Alkaline Water Mitigates Bone Loss in Streptozotocin-Induced Type II Diabetic Rats.

Background A decline in bone mineral density is a defining feature of osteoporosis, which is a prevalent bone complication associated with diabetes. This study aims to shed light on the protective effect of Zamzam water (ZW), a famous alkaline water, on diabetes-induced osteoporosis. Methodology Of a total of 40 male rats, 10 male rats each were divided into the following four groups: group I (normal control rats), group II (ZW group), group III (diabetic rats), and group IV (DM + ZW). Anteroposterior and lateral X-rays were taken of the rats in each group before the end of the experiment. The study assessed serum levels of inflammatory markers including interleukin 6, interleukin-1 beta, and tumor necrosis factor-alpha; bone formation markers including osteocalcin (OC); alkaline phosphatase (ALP); and bone resorption markers including the N-terminal telopeptide of collagen type I (NTX-1), bone deoxypyridinoline (DPD), and tartrate-resistant acid phosphatase 5b (TRAP-5b). Results Rats with diabetes who consumed ZW exhibited a significant (p < 0.001) increase in OC and ALP bone formation markers and a decrease in NTX-1, DPD, and TRAP-5b bone resorption markers, with improvements in the X-ray image of the vertebral column at the L6 vertebra level. Conclusions ZW improved diabetes-induced osteoporosis in rats by enhancing osteoblastic activity and downregulating osteoclastic activity.

Anxiolytic and antidepressant like effects of Zamzam water in STZ-induced diabetic rats, targeting oxidative stress, neuroinflammation, BDNF/ERK/CREP pathway with modulation of hypothalamo-pituitary-adrenal axis.

Introduction: Recent studies have reported a strong relationship between diabetes and anxiety- and depression-like behaviors; however, there is a lack of information on the underlying pathophysiology. Alkaline Zamzam water (ZW), which is rich in several trace elements, has neuroprotective properties. This study aimed to investigate the anxiolytic and antidepressant effects of ZW against diabetes-induced behavioral changes and shed light on the possible underlying mechanisms. Methods: Forty-eight rats were divided into four experimental groups (n = 12): group I (control group), group II (Zamzam water group), group III (diabetic group), and group IV (diabetic + Zamzam water group). Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin (STZ). At the end of the experiment, the forced swimming test (FST) was used to assess depression-like effects. The elevated plus maze test (EPMT) and open field test (OFT) were performed to evaluate anxiety-like behavior. Blood levels of the hypothalamic-pituitary-adrenal (HPA) axis were measured, and prefrontal cortex and hippocampal tissue samples were removed for histological, immunohistochemical, ELISA, and Q-PCR analyses. Results: ZW significantly decreased the immobility time in the FST, indicating an antidepressant effect (p < 0.001). Additionally, ZW significantly improved the OFT and open field entry (OFE) percentages in the EPMT, increasing center crossing and decreasing grooming and fecal boli in the OFT. This indicated an anxiolytic-like effect in diabetic rats with histological improvement. Interestingly, ZW significantly increased prefrontal cortical and hippocampal levels of antioxidant enzymes and the Nrf2/HO-1 pathway. It also modulated the HPA axis by increasing cortisol and corticotropin-releasing hormone (CRH) levels, with a decrease in ACTH and an increase in monoamine neurotransmitters. Furthermore, diabetic rats that received ZW showed a decrease in the inflammatory markers TNF-α and GFAP by immunohistochemistry and in the mRNA levels of NFκB, IL-1ß, and IL6. In addition, ZW downregulated the expression of the BDNF/ERK2/CREP pathway. Conclusion: Our results suggested a neuroprotective effect of ZW against diabetes-induced anxiety- and depression-like behaviors and explored the underlying mechanisms. These findings suggest a promising therapeutic strategy for patients with diabetes who experience anxiety and depression.

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.

Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article).

Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of therapeutic benefits of prophetic medicine remedies as adjuvant treatments to many different types of hematological disorders. Herein, we reviewed many published research studies throughout the literature to delineate the potential therapeutic benefits of prophetic remedies on hematological disorders. Several types of hematological disorders may benefit from prophetic medicine remedies that are rich in natural antioxidants that combat oxidative stress-induced harm e.g. nigella sativa, oral honey, camel milk and urine, Ajwa date fruits, olive oil, Zamzam water and figs. Many prophetic medicine remedies were reported to decrease the hematological cytotoxicity effects induced by different chemicals and are beneficial in treating anemias e.g. iron deficiency anemia, sickle cell anemia, thalassemia, coagulopathies and hematological malignancies as leukemia and myeloma. These remedies treat or alleviate the different hematological disorders using different mechanisms e.g. modulating the immune function, treating deficiencies of different substances, protecting against toxins-induced cytotoxicity, decreasing platelets aggregation, suppressing clotting factors activation, exerting antineoplastic effects (enhancing cancer cells cytotoxicity) and inhibiting angiogenesis. Prophetic medicine remedies exert clinically significant therapeutic benefits for treating COVID-19 pandemic, anemia, thrombosis, thalassemia and blood cancers without inducing toxicity or side effects.

Remineralization Effect of Zamzam Water on Initial Artificial Carious Lesion of Permanent Teeth.

INTRODUCTION: Chemical testing showed that Zamzam water is completely safe to drink and has health benefits due to its high percentage of sodium, calcium, magnesium, and many other minerals. The purpose of this study was to evaluate the remineralization effect of Zamzam water on extracted premolars using the Vickers Microhardness test. METHODS: Teeth samples (N=40) with artificially induced carious lesions were divided randomly into four groups: Study group (I) treated with agitated Zamzam water (n=10), study group (II) treated with non-agitated Zamzam water (n=10), control positive group (III) treated with sodium fluoride (n=10), and control negative group (IV) treated with deionized water (n=10). Teeth were subjected to microhardness testing before and after artificial demineralization and after remineralization treatment within the four groups. RESULTS: Following treatment with different solutions in both study and control groups, there was an increase in microhardness after remineralization but with varying degrees. The highest increase in microhardness was shown after remineralization with sodium fluoride followed by agitated Zamzam water. CONCLUSION: Zamzam water with agitation causes an increase in the microhardness of the enamel surface after demineralization. Zamzam water is an effective remineralizing agent in initial carious lesions, and its efficacy is comparable to that of sodium fluoride.

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.

Effect of Zamzam Water on Microhardness of Primary Tooth Enamel After Erosion Induced by Claritin Syrup: An In-vitro Study.

BACKGROUND: Dental erosion is an irreversible damage to hard tissues in the mouth due to acid dissolution not induced by microorganisms. Oral medications contributed to the etiology of dental erosion. Among these medications, antihistamine-containing syrups were reported to have a considerable erosive effect on hard dental tissues. OBJECTIVE: The objective was to evaluate the effect of Zamzam water on the microhardness of primary tooth enamel after erosion induced by Claritin™ syrup. MATERIALS AND METHODS: The present in-vitro study was conducted on 25 primary central incisor teeth. The labial surfaces of the specimens were prepared for microhardness testing. Baseline microhardness was measured first, then the samples were submerged in the erosive agent Claritin™ syrup, for 30 min every 12 h for 12 days. Thereafter, all the teeth were placed in Zamzam water for 30 min every 12 h for 12 days. The microhardness was measured by the Vickers hardness tester and expressed as Vickers microhardness value (VH). The measurements were completed three times for the same sample: baseline, after erosion, and after Zamzam treatment. Data were analyzed statistically using one-way repeated analysis of variance (ANOVA) followed by Tukey's post hoc test. RESULTS: The primary teeth included in this study showed a significant increase in their surface microhardness after Zamzam water treatment; the mean value of VH was increased from 33.12 ± 1.62 to 89.32 ± 8.52 (P-value <0.0001). CONCLUSION: Zamzam water could be introduced as a part of the management of dental erosion in the primary dentition.

Statistical analysis of 222Rn concentration in Zamzam and other water sources in the Kingdom of Saudi Arabia.

In the present study, six water samples were collected from different locations in the Kingdom of Saudi Arabia and another sample from the Zamzam site in Makkah city. The concentration of the radioactive isotope 222Rn was measured using the electronic radon detector (RAD7). The comparative analysis study on these samples showed that the average concentration value in all samples was 0.504Bq/L. The data analysis showed that the concentration of 222Rn was ranged from 0.43 ± 0.06 Bq/L to 0.57 ± 0.060 Bq/L for all samples. These levels are below the contamination threshold (11.1 Bq/L) recommended by the US Environmental Protection Agency (EPA). Interestingly, Radon radioactivity levels were lower than those harmful to human health. The principal component analysis (PCA) using (SPSS version 15) was used to reduce the four variables influencing the 222Rn activity concentration to two variables: temperature (correlation coefficient, R2: 0.984) and the relative humidity (RH%) (R2:-0.987). The increase in temperature reduces the solubility of 222Rn gas activity water and facilitates its detection, whereas increased the RH% increases its solubility and decreases the detection level of 222Rn activity concentration. The interaction between temperature and RH% does not affect the concentration of 222Rn.

Investigation of the impacts of zamzam water on streptozotocin-induced diabetic nephropathy in rats. In-vivo and in-vitro study.

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

Biochemical and histological effects of five weeks ingestion of Zamzam water on the liver and kidneys of Wistar rats.

Zamzam water is a natural alkaline water which has become alkaline as a result of the natural environment. It comes from what is considered as one of the oldest springs in the world. The water contains high concentrations of alkaline minerals as well as trace and heavy metals. The aim of the current study is to evaluate the effects of five weeks ingestion of Zamzam water on the liver and kidney functions of rats. Adult female Wistar rats weighing 150-200 g were divided into two groups, with 15 rats in each. The control group was supplied daily by bottled water and the Zamzam water group was supplied daily by 500 ml of Zamzam water for five weeks. The rats were weighed weekly and, at the end of the experiment, blood samples were collected from all rats for the biochemical determination of serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine, albumin, and uric acid, using calorimetric methods. Liver and kidney tissues were fixed in 10% neutral buffered-formalin solution and further embedded in wax blocks for routine hematoxylin and eosin (H&E) staining and were examined for histopathological changes using a light microscope. The results of the current study showed that there was a significant increase (P < 0.05) in the weight of the Zamzam group when compared to the control group after five weeks of ingestion. Liver and kidney function tests did not show any significant difference when compared with the controls (P > 0.05). In addition, histological examination of the liver and kidney tissues did not show any toxicological changes. In conclusion, the results showed that the ingestion of Zamzam water did not alter serum levels of kidney function tests and liver enzymes; and did not result in a noticeable change in the liver and kidney histology. Thus, the high concentrations of elements in Zamzam water do not induce hepatotoxicity or nephrotoxicity and the water is considered safe for long-term consumption.

Chemical composition of Zamzam water: A comparative study with international standards of drinking water.

Studies conducted on the chemical composition of Zamzam water are conflicting especially for arsenic. Therefore, the aim of our study is to study the composition of tap and bottled Zamzam water and to compare its quality according to international guidelines of drinking water. Six Zamzam tap water samples as well as one bottled sample were analyzed according to standard methods (APHA) for their chemical constituents (pH, TDS, Na, K, Mg, Ca, Fe, Cu, Zn, Cd, Pb, Mn, Al, As, Cl-, SO4 -2, HCO3 - and PO4 -3). The results were compared to guidelines of WHO and EPA for quality of drinking water. All analyzed parameters were below the maximum allowable limits (MAL) of WHO and EPA (p˃0.05), with the exception of TDS. The average values of TDS (814 mg L-1 in tap zamzam water samples and 812 mg L-1 in bottled sample) were below the MAL of WHO (1000 mg L-1) but exceeded the limit that defined by EPA as a non-enforceable guidelines (500 mg L-1) (p˂0.05). Compared to the collected tap zamzam water samples, bottled sample had significantly lower levels of Na, PO4 -3 (p˂0.05) and Cu (p˂0.01). The study concluded that Zamzam water has acceptable chemical composition including arsenic, except for TDS that exceeds the high non-enforceable accepted limit according to EPA.

Acute effects of Zamzam water on blood pressure and heart rate variability.

OBJECTIVE: There is a lack of studies exploring the effects of Zamzam water on human physiology. The present study determined the effects of Zamzam water on blood pressure and heart rate variability (HRV). METHODS: This comparative interventional study was conducted at the Department of Physiology, of our university in March 2018. A total number of 97 female subjects drank 500 ml of either Zamzam water or mineral water in one minute. Finometer Pro and PowerLab (ADInstrumentsR) with ECG electrodes through bioamplifier and attached finger pulse transducer were used to collect data at the baseline (for five minutes), during (for one minute) and after the drink (for five minutes). Paired and uunpaired student's t-test, one-way ANCOVA and one-way repeated measure ANOVA were used for analysis. Blood pressure parameters were followed minute by minute and HRV parameters were compared as a 5-minute of baseline segment to 5-minute post drink segment. RESULTS: Within-the-group comparison exhibited significant increases in blood pressure parameters (systolic, diastolic, pulse and mean arterial pressure), over a 5-minute post-drinking period in both groups. Zamzam water caused a significant increase in SDRR (an indication of overall HRV) and RMSSD (an indication of vagal activity) as compared to baseline. CONCLUSION: Both drinks cause a significant increase in systolic, diastolic, pulse and mean arterial pressure within five minutes post-drinking period. Zamzam water produce a significant increase in cardiac vagal tone but has no effect on cardiac sympathetic activity. Mineral water has no significant effect on both, cardiac vagal and sympathetic activity.

Zamzam water is pathogen-free, uricosuric, hypolipidemic and exerts tissue-protective effects: relieving BBC concerns.

Zamzam water is the most frequently used drinking water by millions of people in Saudi Arabia. It is carried all the time by millions of pilgrims to their home countries as gifts to close and near relatives and friends. Safety of constituents of Zamzam water is a vital health topic. British Broadcasting Corporation (BBC) raised many health concerns regarding the high serum arsenic and nitrate contents in Zamzam water that may cause cancer. It is role of scientific research to present scientific facts to relieve such concerns. Arsenic is a carcinogen while nitrate causes methemogloinemia that affect oxygen carriage by haemoglobin. An ethical committee approval was obtained. Eighteen white albino mice (40-45 g) were used in this study. Three experimental groups were allocated (six mice per group): tap water group, distilled water group and Zamzam water group. Our data revealed that Zamzam water exerts tissue-protective effects that contradict malignancy. Our data proved that Zamzam water is pathogen-free causing no bacterial growth on CLED agar colonies. Zamzam water consumption for three consecutive months in mice was quite safe for the general health and significantly decreased serum uric acid (p < 0.05) (possibly due to Zamzam-induced urine alkalinisation facilitating uric acid excretion). Regular Zamzam water consumption significantly decreased serum cholesterol (p < 0.05) and serum triglycerides (p < 0.05). Hypolipidemic effects of Zamzam water may be due to its high mineral content facilitating increased lipids metabolism. Our data confirmed safety of prolonged use of Zamzam water comparable to other drinking water types regarding the metabolic and synthetic functions of the liver. Nitrates in Zamzam water are thought to be an original constituent that may be useful (exerting vasodilation, antithrombotic, and immunoregulatory effects) and not harmless. This may occur due to high Zamzam content of calcium, magnesium and selenium. Histologically, our data confirmed that Zamzam water was quite safe to renal parenchyma and comparable to other types of drinking water. In conclusion, health concerns raised by BBC regarding Zamzam water safety were a good chance for fruitful scientific research investigations that confirmed safety and beneficial effects of Zamzam water for human health.

Antiproliferative and apoptotic effects of the natural alkaline water (Zamzam) in breast cancer cell line MCF-7.

BACKGROUND: Zamzam water (ZW) is a natural alkaline water that contains several minerals that may represent a powerful tool for cancer therapy. OBJECTIVES: In this research, in vitro antiproliferative and apoptotic effects of ZW were investigated in the human breast cancer cell line MCF-7. MATERIALS AND METHODS: This study was conducted between January 2015 and February 2016. The effects of ZW on the morphology and the cell viability of human breast cancer cell line MCF-7 were determined. The cell death type and cell cycle changes were investigated using flow cytometry. Finally, reactive oxygen species (ROS) were also measured by fluorometric technique. RESULTS: MCF-7 cells treated with either ZW with adjusted pH at 7.2 or unadjusted pH at 8 showed reduced cell viability of cancerous cells. The cell death occurred through the apoptosis pathway under both treatment conditions. The treated MCF-7 cells were arrested in the G2/M phase and decreased in the G1 phase. Only the unadjusted pH ZW sample demonstrated an increase in the production of both cytoplasmic and mitochondrial ROS in MCF-7 cells. CONCLUSION: All the results in the present study indicated, for the first time, that ZW might have anticancer and apoptotic effects on breast cancer cell line.

Zamzam water protects cancer cells from chemotherapy-induced apoptosis via mitogen-activated protein kinase-dependent pathway.

BACKGROUND: Many Muslims believe that water from the Zamzam well is the cure for every disease. Zamzam water (ZW) is naturally alkaline water consumed by millions of people worldwide. The current study investigated the effect of ZW on cell viability and apoptosis in breast, colorectal and ovarian cancer cell lines and compared the effect with that of drinking water (DW). METHODS: Three different ZW samples collected from different sources at different periods were used. To balance the tonicity, ZW and DW were buffered using PBS and the pH was adjusted to 7.4. For the treatment, ZW and DW were diluted to 50% with RPMI medium (10% FBS). Cancer cell lines were treated with ZW or DW, with and without chemotherapeutic agents, for 24 h. Apoptosis was measured using flow cytometry whilst the level of protein expression was determined by Western blotting. RESULTS: The results showed that treatment with ZW significantly increased cell proliferation compared to DW control. Treatment with ZW significantly suppressed the effect of chemotherapeutic agents on decreasing cell viability and inducing apoptosis in all the cancer cell lines compared to chemotherapeutic agents alone treated in DW. Furthermore, ZW treatment increased the phosphorylation of CRAF, MEK1/2, ERK1/2 and P38 proteins in these cell lines. Notably, treatment with ZW suppressed the effect of chemotherapy-induced reduction of CRAF, MEK1/2, ERK1/2 and P38 phosphorylation in breast and ovarian cancer cell lines. We also showed that silencing of ERK1/2 significantly increased the chemotherapy-induced apoptosis in breast and colorectal cancer cell lines. These data suggest that MAPK proteins; especially activated ERK1/2 may play a role in ZW mediated suppression of chemotherapy-induced cell death. CONCLUSIONS: These findings clearly demonstrate that ZW protects cancer cells from chemotherapy-induced apoptosis through activation of the ERK1/2-MAPK signaling pathway.

In-vitro Study: Camp Overshoot Caused by Chronic Morphine Alleviated by the Synergistic Combination of Zamzam Water and Methadone in Human Primary Glioblastoma Cell Line (U-87 MG)

@#Introduction: Zamzam water is blessed water originated from Mecca and is believed by Muslims to have the ability to cure illness. This ability to cure illness is due to the fact that zamzam water has higher concentration of minerals especially sodium, calcium and magnesium which play a vital role. Sodium is reported to be involved in the regulation of the Mu-Opioid Receptor, which indirectly leads to the production of cAMP. Hence, this current study was carried out to investigate the synergistic effects of zamzam water and methadone combination on cAMP levels in human primary glioblastoma cell line (U-87 MG) after chronic morphine administration. Materials and Methods: The time course and concentration of morphine on U-87 MG cell line was determined. The U-87 MG cell line was incubated with morphine (25 µL/mL) for 24h, to make the cell dependent on morphine and later treated with different combinations of 3.2 mL of zamzam water and methadone (5, 10, 25 µL/mL). The levels of cAMP was determined using the enzyme-linked immunosorbent assay kit. Results: The result revealed that 3.2 mL of zamzam water incubated with 10 µl/ mL of methadone significantly prevented the overshoot production of cAMP level (p<0.05) in U-87 MG cell line after 48h incubation when compared to the untreated samples. Conclusion: These finding suggest that co-treatment with zamzam water and methadone could possibly avoid tolerance and dependence on chronic morphine treatment by preventing the up-regulation of cAMP level.

Effects of perinatal exposure to Zamzam water on the teratological studies of the mice offspring.

Zamzam water is well documented for plenty of medicinal value for curing illness. In the present study, the effects of perinatal consumption of Zamzam and normal drinking water by the pregnant mice on their offspring's physical parameters, early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE) activity in the homogenize brain tissue and blood parameters were compared. To achieve that; Zamzam water was given to female Swiss-Webster strain mice as the only source of drinking fluid and the control animals were administered plain tap water. Treatment started from the first day of pregnancy and continued until the postnatal day fifteen of delivery. All offspring were subjected to various tests. The rate of body weight gain remained relatively unaffected until the second week of weaning period, however; in the last week the offspring exposed to Zamzam water gained significant body weight as compared to their control offspring. Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed pups remained unaffected as compared to the controls. The sensory motor reflexes in Zamzam exposed pups after birth and during the first two weeks of weaning period were significantly increased. Locomotor Activity Test performed in the male and female offspring after weaning period showed a significant decrease in the male and increase in the female on most of the elements of this test due to Zamzam exposure. AChE activity in the homogenized brain tissue and blood parameters were unaffected as compared to the controls, the present Zamzam effects in the offspring are possibly via in utero action and/or via mother's milk.

Radioprotective effect of Zamzam (alkaline) water: A cytogenetic study.

BACKGROUND: Radioprotectors are useful compounds to reduce radiation toxicity of normal cells. Many natural radioprotectors have antioxidant power and display fewer toxicity and side effects than the chemical ones. Alkaline waters such as Zamzam have antioxidant power potentially. This study aimed to investigate the radioprotective effect of Zamzam water in mice bone marrow exposed to gamma radiation by micronuclei test. METHOD: Five study groups including control group which was fed by ordinary water, the second group was fed by Zamzam water, and radiation groups were received 2Gy gamma with ordinary and Zamzam water for 10 days and another for 20 days. The frequency of micronuclei and polychromatic erythrocytes to normochromatic erythrocytes ratio were calculated by micronuclei test. RESULT: In the absence of radiation, no significant difference was found between Zamzam group and control in the number of micronuclei in normochromatic erythrocytes, micronuclei in polychromatic erythrocytes, and the polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte ratio. But all of these indices were significantly different between irradiated and non-irradiated groups. The frequency of micronuclei in polychromatic erythrocytes was not significantly different between 10 and 20 days Zamzam irradiated groups, but the reduction in micronuclei in normochromatic erythrocytes and an increase in the polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte ratio compared to ordinary water were seen in 20 days Zamzam group. Dose reduction factor was 1.36 and 2 for Zamzam water groups of 10 days and 20 days, respectively. CONCLUSION: The results demonstrated that Zamzam alkaline water could reduce clastogenic and cytotoxic effects of gamma irradiation.