Novel Insights about Synergistic Effect of Zamzam Water with SGL2 Inhibitors on Wound Healing in STZ-Induced Diabetic Rats: The Role of anti-Inflammatory and Proangiogenic Effects.

Background: Hyperglycemia usually impairs wound healing by dysregulating the inflammatory response and angiogenesis. This study aimed to examine the synergistic effect of dapagliflozin and Zamzam water (ZW) on the healing of diabetic wounds and to explore their anti-inflammatory and proangiogenic effects.Materials and methods: A full-thickness excisional wound was made on the backs of all groups after two weeks of diabetes induction. Forty rats were divided into five groups, with eight rats per group; Group 1: Control non-diabetic rats; Group II: Untreated diabetic rats; Group III: Diabetic rats drinking ZW; Group IV: Diabetic rats receiving an oral dose of 1 mg/kg dapagliflozin; and Group V: Received both dapagliflozin and ZW. The healing of diabetic wounds was assessed by measuring wound closure, oxidative stress markers, immunohistochemical staining of NF-ßB, VEGF, CD34, CD45, Ki-67, and eNOS, gene expression of MMP-9, TGF-ß1, EGF-b1, FGF, and Col1A1, protein levels of TNFα, IL-1ß, IL6, Ang II, and HIF-1α by ELISA assay, and histological examination with H & E and Masson's trichrome. Combined treatment with dapagliflozin and ZW significantly (p < 0.05) enhanced the wound closure and antioxidant enzyme level, with apparent histological improvement, and shortened the inflammatory stage of the diabetic wound by decreasing the level of inflammatory markers NF-κB, TNF-α, IL-1ß, IL6, and CD45. Therefore, it improved angiogenesis markers VEGF, CD34, eNOS, EGF-ß1, FGF, Ang II, and HIF-1α, increasing Ki-67 cellular proliferation. Moreover, it enhanced the remodeling stage by increasing MMP-2, TGF-ß1, and Col1A1 levels compared to diabetic rats.

Zamzam Water Ameliorates Gentamicin-Induced Testicular Toxicity in a Rat Model via Targeting Sperm Parameters, Testicular Tissue Oxidative Insult, Inflammation, Apoptosis, and Pituitary-Gonadal Axis.

Gentamicin is considered one of the most typical causes of testicular damage. Oxidative stress is a significant contributor to testicular tissue damage. Zamzam water (alkaline in nature) has an antioxidant effect. The purpose of this study was to assess the potential palliative effect of Zamzam water against gentamicin-induced testicular damage. Thirty Rats were separated into three groups, each with ten rats, as follows: The Control received only normal saline. The gentamicin group received 100 mg/kg/day of gentamicin intraperitoneally for six days from day 15 to the end of the experiment. The gentamicin +Zamzam Water group received a dose of gentamicin 100 mg/kg/day intraperitoneally with Zamzam water as their sole source of drinking from day one to day 21. Hormonal assay in serum, histological, immunohistochemical, and ultrastructural examination of testicular tissue with a molecular study were obtained. Pretreatment with Zamzam water significantly p < 0.001 increased serum levels of testosterone, FSH, and LH, as well as the percentage of sperm motility and progressive motility. It also upregulated SOD, CAT, GPx enzymatic activity, gene expression of Nrf2/HO-1, and immunoexpression of PCNA. While the percentage of dead sperm and abnormal sperm, immunoexpression of NFκB, Caspase 3, inflammatory cytokines TNFα, IL-1ß, IL-6, and MDA levels significantly (p < 0.001) declined with histological improvement. It was concluded that Zamzam water as alkaline water possesses antioxidant, anti-inflammatory, and antiapoptotic effects against gentamicin-induced testicular toxicity in vivo.