Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five milligrams of melatonin (M) per day was administered orally to four male white-tailed deer on a schedule that mimicked first decreasing and then increasing lengths of natural photoperiod. The following seasonal phenotypic and hormonal responses were observed: Pelage exchange, antler mineralization, velvet shedding, and rutting behavior of experimental animals were advanced by 50-55 days. Prolactin (PRL) levels exhibited a bimodal curve with peaks in May and August, as compared to a monomodal curve of controls (peak in June). Peak FSH levels of M-fed deer were advanced 2 months as compared to controls (June vs August). LH concentrations of both groups reached maxima in July; however, in the experimental group, LH levels declined much faster than in controls and then rose again in October-November. Testosterone (T) concentrations of M-fed bucks were elevated 2 months ahead of controls. Melatonin treatment had no significant effect on seasonal variation of T3, or T4. No seasonal rhythm of cortisol was seen in either group and no detectable effect of M was evident. No statistical differences in levels of alkaline phosphatase were seen between groups, although concentrations in experimental bucks sharply dropped to basal levels two months ahead of controls.
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PMID:The effect of orally administered melatonin on the seasonality of deer pelage exchange, antler development, LH, FSH, prolactin, testosterone, T3, T4, cortisol and alkaline phosphatase. 378 16

Prior studies have demonstrated that the pineal hormone, melatonin, can stimulate chloramphenicol acetyltransferase activity in Drosophila SL-3 cells transfected with a chloramphenicol acetyltransferase reporter construct containing the response element of rat bone sialoprotein (BSP). Based on these findings, studies were performed to determine whether melatonin could similarly modulate the expression of BSP in two cell lines, the MC3T3-E1(MC3T3) pre-osteoblast and rat osteoblast-like osteosarcoma 17/2.8 cell. Initial studies demonstrated that MC3T3 cells grown in the presence of 50 nM melatonin underwent cell differentiation and mineralization by day 12 instead of the 21-day period normally required for cells grown in untreated media. Melatonin increased gene expression of BSP and the other bone marker proteins, including alkaline phosphatase (ALP); osteopontin; secreted protein, acidic and rich in cysteine; and osteocalcin in MC3T3 cells in a concentration-dependent manner. Levels of melatonin as low as 10 nM were capable of stimulating transcription of these genes when cells were grown in the presence of beta-glycerophosphate and ascorbic acid. Under these conditions, melatonin induced gene expression of the bone marker proteins; however, this does not occur until the 5th day after seeding the culture dishes. Thereafter, MC3T3 cells responded to melatonin within 2 h of treatment. The fully differentiated rat osteoblast-like osteosarcoma 17/2.8 cells responded rapidly to melatonin and displayed an increase in the expression of BSP, ALP, and osteocalcin genes within 1 h of exposure to the hormone. To determine whether melatonin-induced osteoblast differentiation and bone formation are mediated via the transmembrane receptor, MC3T3 cells were treated in the presence and absence of melatonin with either luzindole, a competitive inhibitor of the binding of melatonin to the transmembrane receptors, or pertussis toxin, an uncoupler of G(i) from adenylate cyclase. Both luzindole and pertussis toxin were shown to reduce melatonin-induced expression of BSP and ALP. These results demonstrate, for the first time, that the pineal hormone, melatonin, is capable of promoting osteoblast differentiation and mineralization of matrix in culture and suggest that this hormone may play an essential role in regulating bone growth.
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PMID:Melatonin promotes osteoblast differentiation and bone formation. 1041 30

We evaluated the role of melatonin in endotoxemia caused by lipopolysaccharide (LPS) in unanesthetized rats. The expression of inducible isoform of nitric oxide synthase (iNOS) and the increase in the oxidative stress seem to be responsible for the failure of lungs, liver, and kidneys in endotoxemia. Bacterial LPS (10 mg/kg b. w) was i.v. injected 6 h before rats were killed and melatonin (10-60 mg/kg b.w.) was i.p. injected before and/or after LPS. Endotoxemia was associated with a significant rise in the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl-transferase, alkaline phosphatase, creatinine, urea, and uric acid, and hence liver and renal dysfunction. LPS also increased serum levels of cholesterol and triglycerides and reduced glucose levels. Melatonin administration counteracted these organ and metabolic alterations at doses ranging between 20 and 60 mg/kg b. w. Melatonin significantly decreased lung lipid peroxidation and counteracted the LPS-induced NO levels in lungs and liver. Our results also show an inhibition of iNOS activity in rat lungs by melatonin in a dose-dependent manner. Expression of iNOS mRNA in lungs and liver was significantly decreased by melatonin (60 mg/kg b. w., 58-65%). We conclude that melatonin inhibits NO production mainly by inhibition of iNOS expression. The inhibition of NO levels may account for the protection of the indoleamine against LPS-induced endotoxemia in rats.
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PMID:Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats. 1046 45

The pineal secretory product melatonin reportedly regulates release of growth hormone in humans and prevents phototherapy-induced hypocalcemia in newborn rats, suggesting that melatonin affects bone metabolism. Little is known about the effects of melatonin on bone in vitro or in vivo. The present study was undertaken to examine whether melatonin acts directly on normal human bone cells (HOB-M cells) and human osteoblastic cell line (SV-HFO cells) to affect osteogenic action in vitro. The effect of melatonin on bone cell proliferation was determined using the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carbo xanilide (XTT) assay after a 24 hr incubation with melatonin. Melatonin significantly and dose-dependently increased the proliferation in HOB-M cells and SV-HFO cells by 215 +/- 22.1%, and 193 +/- 6.4%), respectively, with a maximal effect at a concentration of 50 microM. To evaluate the effect of melatonin on bone cell differentiation, alkaline phosphatase (ALP) activity, osteocalcin secretion and procollagen type I c-peptide (PICP) production (a measure of type I collagen synthesis) were measured after a 48 hr treatment. While melatonin at micromolar concentrations did not significantly affect either the ALP activity or the osteocalcin secretion, it significantly and dose-dependently increased the PICP production in HOB-M cells and SV-HFO cells by 983 +/- 42.2%, and 139 +/- 4.2%, respectively, with the maximal stimulatory doses between 50 and 100 microM. These results provide new evidence that melatonin stimulates the proliferation and type I collagen synthesis in human bone cells in vitro, suggesting that melatonin may act to stimulate bone formation.
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PMID:Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. 1049 46

The aims of the present study were first to compare the effects of melatonin and vitamin E on the cholestasis syndrome and their protective effect on liver injury, and second, to evaluate the activity of antioxidant enzymes after treatment with these antioxidant drugs. Cholestasis was achieved in adult male Wistar rats by double ligature and section of the extra-hepatic biliary duct. Hepatic and plasma oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and reduced glutathione (GSH) in plasma and homogenates of hepatic tissue. Serum bilirubin, alkaline phosphatase (AP), and gamma-glutamyl-transpeptidase (GGT) were used to evaluate the severity of cholestasis, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Both vitamin E and melatonin were administrated 1 day before and 7 days after bile duct ligation. Acute ligation of the bile duct was accompanied by a significant increased in MDA and a decrease in GSH levels in both plasma and liver, as well as a significant reduction in antioxidant enzymes activities. The overall analysis of both treatments showed that melatonin (500 microg/kg daily) offered significantly better protection against cholestasis and a superior protective effect on hepatic injury than did vitamin E (15 mg/kg daily). Although vitamin E treatment resulted in a reduction of parameters of oxidative stress, the results were significantly better after a much lower daily dose of melatonin. Moreover, melatonin treatment was associated with a significant recovery of antioxidative enzymes. In conclusion, the present paper demonstrates a correlation between the intensity of biliary tract obstruction and increased free radical generation, as well as a direct correlation between the level of oxidative stress and the biochemical markers of liver injury. Melatonin (at a much lower dose than vitamin E) was much more efficient than vitamin E in reducing the negative parameters of cholestasis, the degree of oxidative stress and provided a significantly greater hepatoprotective effect against the liver injury secondary to the acute ligation of the biliary duct.
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PMID:Melatonin versus vitamin E as protective treatment against oxidative stress after extra-hepatic bile duct ligation in rats. 1155 69

The influence of melatonin administration to sperm donors on the freezability of ram semen and enzyme leakage through sperm cells during different steps of the cryopreservation process were evaluated in the breeding and non-breeding season. Melatonin implantation to rams in the breeding season improved post-thaw sperm viability and intact acrosome rates without influencing the motility rate (p < 0.05). Likewise, the post-thaw alkaline phosphatase release through sperm cells was significantly lower in the melatonin-treated group in comparison with untreated controls (p < 0.05). In the non-breeding season, melatonin administration enhanced intact acrosome rates (p < 0.05) and reduced aspartate aminotransferase activity (p < 0.05) post-thaw in the offseason ejaculates. Melatonin implantation twice in the breeding and non-breeding season did not produce any further improvement in the post-thaw sperm parameters in the non-breeding season ejaculates. It was concluded that melatonin administration to sperm donors improved freezability of ram semen collected from these rams and reduced enzyme leakage through sperm cells during cryopreservation.
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PMID:Effect of melatonin implantation to sperm donor rams on post-thaw viability and acrosomal integrity of sperm cells in the breeding and non-breeding season. 1155 72

The tropical parasite Schistosoma mansoni causes granulomatous inflammation after its eggs lodge in hepatic portal capillaries. In vitro studies indicate that the host's response involves the production of reactive oxygen species, although whether this occurs in vivo at the site of the infection is unknown. The role of oxidative processes in mice infected with S. mansoni was investigated in the current study using the antioxidant melatonin. In Experiment 1, the survival rate of infected mice with and without daily melatonin (10 mg/kg) administration was determined. After 56 d, 25 of 25 infected mice that were diluent treated had died. In contrast, 22 or 25 infected mice (88%) given melatonin were still alive at 56 d. Of these 22 surviving mice, melatonin injections were continued in 11 while the 11 others were switched to diluent. Within 10 d, 11 of 11 diluent-injected mice that were infected with S. mansoni were dead while 6 of 11 melatonin-treated mice survived. In Experiment 2, S. mansoni-infected mice were treated for 30 d with either melatonin or diluent. Uninfected, untreated mice served as controls. In these mice, the levels of lipid peroxidation (LPO) products, vitamin E, nitric oxide (NO), glutathione (GSH), and superoxide dismutase (SOD) activity in the liver, kidney, and spleen were measured. In the serum, cholesterol levels and liver damage (alkaline phosphatase (ALP), aspartate transaminases (AST), total protein, and albumin) were monitored. In addition, peroxynitrite anion (ONOO(-)) in the liver and kidney and inducible nitric oxide synthase (iNOS) in the spleen were immunocytochemically localized. Also, histopathological changes in the liver, kidney, and spleen were examined. The results documented increased LPO and NO levels and decreased vitamin E, GSH, and SOD activity in the liver, kidney, and spleen of S. mansoni-infected mice. Also, there was an increase in serum cholesterol and evidence of liver damage in the infected mice. Immunohistochemical results indicated positive staining of ONOO(-) in the liver and kidney and positive iNOS staining in the spleen of S. mansoni-infected mice. Histopathological observations revealed granuloma formation in the liver with eosinophil infiltration, a large number of megakaryocytes in the spleen, and degeneration with necrotic cells in some tubules of the kidney cortex in the infected mice. Melatonin administration after S. mansoni infection prevented most of the previously described changes. These results suggest that oxidative processes occur at the site of inflammation and are involved in the damaging effects of schistosomiasis and indicate that free radicals may be a major component of the disease. Likewise, melatonin, presumably due to its antioxidant and free radical scavenging activity, is highly protective against the pathological changes associated with schistosomiasis.
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PMID:Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni. 1184 22

To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 microg/mL water) and oestradiol (10 microg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual-energy X-ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham-operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy-induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham-operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter-regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues.
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PMID:Melatonin increases oestradiol-induced bone formation in ovariectomized rats. 1256 6

The ever-increasing understanding of oxygen radical-linked diseases, including the biological process of aging, has stimulated general interest in modulating these biological events. Melatonin has been reported to have antioxidant properties in addition to its known hormonal activities. However, reports on low-level chronic administration with its anti-aging influence are scanty. Hence, the present study was aimed to investigate the influence of low-dose chronic administration (0.10 mg/kg body weight/day for 3 months) of melatonin against age-induced oxidative stress in mice tissues, namely brain, liver, spleen and kidney. Sixteen-month-old mice were supplemented with melatonin (0.10 mg/kg body weight/day) for three months and then autopsied (at the age of 19 months) for the biochemical estimation of lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px) and serum phosphatase activity. Results indicate that age-induced augmentation (compared to 6-8-week-old mice) in the level of lipid peroxidation, GSSG and acid phosphatase is significantly (P < 0.001) ameliorated in melatonin-treated mice. Age-induced decline in the level of GSH, GSH-Px and alkaline phosphatase activity is inhibited significantly by the long-term administration of melatonin. The findings indicate that low-dose chronic administration of melatonin acts as a free radical scavenger and anti-aging agent.
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PMID:Melatonin-induced reduction in age-related accumulation of oxidative damage in mice. 1281 12

Melatonin was orally given to rats at the dosage of 0.75 mg/rat/day for 7 days and challenged on the day 7 with a single toxic dose of indomethacin (20 mg/kg, intramuscularly) to test either protection afforded by melatonin against indomethacin-induced oxidative tissue damage or effects of repeated administration of this hormone on some testicular metabolic parameters. The results showed increased lipid peroxidation, as evidenced by the formation of thiobarbituric acid reactive substances, accompanied by non-significantly decreased glutathione content in the testis of rats treated with indomethacin. However, prior administration of melatonin failed to prevent indomethacin-induced testicular lipid peroxidation. No change in the production of lipid peroxidation and glutathione was observed as well after treatment with melatonin alone. Meanwhile, exogenous melatonin inhibited testicular levels of total lipid, total protein, and activity of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. All treated rats exhibited unchanged activity of both acid phosphatase and lactate dehydrogenase. The results indicated inability of oral administration of melatonin to prevent some of the oxidative damaging effects of indomethacin in the rat testis. In addition, the study provided an evidence that melatonin has an inhibitory action on the testicular metabolism in adult rats and thereby suggests a possible role of this hormone in modulating functions of rat testis.
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PMID:Melatonin produced metabolic changes in testis and did not prevent indomethacin-induced testicular lipid peroxidation in adult rat. 1526 51


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