superoxide, 57 and higher levels of malondialdehyde, 56,58,59 a product of lipid peroxidation, compared to penile tissue from nondiabetic ED patients and nondiabetic animals. Inhibition of p38 mitogen-activated protein kinase (MAPK) partially corrects neurostimulated and endotheliumdependent relaxation of diabetic mouse corpus cavernosal strips.…”

Section: Oxidative Stressmentioning

confidence: 99%

“…62 In several diabetic animal models, decreased antioxidant levels, suggestive of oxidative stress, are measured in the penis, whereas antioxidant therapy leads to improved endothelial function and erectile ability. Vitamin E, sodium selenate, 63,64 ascorbic acid, 65 alpha-lipoic acid and gamma-linolenic acid, 66 and melatonin 56,58 restore neuronal and endothelial function in the corpus cavernosum. SOD and the metal chelator trientine also improve relaxation of diabetic corpus cavernosum.…”

Section: Oxidative Stressmentioning

confidence: 99%

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Endothelial dysfunction in diabetic erectile dysfunction

2006

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Erectile dysfunction (ED) is highly prevalent in diabetes mellitus. Pathophysiological mechanisms underlying diabetes-associated ED are in large part due to endothelial dysfunction, which functionally refers to the inability of the endothelium to produce vasorelaxing messengers and to maintain vasodilation and vascular homeostasis. The precise mechanisms leading to endothelial dysfunction in the diabetic vasculature, including the penis, are not yet fully understood. Hyperglycemia affects endothelial nitric oxide synthase activity and nitric oxide production/ bioavailability, nitric oxide-independent relaxing factors, oxidative stress, production and/or action of hormones, growth factors and/or cytokines, and generation and activity of opposing vasoconstrictors. Considering recent advances in the field of vascular biology and diabetes, the emphasis in this review is placed on the mechanisms of hyperglycemia-induced endothelial dysfunction in the pathophysiology of diabetes-associated ED.

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Section: Oxidative Stressmentioning

confidence: 99%

Section: Oxidative Stressmentioning

confidence: 99%

Endothelial dysfunction in diabetic erectile dysfunction

2006

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“…Enhanced oxidative stress over the antioxidant capacity of the body in some conditions is accepted to lead to endothelial dysfunction which may play a role in the pathophysiology of hypertension, and impaired endothelial function was shown to be restored by melatonin in these situations probably due to its antioxidative properties (23,24). Thus, it could be suggested that decreased melatonin concentrations may result in endothelial dysfunction in Px rats.…”

Section: Discussionmentioning

confidence: 99%

Vascular Reactivity to Various Vasoconstrictor Agents and Endothelium-Dependent Relaxations of Rat Thoracic Aorta in the Long-Term Period of Pinealectomy

2006

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Abstract. In this study, the effects of reduced melatonin concentrations in the long-term period of pinealectomy on mean arterial blood pressure (BP) and vascular responses in isolated rat thoracic aorta were investigated. Rats were pinealectomized (Px) two months before the beginning of the studies. Rings of endothelium-intact and -denuded rat arteries were mounted in isolated tissue baths for the measurements of isometric contractile force. No significant difference was determined between the arterial BP of Px (88.1 ± 1.9 mmHg) and control (83.8 ± 1.2 mmHg) rats. All arteries isolated from control and Px rats showed essentially identical contractions in response to phenylephrine, serotonin, calcium, clonidine, vasopressin, and angiotensin-II. Only endothelin-1 (ET-1)-induced contractions in the endothelium-denuded vessels isolated from Px rats were found to be increased to some extent. Pinealectomy did not affect acetylcholine or sodium nitroprusside-induced relaxation in the rat aorta either. These data suggest that reduced melatonin levels two months after pinealectomy did not modify either the vascular reactivity to various vasoconstrictor agents except the partially increased contractile responses to ET-1 in the endothelium-denuded thoracic aortas of Px rats or the endotheliumdependent and -independent relaxations in rat thoracic aorta. Restoration of the increased vascular responses to some vasoconstrictor agents, which were reported previously, may be the reason of why the hypertension is temporary following pinealectomy.

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“…Hence the administration of natural antioxidant, alpha-tocopherol was introduced with L-Norvaline to counteract this effect. Moreover it was reported that the level of SOD and glutathione peroxidase was highly diminished in diabetic condition [23]. Treatment with ɑ tocopherol alone showed the most promising effect on the SOD and reduced glutathione than the combination with L-Norvaline.…”

Section: Discussionmentioning

confidence: 99%

L-Norvaline and Alpha-tocopherol Treatment Protect Against Diabetes-Induced Oxidative Stress in Testes of Male Rats

De¹,

Singh²

2016

Reprod Syst Sex Disord

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The present study aimed to evaluate the effect of L-Norvaline and alpha-tocopherol in protection and combating the oxidative stress of testes in hyperglycemic male rats. In our study single dose of streptozotocin was used for induction of diabetes and fasting serum glucose level was checked and those animals showing FSG above 250 mg/dL were selected. The diabetic animals were randomly divided into seven groups comprising six animals in each group and one group of normal non diabetic animals received the vehicle 0.1 M citrate buffer pH 4.5. L-Norvaline was administered at higher (10 mg/kg) and lower (8 mg/kg) dose intraperitoneally to the different groups of diabetic animals along with alpha-tocopherol (900 mg/kg) orally for a period of 30 days. Sildenafil at an oral dose of 5 mg/kg was used as reference drug. After that period, testis was isolated and homogenized. The homogenized tissue was centrifuged, separating the supernatant and preserved it for assessing the oxidative stress parameters. The level of various antioxidant enzymes were assessed such as superoxide dismutase, reduced glutathione, glutathione peroxidase and glutathione reductase. Assessment of lipid peroxidation was also done in treated groups. The statistical analyses were carried out using Graph Pad Prism 5.0 software. All values were presented as Mean ± S.E.M. The level of superoxide dismutase, reduced glutathione, glutathione peroxidase and glutathione reductase were highly diminished in the diabetic rats compared with normal group. L-Norvaline alone showed no significant improvement in those enzymes parameters except in reduced glutathione (P<0.05). L-Norvaline both at higher dose and lower dose along with alpha-tocopherol showed significant improvement in the level of antioxidant enzymes as compared with diabetic group (P<0.05, P<0.01, P<0.001). Treated groups also showed a significant decrease in the level of malondialdehyde as compared to diabetic group (P<0.01, P<0.001). Standard drug, Sildenafil showed no improvement in any parameters after 30 days. The present can be concluded by establishing the fact that LNorvaline and Alpha-tocopherol could be a good combination in scavenging free radicals in testes due to streptozotocin induced hyperglycemia in male Wistar rats.

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Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum

Cited by 67 publications

References 40 publications

Endothelial dysfunction in diabetic erectile dysfunction

Endothelial dysfunction in diabetic erectile dysfunction

Vascular Reactivity to Various Vasoconstrictor Agents and Endothelium-Dependent Relaxations of Rat Thoracic Aorta in the Long-Term Period of Pinealectomy

L-Norvaline and Alpha-tocopherol Treatment Protect Against Diabetes-Induced Oxidative Stress in Testes of Male Rats

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