Oxidative stress is considered the main event in the pathogenesis. of diabetic nephropathy (DN). Zamzam water, being natural alkaline with exceptional characteristics, is capable of enhancing antioxidant mechanisms. In this context; the present study has aimed to investigate the protective effects of zamzam water alone or in combination with gliclazide against the streptozotocin (STZ) induced DN model in rats.

DN was initiated by a single intraperitoneal dose of STZ. Three days later, diabetic rats were classified into 5 groups; a normal control group, a diabetic control group, a group receiving gliclazide, a group receiving zamzam water, and a group receiving both gliclazide and zamzam water. Blood pressure (BP) and heart rate (HR) were determined. Then rats were euthanized and serum was isolated for assessment of glucose, insulin, kidney function tests and nitric oxide (NO). Furthermore kidney contents of malondialdehyde (MDA) and reduced glutathione (GSH) were estimated. Histopathology or renal tissues and immunohistochemistry of caspase 3 were determined. In addition, islets of Langerhans were separated from normal rats by collagenase digestion method to study the effects of zamzam water on insulin release in-vitro. Furthermore, chemical analysis of zamzam water has been done.

Zamzam water significantly decreased STZ-induced hyperglycemia, BP, HR, oxidative stress biomarkers, impairment in renal functions (urea, creatinine, albumin), morphological changes in kidney and apoptosis. Likewise, zamzam water markedly elevated insulin levels both in in-vivo and in in-vitro experiments. The effects were more pronounced in combination with gliclazide.

Zamzam water has a promising renoprotective effect against STZ induced DN through its anti-diabetic, antioxidant, anti-inflammatory and anti-apoptotic potentials.