Safar Marwa M, Abdelsalam Rania M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Pharmacol Rep. 2015 Feb;67(1):17-23. doi: 10.1016/j.pharep.2014.08.001. Epub 2014 Aug 20.
Sulfurous mineral water and its main active ingredient sodium hydrosulfide (NaHS) are major sources of H2S. The present study aimed to explore their protective effect on one of the serious long-term complications of diabetes; diabetic nephropathy.
Sulfurous mineral water (as drinking water), NaHS (14 μmol/kg/day; ip), and gliclazide (10mg/kg; po) were administered daily for 6 weeks to streptozotocin (STZ)-diabetic rats.
STZ-induced diabetes was associated with body weight reduction, hyperglycemia, overproduction of glycated hemoglobin, as well as decline in serum insulin, C-peptide, and insulin like growth factor-I. Besides, diabetes impaired kidney functions and imposed oxidative and nitrosative stress as manifested by elevated contents of renal thiobarbituric acid reactive substances and nitric oxide, parallel to reduced glutathione content. These deleterious effects were antagonized by sulfurous water and to a better extent by NaHS. Activities of myeloperoxidase and sorbitol dehydrogenase were not altered by STZ or any of the treatments. However, STZ-induced diabetes was accompanied by an increment of aldose reductase which was only mitigated by gliclazide and NaHS. Histopathological examination of kidney sections corroborated the biochemical findings.
This study suggests a novel therapeutic approach for diabetic nephropathy using H2S donors.
含硫矿泉水及其主要活性成分氢硫化钠(NaHS)是硫化氢的主要来源。本研究旨在探讨它们对糖尿病严重长期并发症之一——糖尿病肾病的保护作用。
将含硫矿泉水(作为饮用水)、NaHS(14 μmol/kg/天;腹腔注射)和格列齐特(10mg/kg;口服)每日给予链脲佐菌素(STZ)诱导的糖尿病大鼠,持续6周。
STZ诱导的糖尿病与体重减轻、高血糖、糖化血红蛋白过量产生以及血清胰岛素、C肽和胰岛素样生长因子-I下降有关。此外,糖尿病损害肾功能并导致氧化应激和亚硝化应激,表现为肾硫代巴比妥酸反应性物质和一氧化氮含量升高,同时谷胱甘肽含量降低。这些有害影响被含硫水拮抗,NaHS的拮抗作用更好。髓过氧化物酶和山梨醇脱氢酶的活性未被STZ或任何一种治疗改变。然而,STZ诱导的糖尿病伴随着醛糖还原酶增加,只有格列齐特和NaHS能减轻这种增加。肾脏切片的组织病理学检查证实了生化结果。
本研究提示使用硫化氢供体治疗糖尿病肾病的一种新方法。