Assessment of metabolic responses following silica nanoparticles in zebrafish models using 1H NMR analysis.

Silica nanoparticles (SNPs) are widely explored as drug carriers, gene delivery vehicles, and as nanoparticles intended for bone and tissue engineering. SNPs are highly evident through various clinical trials for a wide range of biomedical applications. SNPs are biocompatible and promising nanoparticles for next-generation therapeutics. However, despite the well-established importance of SNPs, metabolomics methods for the SNPs remain elusive which renders its maximal clinical translation. We applied 1H nuclear magnetic resonance (1H NMR) spectroscopy to investigate the metabolomics profile in Zebrafish (Danio rerio) exposed to SNPs. Zebrafish were exposed to the SNPs (10.0, 25.0, and 50.0 µg/mL) for 72 h and whole-body samples were subjected for targeted profiling. Pattern recognition of 1H NMR spectral data depicted alterations in the metabolomic profiles between control and SNPs exposed zebrafish. We found that tryptophane, lysine, methionine, phenylalanine, tyrosine, sn-glycero-3-phosphocholine (G3PC), and o-phosphocholine were decreased. The metabolic expression of niacinamide, nicotinamide adenine dinucleotide (NAD+), citrate, adenosine triphosphate (ATP), and xanthine were increased in zebrafish with SNPs treatment. We are report for the first time on metabolite alterations and phenotypic expression in zebrafish via 1H NMR. These results demonstrate that SNPs can adversely affect the significant metabolic pathways involved in energy, amino acids, cellular membrane, lipids, and fatty acid metabolisms. Metabolomics profiling may be able to detect metabolic dysregulation in SNPs-treated zebrafish and establish a foundation for further toxicological studies.

In silico analysis of selected nutrition rich fruit of Bunch berry (Lantana camara) constituents as human acetylcholinesterase (hAchE), carbonic anhydrase II (hCA-II) and carboxylesterase 1 (hCES-1) inhibitory agents.

Background: Bunch berry (Lantana camara) is primarily composed of flavonoids and vitamin C; therefore, it has been shown to possess various medical characteristics, including the ability to relieve fever, inflammation, and urinary tract infections. Objective: In this study, we intended to assess twenty chosen constituents of Bunch berry as potent inhibitory agents of human acetylcholinesterase (hAchE), carbonic anhydrase II (hCA-II) and carboxylesterase 1 (hCES-1) employing in silico techniques. Methods: The twenty chosen Bunch berry components were examined about docking behaviour of hAchE, hCA-II and hCES-I by using the Swissdock method. Apart from to docking, Molecular physico-chemical, drug-likeness, ADME (ingesting, dispersing, metabolising, and excreting), and toxicity assessments were also performed utilising the Molinspiration, Swiss ADME, pkCSM, and STITCH web sites, correspondingly. Results: Eight ligands (40 %) have exhibited strict adherence to Lipinski's rule of five (Ro5), according to molecular physico-chemical study. Drug-likeness property analysis has shown that five ligands (25 %) of Bunch berry predicted to exhibit moderate bioactivity score against all the descriptors. ADME analysis has shown that five ligands (25 %) of Bunch berry are predicted to possess high gastrointestinal absorption property Toxicity analysis has shown that six ligands (30 %) of Bunch berry are predicted to have hERG II (Human ether-a-go-go-related gene) inhibition activity. According to the docking analysis, lantic acid has the lowest atomic binding energy for all three target enzymes, hAchE (-6.23 kcal/mol), hCA-II (-4.46 kcal/mol), and hCES-I (-5.99 kcal/mol), respectively. Conclusions: Thus the current find provides an advanced understanding the twenty selected ligands of Bunch berry as potent inhibitory agents of human acetylcholinesterase (hAchE), carbonic anhydrase II (hCA-II) and carboxylesterase 1 (hCES-1).

Evaluation of Developmental Toxicity and Oxidative Stress Caused by Zinc Oxide Nanoparticles in Zebra Fish Embryos/ Larvae.

Zinc oxide nanoparticles (ZnO NPs) are used in various fields, including biological ones. ZnO NPs are eventually disposed of in the environment where they may affect natural systems, and there is no international law to regulate their manufacture, usage, and disposal. Hence, this present study is carried out to synthesise a more non-toxic and bioactive ZnO NPs from the marine algae Sargassum polycystum. The ZnO NPs were biologically produced using the marine algae Sargassum polycystum. The dynamic light scattering result describes that synthesised particles' average size is about 100 nm in diameter. Transmission electron microscopy (TEM) analysis demonstrated the rod-like morphology of ZnO NPs. Fourier tranform-infrared spectroscopy (FT-IR) results revealed the presence of functional groups in ZnO NPs. The selected area electron diffraction (SAED) results strongly suggested the ZnO NPs crystallinity. ZnO NPs surface morphology and compositions were identified by scanning electron microscopy (SEM- EDX) values. To analyse the toxicity of synthesised nanoparticles, zebra fish larvae were used, which involved subjecting embryos to various ZnO NPs concentrations at 1 hpf and analysing the results at 96 hpf. The 60 and 80 ppm sub-lethal doses were chosen for further studies based on the LC50 (82.23 ppm). In the ZnO NPs-treated groups, a significant slowdown in pulse rate and a delay in hatching were seen, both of which impacted the embryonic processes. A teratogenic study revealed a dose-dependent increase in the incidence of developmental deformities in the treated groups. Along with increased oxidants and a corresponding reduction in antioxidant enzymes, Na+ K+-ATPase and AChE activity changes were seen in ZnO NPs-treated zebra fish larvae groups. The apoptosis process was increased in ZnO NPs-treated groups revealed by acridine orange staining. These results indicate that the green synthesis process cannot mitigate the oxidative stress induced by ZnO NPs on oxidative signalling.

Pouteria caimito fruit derived nanoparticles inhibited the apple ring rot disease as well as extended the shelf-life of sliced apples.

Background: Apple disease, exaggerated by Botryosphaeria dothidea, is a foremost intimidating problem for extending the apple fruit shelf-life and producing substantial economic losses for cultivators and distributors. Alternate sources are urgently needed to prevent or inhibit the ring rot infection of apple fruit instigated by Botryosphaeria dothidea. Objective: In this current study, we premeditated to make novel organic nanoparticles as of Pouteria caimito fruit extract and calcium chloride (PCNP), which were used to evaluate the preventive outcome of Botryosphaeria dothidea-caused apple disease on postharvest apple fruits. Results: Our findings corroborated that the fruit derived nanoparticle had been confirmed for quality and size by altered estimations such as fourier transform infrared (FTIR), UV-vis spectroscopic analysis, scanning electron microscope and energy dispersive X-ray (SEM and EDX) estimation, and dynamic light scattering (DLS) analysis. In addition, we have investigated the excellent inhibitory action of the pathogen infection in apples initiated by Botryosphaeria dothidea. The protective enzymes function was pointedly improved in nanoparticle-treated apple fruits once equated with those of control apple fruits. The catalase (CAT) and superoxide dismutase (SOD) activities were pointedly improved in nanoparticle-treated fruits when compared to those of control fruits. The shelf-life extension studies were conducted for 7 days with a fresh-cut apple. The total soluble solid, pH, weight loss, and sensory studies were analyzed, and they proved the extension of sliced apple shelf life up to 7 days. Conclusions: The discoveries of this study provided a well-organized, harmless, and environment-friendly substitute to control the apple disease as well as the durability postponement of sliced apples 7 days or may longer.

Vitamin A- and C-rich Pouteria camito fruit derived superparamagnetic nanoparticles synthesis, characterization, and their cytotoxicity.

Background: Recently, green nanoparticles are gaining importance in drug development because of their lower toxicity, sustainability, cost effectiveness, simplicity, and ecofriendly nature compared with toxic chemicals. Objective: In this study, we developed a nontoxic method for synthesizing iron oxide nanoparticles by using the fruit of Pouteria caimito that is rich in vitamin A and C and evaluated their cytotoxicity. Methods: Pouteria caimito fruit¬-derived superparamagnetic nanoparticles (PCSNs) were characterized using physical and chemical methods, and their cytotoxicity was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. Results: Ultraviolet-visible spectroscopy (UV-Vis spectro) analysis of PSNs showed a peak at 277 nm. Transmission electron microscopy (TEM) findings showed that PSNs exhibited a nanorod shape with their sizes ranging from 9.41 nm to 16.96 nm (average size: 13.08 nm). The findings of dynamic light scattering (DLS) indicated that the particle size was 186. 6-847.3 d.nm with an average of 367.5 d.nm. The Zeta potential analysis indicated that PSNs exhibited uniform surface charge distribution, and their surface charge was equal to -13.7 mV. Fourier-transform infrared spectroscopy (FTIR) analysis showed that PSNs exhibited bands at 3412, 1629, 1384, 1075, 818, 697, and 471 cm-1. Energy-dispersive X-ray spectroscopy (EDX) results showed that iron was the major element present in PCSNs, followed by other biomolecules such as C, O, and Cl, indicating the production of iron oxide nanoparticles. Conclusion: The Pouteria caimito fruit that possesses strong oxidizing and nontoxic properties can be a potentially attractive source for the production of iron oxide nanoparticles. Moreover, the cytotoxicity assay results revealed that iron oxide nanoparticles synthesized using the Pouteria caimito fruit extract derived can be used for targeting cancer cells and treating other diseases because of their nontoxic nature. These nanoparticles can be used for the treatment of cancer and other diseases in the future.

Cassia fistula nutrition rich flower tea derived biotic nanoparticles synthesis, characterization and their antioxidant and anti-hyperglycaemic properties.

Background: Cassia fistula (CF) is a nutrient-rich flowering plant and it has been used to cure numerous human health problems including cardiac diseases, bacterial infection, and inflammation. Objective: The purpose of this study was to investigate the production and characterisation of biomimetic iron oxide nanoparticles (ICF) derived from CF flower tea as well as evaluate their antioxidant and anti-hyperglycemic properties. Methodology: CF tea derived ICF synthesis and characterized by established physical-chemical methods. Moreover, this synthesized ICF were checked for their antioxidant and anti-hyperglycemic properties such as alpha-amylase, glucose intake, total antioxidant (TAA), ferrous reducing (FA), and radical scavenging (DPPH) properties. Results: The synthesized ICF characterization and size were confirmed primarily by described physical and chemical methods. Our findings revealed that ICF have a powerful antihyperglycemic mechanism by involving alpha-amylase inhibition and enhanced glucose absorption. Meanwhile, this ICF exhibited distinguished antioxidant competence by improving TAA and free radical scavenging (TAA, DPPH) properties. Finally, this ICF has proven anti-hyperglycemic and antioxidant mechanisms due to their presence of nano-sized biomolecules. Conclusion: In this study, it might be concluded that the CF is the best source for iron oxide nanoparticles production with clarity, small size and high solidity. Moreover, this nanoparticle has proven in vitro anti-hyperglycemic and antioxidant mechanisms.

A child with refractory orbital cellulitis after water pipe smoking.

Orbital cellulitis in children rarely occurs secondary to smoking water pipe. A 3-year-old girl who presented with fever, eyelid swelling, pain, and proptosis of the left eye for 4 days after water pipe consumption. The patient was given the usual course of antibiotics for a few days along with subperiosteal abscess drainage however no improvement was noticed for a week. Cultures were positive for methicillin-resistant Staphylococcus aureus and pseudomonas aeruginosa. Intravenous dexamethasone was co-administered in three courses for 3 weeks, during which residual symptoms was slowly resolving. In conclusion, attempt of dexamethasone in children can shorten hospital stay and augment full recovery.

Galangin controls streptozotocin-caused glucose homeostasis and reverses glycolytic and gluconeogenic enzyme changes in rats.

Galangin is a natural compound with anticancer, anti-inflammatory, and antioxidant properties. However, the ameliorating effect of streptozotocin (STZ)-induced glucose homeostasis has not yet been evaluated. Hence, this study was aimed at exploring the role of galangin in STZ-induced glucose homeostasis, glycolytic and gluconeogenic enzyme changes in rats. STZ-treated rats were characterised by increased plasma glucose and glycosylated haemoglobin and decreased plasma insulin and haemoglobin compared with the normal cage. Administration of galangin to STZ-treated rats effectively reversed the adverse biochemical and haematological changes. Significant alterations in glycogen levels as well as glycolytic and gluconeogenic enzyme activities were witnessed in STZ-treated rats, and these changes were reversed upon treatment with galangin. The compound exerts potent anti-hyperglycemic effects by regulating the glucose homeostasis and reversing the glycolytic and gluconeogenic enzyme changes in rats. However, the exact mechanism through which galangin prevents diabetic complications needs to be studied in detail.

Lavatera critica controls systemic insulin resistance by ameliorating adipose tissue inflammation and oxidative stress using bioactive compounds identified by GC-MS.

BACKGROUND: Lavatera critica, a leafy green herb, is reported to have many pharmacological activities; but, the improvement of insulin sensitivity against the high gram-fat diet (HGFD)-caused insulin resistance (IR) has not yet been studied. OBJECTIVE: This study evaluated the role of Lavatera critica leaf extract (LCE) in systemic insulin resistance through the alleviation of adipose tissue inflammation and oxidative damage in HGFD fed mice. METHODS: The mice were fed with HGFD for 10 weeks and the diet was supplemented with LCE each day for the next five weeks. Body weight, food intake, leptin, blood glucose, insulin, insulin resistance, and pro- and anti-inflammatory genes expression were assessed on day 106. RESULTS: The HGFD control mice displayed markedly elevated adipose tissue inflammation, oxidative stress, insulin inactivity, and hyperglycemia. Administration of LCE in the HGFD mice, especially a dose of 100 mg/kg, lowered the body weight, food intake, plasma leptin, plasma glucose, plasma insulin, insulin resistance, and increased the food efficacy ratio when compared with the HGFD control mice. The oral glucose tolerance test (OGTT) revealed that LCE prevented further increase in the circulating levels after the glucose load. LCE-treated mice demonstrated a marked suppression of pro-inflammatory cytokines mRNA expression. On the other hand, the mice showed a higher anti-inflammatory genes mRNA expression in the adipose tissue. In addition, LCE treatment improved the oxidative damage as evidenced by the reduced levels of lipid hydroperoxides and thiobarbituric acid reactive substances coupled with the increased antioxidants (superoxide dismutase, total glutathione, glutathione/glutathione disulfide ratio and glutathione peroxidase) in the adipose tissue, plasma and erythrocytes. Gas chromatography-mass spectrometry analysis of the bioactive compounds revealed the presence of 9, 12, 15-octadecatrienoic acid, vitamin E, phytol, hexadecanoic acid, benzenepropanoic acid, and stigmasterol. CONCLUSIONS: These findings prove that LCE improves the insulin-sensitizing activity in the mouse model of HGFD-caused IR, probably due to the amelioration of adipose tissue inflammation and oxidative damage. Hence, the LCE could serve as a useful anti-diabetic agent.

Galangin, a dietary flavonoid, ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia.

CONTEXT: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known. OBJECTIVE: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia. MATERIALS AND METHODS: Diabetes was induced in adult Wistar rats by administering 40 mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320 mg/kg. Therefore three doses of galangin (4, 8 or 16 mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days. RESULTS: Diabetic rats showed a significant (p < 0.05) increased levels of plasma glucose (281.10 mg/dL) and decreased levels of insulin (6.01 µU/mL). Additionally, diabetic rats showed a significant (p < 0.05) increased levels of plasma lipid profiles such as total cholesterol (149.05 mg/dL), triglycerides (143.28 mg/dL), free fatty acids (139.37 mg/dL), phospholipids (127.53 mg/dL), plasma low-density lipoprotein-cholesterol (98.72 mg/dL), plasma very low-density lipoprotein-cholesterol (28.65 mg/dL), and significant (p < 0.05) decreased in plasma high-density lipoprotein-cholesterol (21.68 mg/dL). When galangin was administered to the hyperglycaemic rats, plasma glucose and insulin levels and lipid profiles reverted to levels similar to those in healthy control rats. DISCUSSION AND CONCLUSIONS: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.

Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced insulin resistance and lipid accumulation through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes.

Healthy plants and their constituents have been considered as a safe remedy for the treatment of obesity and obesity associated diseases. Herbacetin is a dietary flavonoid that has been explored for many pharmacological activities; but, the anti-hyperglycaemic and anti-hyperlipidemic properties of herbacetin have not yet been explored. The present study was performed to evaluate the ameliorative effect of herbacetin on high-fat diet-induced hyperglycaemia and hyperlipidemia in 57BL/6 J mice. Obesity associated insulin resistance was induced by continuously feeding the mice with high-fat diet for 10 weeks. Afterwards, mice were subjected to intragastric administration of herbacetin (different doses) daily along with high-fat diet for the next 5 weeks. At the end of 106th day, changes in body weight, blood glucose, insulin, HOMA-IR, and lipids profiles and lipid-regulating enzymes were evaluated. Herbacetin significantly reduced the body weight, plasma glucose, plasma insulin, and HOMA-IR activity in obesity associated insulin resistant mice (OIR). In addition, herbacetin administration significantly reduced the plasma and hepatic total cholesterol, triglycerides, and free fatty acids in OIR mice. Moreover, herbacetin significantly improved the altered hepatic lipid metabolizing and lipid-regulating enzymes such as SREBP-1c, and 2, fatty acid synthase (FAS), fatty acid ß-oxidation (ß-oxidation), malic enzyme, glucose 6-phosphate dehydrogenase (G6PD), and carnitine palmitoyltransferase (CPT) when compared to OIR control mice. Histopathological examination clearly showed that herbacetin decreases lipid droplets in the liver tissue. Thus, observed results strongly indicate that herbacetin provides remarkable protection against the harmful effects of chronic high-fat diet consumption because of its anti-hyperglycaemic and anti-hyperlipidemic properties through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes.

Galangin, a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats.

OBJECTIVE: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. METHODS: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg-1 body weight (BW)). Galangin (8 mg kg-1 BW) or glibenclamide (600 µg kg-1 BW) was given orally daily once for 45 days to both healthy and diabetic rats. RESULTS: Diabetic rats showed significant (P < 0.05) increase in liver mitochondrial oxidant [Thiobarbituric acid reactive substance (TBARS)] level and a significant decrease in enzymatic [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and non-enzymatic (reduced glutathione (GSH)) antioxidant levels when compared with healthy rats. The mitochondrial enzymes isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) and mitochondrial respiratory chain enzymes NADH-dehydrogenase and Cytochrome c-oxidase were decreased significantly (P < 0.05) in diabetic rats when compared with healthy rats. A natural flavonoid galangin administered to hyperglycemia-induced rats resulted in the following findings as compared to hyperglycemia-induced control rats: the oxidant levels decreased significantly (P < 0.05); the enzymatic and non-enzymatic antioxidant levels increased significantly (P < 0.05) and the function of mitochondrial enzymes and the mitochondrial respiratory chain enzymes increased significantly (P < 0.05). CONCLUSION: From the results, we conclude that galangin could maintain liver mitochondrial function in diabetic rats.

Lavatera critica, a green leafy vegetable, controls high fat diet induced hepatic lipid accumulation and oxidative stress through the regulation of lipogenesis and lipolysis genes.

BACKGROUND: Lipid accumulation is the most vital risk factor for inducing nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Thus, the development of novel drugs is urgently needed to control obesity related diseases. OBJECTIVE: Here, we investigated the protective role of Lavatera critica (LC), a green vegetable, in male C57BL/6J mice fed with high fat (HF) diet for 10 weeks to induce hepatic lipid accumulation and oxidative cellular damage. RESULTS: After oral administration of chloroform (CFLC), ethyl acetate (EFLC), or methanol (MFLC) fractions of Lavatera critica to the HF group, EALC alone significantly reduced the activities of hepatic markers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST); moreover, the results showed that 50 mg/kg dose has the maximum activity. Thus, this active dose of EFLC was used for further analysis. Moreover, EFLC reduced the level of hepatic triglycerides (TG), total cholesterol (TC), free fatty acids (FFA), and prevented further increase in the body weight. Intriguingly, EFLC treatment also reversed the mRNA expression of fatty acid oxidative genes, such as peroxisome proliferator activated receptor-α (PPAR-α), carnitine palmitoyltransferase-1 (CPT-1), and acetyl-CoA carboxylase (ACO), and fatty acid synthesis genes such as fatty acid synthase (FAS), sterol-regulatory-element-binding protein-1c (SREBP-1c), and acetyl-CoA carboxylase (ACC). Furthermore, EFLC treatment also decreased the production of oxidative stress biomarkers, such as conjugated diene (CD), thiobarbituric acid reactive substances (TBARS), and lipid hydroperoxide (LOOH), and significantly enhanced the level of enzymatic antioxidants, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as non-enzymatic antioxidants, such as reduced glutathione (GSH), vitamin C, and vitamin E in the liver. CONCLUSION: Taken together, we conclude that EFLC has a protective effect against HF diet induced hepatic lipid accumulation and oxidative cellular damage through the regulation of lipogenesis and lipolysis genes.

Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats.

OBJECTIVE: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced by intraperitoneal administration of low-dose STZ (40 mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8 mg/kg BW) or glibenclamide (600 µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats. RESULTS: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide. CONCLUSION: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.

Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats.

CONTEXT: Kaempferol is a flavonoid found in many edible plants (e.g. tea, cabbage, beans, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine. Numerous preclinical studies have shown that kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, and antidiabetic activities. OBJECTIVE: The present study investigates the effect of kaempferol on membrane-bound ATPases in erythrocytes and in liver, kidney, and heart of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced into adult male albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 d to normal and STZ-induced diabetic rats. The effects of kaempferol on membrane-bound ATPases (total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase) activity in erythrocytes and in liver, kidney, and heart were determined. RESULTS: In our study, diabetic rats had significantly (p < 0.05) decreased activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase in erythrocytes and tissues. Oral administration of kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) for a period of 45 d resulted in significant (p < 0.05) reversal of these enzymes' activities to near normal in erythrocytes and tissues when compared with diabetic control rats. DISCUSSION AND CONCLUSION: Thus, obtained results indicate that administration of kaempferol has the potential to restore deranged activity of membrane-bound ATPases in STZ-induced diabetic rats. Further detailed investigation is necessary to discover kaempferol's action mechanism.

Effect of weight loss on serum osteocalcin and its association with serum adipokines.

Studies have suggested that osteocalcin, a bone formation marker, is related to body metabolism and insulin sensitivity. Whether this relation is mediated through an interaction with adipokines remains unclear. The aim of this study was to assess the effect of weight loss on serum osteocalcin and its relation with three adipokines, adiponectin, chemerin, and resistin. Forty-nine obese nondiabetic males completed a four-month dietary program. Body mass index (BMI) decreased significantly from 39.7 ± 7.6 to 37.8 ± 7.6 (P < 0.001). This was associated with significant reduction in waist circumference, fasting blood glucose, HOMA-IR, total and LDL-cholesterol, bone-specific alkaline phosphatase (BAP), and resistin (P < 0.05). There was significant increase in serum adiponectin and undercarboxylated osteocalcin (uOC) (P < 0.001). The changes in uOC levels were negatively correlated with changes in serum triglycerides (r = -0.51, P < 0.001) and positively correlated with changes in BAP (r = 0.52, P < 0.001). In contrast, the changes in uOC were not correlated with changes in BMI, waist circumference, fasting blood glucose, HOMA-IR, total and LDL-cholesterol, hsCRP, vitamin D, and circulating adipokines. We concluded that the increase in serum uOC following weight loss is not related to the changes in circulating adipokines levels.

Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats.

OBJECTIVE: The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats. RESULTS: The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal. CONCLUSION: The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.

Morin, a flavonoid, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats.

BACKGROUND: Myocardial infarction affects a large population in the world. Lipid peroxide metabolism plays an important role in the pathology of myocardial infarction. OBJECTIVE: The present study was designed to investigate the antioxidant potential of morin, a flavonoid in isoproterenol (ISO)-induced myocardial infarction (MI), in rats. MATERIALS AND METHODS: Male albino Wistar rats were pre-treated with morin (40 mg/kg), daily for a period of 30 days. After the treatment period, ISO (85 mg/kg), was subcutaneously injected in rats at an interval of 24 h for 2 days. RESULTS: ISO-administered rats showed elevated levels of thiobarbituric acid reactive substances (TBARS), and lipid hydro-peroxide (LOOH), in plasma and heart. Pretreatment with morin, the above changes were significantly reduced to near normal level. ISO-administered rats showed decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in heart. In addition, decrease the levels non enzymatic antioxidants such as reduced glutathione (GSH), vitamin C and vitamin E in plasma and heart while ceruloplasmin in plasma. CONCLUSION: Pretreatment with morin, reversed these above biochemical changes towards normalcy. These findings revealed that, the morin possess antioxidant activity in experimentally induced cardiac toxicity.

Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells.

Silica (E551) is commonly used as an anti-caking agent in food products. The morphology and the dimension of the added silica particles are not, however, usually stated on the food product label. The food industry has adapted nanotechnology using engineered nanoparticles to improve the quality of their products. However, there has been increased debate regarding the health and safety concerns related to the use of engineered nanoparticles in consumer products. In this study, we investigated the morphology and dimensions of silica (E551) particles in food. The silica content of commercial food products was determined using inductively coupled plasma optical emission spectrometry. The result indicates that 2.74-14. 45 µg/g silica was found in commercial food products; however, the daily dietary intake in increase causes adverse effects on human health. E551 was isolated from food products and the morphology, particle size, crystalline nature, and purity of the silica particles were analyzed using XRD, FTIR, TEM, EDX and DLS. The results of these analyses confirmed the presence of spherical silica nanoparticles (of amorphous nature) in food, approximately 10-50 nm in size. The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied. The results suggest that E551 induces a dose-dependent cytotoxicity and changes in ROS levels and alters the gene expression and cell cycle. Treatment with a high concentration of E551 caused significant cytotoxic effects on WI-38 cells. These findings have implications for the use of these nanoparticles in the food industry.

Evaluation and identification of damaged single nucleotide polymorphisms in COL1A1 gene involved in osteoporosis.

INTRODUCTION: Single-nucleotide polymorphisms (SNPs) are biomarkers for exploring the genetic basis of many complex human diseases. The prediction of SNPs is promising in modern genetic analysis but it is still a great challenge to identify the functional SNPs in a disease-related gene. The computational approach has overcome this challenge and an increase in the successful rate of genetic association studies and reduced cost of genotyping have been achieved. The objective of this study is to identify deleterious non-synonymous SNPs (nsSNPs) associated with the COL1A1 gene. MATERIAL AND METHODS: The SNPs were retrieved from the Single Nucleotide Polymorphism Database (dbSNP). Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on proteins were predicted by PolyPhen and SIFT respectively. FASTSNP was used for estimation of risk score. RESULTS: Our analysis revealed 247 SNPs as non-synonymous, out of which 5 nsSNPs were found to be least stable by I-Mutant 2.0 with a DDG value of > -1.0. Four nsSNPs, namely rs17853657, rs17857117, rs57377812 and rs1059454, showed a highly deleterious tolerance index score of 0.00 with a change in their physicochemical properties by the SIFT server. Seven nsSNPs, namely rs1059454, rs8179178, rs17853657, rs17857117, rs72656340, rs72656344 and rs72656351, were found to be probably damaging with a PSIC score difference between 2.0 and 3.5 by the PolyPhen server. Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, were found to be highly polymorphic with a risk score of 3-4 with a possible effect of non-conservative change and splicing regulation by FASTSNP. CONCLUSIONS: Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, are potential functional polymorphisms that are likely to have a functional impact on the COL1A1 gene.