Oligochaeta ramosa (Roxb.) Extract Regulates Lipid Metabolism and Exerts Hepatoprotective Effects in Cadmium-Induced Hepatic Injury in Rats.

Environmental pollutants present a potential source of toxicity when exposed to humans. The study was aimed at investigating the potential of Oligochaeta ramosa (Roxb.) as a hepatoprotective agent in cadmium-induced hepatotoxicity causing lipid profile disturbance. The aqueous methanolic (30 : 70 v/v) extract of O. ramosa Roxb. (AME.Or) was subjected to preliminary phytochemical analysis, whereas the antioxidant activity of its constituents was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The hepatoprotective and antihyperlipidemic effects of AME.Or was investigated by dividing animals into five groups (A-E). Animals were either treated with normal saline or CdCl2 (6.5 mg/kg, intraperitoneally) followed by treatment with silymarin (100 mg/kg), or AME.Or (200 mg/kg) and AME.Or (400 mg/kg) for consecutive three weeks. Blood samples were collected, and the serum lipid profile was assessed on the 11th and 21st day of treatment. Histopathological analysis was performed after euthanization. In vitro analysis of AME.Or revealed 64% inhibition as free radicals scavenging potential during DPPH, total phenolic content (TPC) (79.92 mgGAE/g), and total flavonoids content (TFC) (38.75 mgRE/g). The group intoxicated with CdCl2 showed significantly high (p ≤ 0.05) levels of the liver function indicators and lipid profile than in the control group. The higher dose of AME.Or (400 mg/kg) significantly decreased the aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin (p ≤ 0.001), decreased total cholesterol and triglycerides (p ≤ 0.01) while significantly increased high density lipoprotein (HDL; p ≤ 0.01) as compared to the intoxicated group. The histopathological analysis of the liver revealed signs of necrosis in the intoxicated group, while AME.Or treated groups showed marked improvement. The findings accentuate the therapeutic importance of O. ramosa (Roxb.) as a hepatoprotective remedy.

Ficus carica and Sizigium cumini Regulate Glucose and Lipid Parameters in High-Fat Diet and Streptozocin-Induced Rats.

Obesity linked diabetes, popularly known as diabesity, has been viewed as a direct product of the modern lifestyle in both developed and developing countries, and its increased prevalence is seen as a major threat to public health globally. Ficus carica (FC) and Syzigium cumini (SC) are part of indigenous flora with traditional medicinal properties. Fresh seeds of SC fruit and fruit of FC were collected and macerated to obtain the final extract. Wistar rats were divided into seven groups fed either on a normal diet or high-fat diet (HFD) along with streptozocin (STZ) to induce diabesity. The crude extract of FC (FC.Cr.) and SC (SC.Cr.) were administered at 250 mg/kg/day and 500 mg/kg/day in induced diabesity state. Body weights, blood glucose level, complete blood count (CBC), cholesterol, triglycerides (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were recorded to analyze their effects on glucose and lipid metabolism. Further, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured to examine their effects on lipid peroxidation and ant oxidative enzyme. Results showed that both FC.Cr. and SC.Cr. have the potential to control obesity-linked type 2 diabetes mellitus (T2DM) by lowering the body weights, serum glucose, cholesterol, TG, LDL, and VLDL, while increasing the protective effects of HDL dose-dependently. The crude extract of both plants showed significant activity to raise SOD and curb MDA under diabetic states. It was concluded that both FC.Cr. and SC.Cr. exhibited remarkable therapeutics potential in HFD-STZ-induced diabetic rats. However, we found that the effects of SC.Cr. are relatively more pronounced as compared to FC.Cr. in almost all parameters.

Cuscuta reflexa Roxb. Expedites the Healing Process in Contact Frostbite.

Frostbite is caused due to extreme vulnerability to cold, resulting in damage of deeper and superficial tissues alike. In this study, we report the anti-inflammatory and wound-healing properties of aqueous methanolic extract of Cuscuta reflexa (Cs.Cr) against contact frostbite. Thirty rats were divided into five groups including three treatment groups with increasing doses of Cs.Cr, a standard drug group receiving acetylsalicylic acid (ASA), and a metal bar-induced frostbite group. Frostbite injury was induced by a 3 × 3.5 cm metal bar frozen up to -79°C on shaved skin for continuous 3 minutes. Wounded area percentages were recorded to measure the healing rate in response to Cs.Cr administration. Haematological parameters and malondialdehyde content were also noted. On treatment with Cs.Cr, the healing rate is drastically increased and lipid peroxidation product malondialdehyde was decreased in a dose-dependent manner. Results were compared with frostbite and ASA (standard drug group). These results indicate that Cs.Cr possesses excellent wound-healing properties against frostbite injury and can prove to be a prospective compound in such conditions.

In Silico Prediction of the Mode of Action of Viola odorata in Diabetes.

BACKGROUND: The metabolic syndrome increases the risk of different diseases such as type 2 diabetes. The prevalence of metabolic syndrome has rapidly grown and affected more than 230 million people worldwide. Viola odorata is a traditionally used plant for the treatment of diabetes; however, its mechanism to manage diabetes is still unknown. PURPOSE: This study was designed to systematically assess the mechanism of action of Viola odorata in diabetes. METHODS: An extensive literature search was made to establish an ingredient-target database of Viola odorata. Of these, targets related to diabetes were identified and used to develop a protein-protein interaction network (PPIN) by utilizing the STITCH database. The obtained PPIN was assessed through Gene Ontology (GO) enrichment analysis based on ClueGO plugin. RESULTS: According to the acquired data, there were about 143 chemical constituents present in Viola odorata having 119 protein targets. Of these, 31 targets were established to give the pharmacological effect against diabetes. The UniProt database was used for screening of 31 targets, out of which Homo sapiens contained 22 targets. Ultimately, 207 GO terms, grouped into 41 clusters, were found by gene analysis, and most of them were found to be linked with diabetes. According to findings, several proteins including TP53, BCL2, CDKN1A, 1L6, CCND1, CDKN2A, and RB1 have a significant role in the treatment of diabetes by Viola odorata. CONCLUSION: The possible activity of Viola odorata in the management of diabetes may be mediated by several molecular mechanisms, including the glutamine metabolic process, IRE1-mediated unfolded protein response, and pentose metabolic process.

Berberis lycium Royle. extracts attenuate inflammation and modulates hyperglycemia in alloxan induced diabetic rats.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity.

We aimed to study the effects of Citrus aurantium (C. aurantium) on renal functions in cisplatin-induced nephrotoxicity in rats. The study involved male Wistar rats weighing 250-300 g that were fed and kept under standard conditions. Rats were randomly divided into control, cisplatin administered, C. aurantium 200 mg/kg, and C. aurantium 400 mg/kg groups. Cisplatin was administered at 5 mg/kg i.p. once at the start of study to induce nephrotoxicity. Blood and urine samples were obtained at alternative days for analysis. The body weight and urine output were monitored at regular intervals. Plasma and urinary sodium, potassium, and creatinine levels were measured at the end of study duration. Absolute excretion of sodium and potassium; sodium to potassium ratio; kidney weights; fractional excretion of sodium and potassium; and absolute creatinine clearance were determined to analyze the effects of C. aurantium. Histopathological changes of kidney tissues were studied to determine relevant effects. The results indicate that cisplatin lowered the total body weights while raising the urinary output and kidney weights, reversed by C. aurantium both dose and time dependently. Similarly, C. aurantium markedly normalized plasma, urinary sodium, potassium, and creatinine levels. Cisplatin-induced absolute sodium clearance, absolute potassium clearance, absolute creatinine clearance, sodium to potassium ratio, and fractional excretion of sodium and potassium were significantly reversed by C. aurantium. Histopathological analysis showed notable improvement in C. aurantium administered groups as compared to cisplatin-induced group. Study suggests that C. aurantium possesses excellent nephroprotective effects against cisplatin-induced toxicity.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

ß-Elemene attenuates atherosclerosis in apolipoprotein E-deficient mice via restoring NO levels and alleviating oxidative stress.

ß-Elemene is a major bioactive sesquiterpenoids compound isolated from the essential oils of Curcuma Wenyujin, a Chinese medicinal herb that treats tumor in clinics. However anti-atherosclerotic effects of ß-elemene have not been fully investigated in vivo. The objective of this study is to further elucidate the anti-atherosclerotic activities of ß-elemene in ApoE-/- mice. Staining techniques and immunohistochemistry were used to validate atherosclerosis. Serum lipids, plasma nitrite and nitrate were analyzed by colorometric methods. ROS and antioxidative enzymes were measured through kits. Proteome profiler array was performed to analyze atherosclerosis-related inflammatory Cytokine. Western blot was used for measuring various proteins expressions. These results revealed that ß-elemene inhibited atherosclerotic lesion size and increased stability of plaques in ApoE-/- mice by alleviating levels of vascular oxidative stress and preventing pro-inflammatory cytokine production. In addition ß-elemene maintained endothelial function by significantly improving plasma nitrite and nitrate levels and expression of phosphorylation-eNOS in vivo. ß-elemene also increased the production of the nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) and promoted phosphorylation of eNOSser1177 and Akt in vitro. In Conclusive, data revealed that ß-elemene attenuated atherosclerosis and enhanced stability of plaques at least partially through its antioxidative and anti-inflammatory features and protected against endothelial dysfunction in ApoE-/- mice.

Multi-model-based interactive authoring environment for creating shareable medical knowledge.

OBJECTIVE: Technologically integrated healthcare environments can be realized if physicians are encouraged to use smart systems for the creation and sharing of knowledge used in clinical decision support systems (CDSS). While CDSSs are heading toward smart environments, they lack support for abstraction of technology-oriented knowledge from physicians. Therefore, abstraction in the form of a user-friendly and flexible authoring environment is required in order for physicians to create shareable and interoperable knowledge for CDSS workflows. Our proposed system provides a user-friendly authoring environment to create Arden Syntax MLM (Medical Logic Module) as shareable knowledge rules for intelligent decision-making by CDSS. METHODS AND MATERIALS: Existing systems are not physician friendly and lack interoperability and shareability of knowledge. In this paper, we proposed Intelligent-Knowledge Authoring Tool (I-KAT), a knowledge authoring environment that overcomes the above mentioned limitations. Shareability is achieved by creating a knowledge base from MLMs using Arden Syntax. Interoperability is enhanced using standard data models and terminologies. However, creation of shareable and interoperable knowledge using Arden Syntax without abstraction increases complexity, which ultimately makes it difficult for physicians to use the authoring environment. Therefore, physician friendliness is provided by abstraction at the application layer to reduce complexity. This abstraction is regulated by mappings created between legacy system concepts, which are modeled as domain clinical model (DCM) and decision support standards such as virtual medical record (vMR) and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT). We represent these mappings with a semantic reconciliation model (SRM). RESULTS: The objective of the study is the creation of shareable and interoperable knowledge using a user-friendly and flexible I-KAT. Therefore we evaluated our system using completeness and user satisfaction criteria, which we assessed through the system- and user-centric evaluation processes. For system-centric evaluation, we compared the implementation of clinical information modelling system requirements in our proposed system and in existing systems. The results suggested that 82.05% of the requirements were fully supported, 7.69% were partially supported, and 10.25% were not supported by our system. In the existing systems, 35.89% of requirements were fully supported, 28.20% were partially supported, and 35.89% were not supported. For user-centric evaluation, the assessment criterion was 'ease of use'. Our proposed system showed 15 times better results with respect to MLM creation time than the existing systems. Moreover, on average, the participants made only one error in MLM creation using our proposed system, but 13 errors per MLM using the existing systems. CONCLUSION: We provide a user-friendly authoring environment for creation of shareable and interoperable knowledge for CDSS to overcome knowledge acquisition complexity. The authoring environment uses state-of-the-art decision support-related clinical standards with increased ease of use.

Safety assessment and antioxidant activity of Lantana montevidensis leaves: Contribution to its phytochemical and pharmacological activity.

Lantana camara, the widely studied species, and L. montevidensis, the less studied species of the genus Lantana are both used in traditional medicine for the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is known about the toxicity of L. montevidensis and there is limited information on its chemical constituents. Here, we investigated for the first time the genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from the leaves of Lantana montevidensis in human leukocytes, as well as their possible interaction with human erythrocyte membranes in vitro. The antioxidant activities of both extracts were also investigated in chemical and biological models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 µg/mL) did not affect DNA damage index, but promoted cytotoxicity at higher concentrations (240-480 µg/mL). Both extracts did not modify the osmotic fragility of human erythrocytes. The extracts scavenged DPPH radical and prevented Fe2+-induced lipid peroxidation in rat's brain and liver homogenates, and this was likely not attributed to Fe (II) chelation. The HPLC analysis of the extracts showed different amounts of polyphenolic compounds (isoquercitrin, gallic acid, catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin, quercetin, chlorogenic acid, luteolin) that may have contributed to these effects. These results supported information on the functional use of L. montevidensis in folk medicine.

Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants.

Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc. The toxicity of reactive species is balanced by the integrated antioxidant systems, which include enzymatic and non-enzymatic antioxidants. Antioxidant therapies or defenses protect the biological sites by removing or quenching the free radicals (prooxidants). Medicinal plants can not only protect the oxidative damage, but also play a vital role in health maintenance and prevention of chronic degenerative diseases. This review will provide a valuable discussion of one hundred (100) well known medicinal plants, which may add to the optimization of antioxidants rank. Besides, some of the antioxidant evaluation techniques or mechanisms via which medicinal plants act as antioxidants are also described.

Allelopathic potential of oil seed crops in production of crops: a review.

Agricultural production enhancement has been realized by more consumption of fossil energy such as fertilizer and agrochemicals. However, the production provides the present human with sufficient and diversified commodities, but at the same time, deprives in some extent the resources from the future human as well. In the other hand, it is known that synthetic herbicides face worldwide threats to human's health and environment as well. Therefore, it is a great challenge for agricultural sustainable development. The current review has been focussed on various oilseed crop species which launch efficient allelopathic intervention, either with weeds or other crops. Crop allelopathic properties can make one species more persistent to a native species. Therefore, these crops are potentially harmful to both naturalized as well as agricultural settings. On the other side, allelopathic crops provide strong potential for the development of cultivars that are more highly weed suppressive in managed settings. It is possible to utilize companion plants that have no deleterious effect on neighbor crops and can be included in intercropping system, thus, a mean of contributing to agricultural sustainable development. In mixed culture, replacement method, wherein differing densities of a neighbor species are planted, has been used to study phytotoxic/competitive effects. So, to use alternative ways for weed suppression has become very crucial. Allelochemicals have the ability to create eco-friendly products for weed management, which is beneficial for agricultural sustainable development. Our present study assessed the potential of four oilseed crops for allelopathy on other crops and associated weeds.

Gas chromatography coupled with mass spectrometric characterization of Curcuma longa: Protection against pathogenic microbes and lipid peroxidation in rat's tissue homogenate.

The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.

Ethanolic extract of Nigella sativa protects Fe(II) induced lipid peroxidation in rat's brain, kidney and liver homogenates.

The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 µg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25-200µg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases.

Development of HPLC method by UV-VIS detection for the quantification of phenolic acids in different Ocimum sanctum Linn. extracts.

A simple and rapid chromatographic method has been developed for the simultaneous determination of five phenolic acids including Gallic acid, Chloroganic acid, Syringic acid, Benzoic acid and Vanillic acid by HPLC with UV-VIS detector. These Phenolic acids were separated by analytical column Intersil ODS-3 C18, a gradient elution system of ACN and acidified water solution with 1ml/min flow rate and quantified in a total run of 30 minutes at 210nm wavelength. In the quantitative analysis of these compounds showed good regression (0.995-0.999). The limit of detection [LOD] and limit of quantification [LOQ] of these compounds were in the range of 0.15-0.46 and 0.42-2.47 ßg/mL. The average recoveries were between 95.8-103.1% and their RSD values were less than 3.34%. By the proposed method Gallic acid, Chloroganic acid and Syringic acid were found and quantified in Methanolic, Ethanolic and Acetonic extract of Ocimum sanctum Linn. leaves. While the two other phenolic acids benzoic acid and vanillic acid was not found in the extracts of Ocimum sanctum Linn. leaves.

Lipid modulatory activities of Cichorium glandulosum Boiss et Huet are mediated by multiple components within hepatocytes.

To investigate a possible methodology of exploiting herbal medicine and design polytherapy for the treatment of non-alcoholic fatty liver disease (NAFLD), we have made use of Cichorium glandulosum Boiss et Huet (CG), a traditional Chinese herbal medicine that has been proven to be effective in treating hepatic diseases. Here, we report that the extract of CG effectively reduced lipid accumulation under conditions of lipid overloading in vivo and in vitro (in a rat high-fat diet model and a hepG2 cell model of free fatty acid treatment). CG extract also protected hepatocytes from injury and inflammation to aid its lipid-lowering properties (in a rat high-fat diet model and a L02 cell model of acetaminophen treatment). Serum chemistry analysis accompanied by in vitro drug screening confirmed that CG-4, CG-10 and CG-14 are the lipo-effective components of CG. Western blotting analysis revealed that these components can regulate key lipid targets at the molecular level, including CD36, FATP5 and PPAR-α, thus the lipid oxidation and lipid absorption pathways. Finally, we adopted the experimental design and statistical method to calculate the best combination proportion (CG-4: CG-10: CG-14 = 2.065: 1.782: 2.153) to optimize its therapeutic effect.

Hydrochlorothiazide and high-fat diets reduce plasma magnesium levels and increase hepatic oxidative stress in rats.

This study was designed to develop a rodent model of hydrochlorothiazide (HCTZ) toxicity by associating its intake with a high-fat (HF) diet. Rats were fed for 16 weeks with a control diet or with an HF diet supplemented or not with different doses of HCTZ. HCTZ, in a similar way to the HF diet, caused a significant increase in fructosamine levels. HCTZ and HF diet intake caused a significant reduction in magnesium and potassium levels, as well as an increase in lipid peroxidation and vitamin C in liver. Importantly, negative correlations were found between magnesium and glucose levels as well as between magnesium and fructosamine levels. The association between HCTZ and the HF diet caused additional worsening of biochemical parameters related to glucose homeostasis, and further increased hepatic oxidative stress. Our results suggest that chronic intake of HCTZ or an HF diet causes metabolic changes that are consistent with the development of insulin resistance. In addition, the association of an HF diet and HCTZ treatment can exacerbate some of these biochemical alterations, suggesting that this model might be useful for studying HCTZ metabolic toxicity.

Diphenyl diselenide supplementation reduces biochemical alterations associated with oxidative stress in rats fed with fructose and hydrochlorothiazide.

The study evaluated whether a diet containing diphenyl diselenide (PhSe)2, a synthetic antioxidant, could reduce the biochemical alterations induced by chronic consumption of highly enriched fructose diet and/or hydrochlorothiazide (HCTZ). Rats were fed a control diet (CT) or a high fructose diet (HFD), supplemented with or not HCTZ (4.0g/kg) and/or (PhSe)2 (3ppm) for 18weeks. HFD intake increased significantly plasma glucose, fructosamine, triglycerides and cholesterol levels. (PhSe)2 supplementation significantly reduced triglycerides and cholesterol but could not restore them to control levels. The combination of HFD and HCTZ significantly altered plasma glucose, fructosamine, triglycerides and cholesterol levels which were not restore by (PhSe)2 supplementation. Lipid peroxidation, protein carbonyl formation, vitamin C level and catalase activity decreased after HFD, HCTZ or HFD plus HCTZ ingestion. Remarkably (PhSe)2 supplementation restored the oxidative stress parameters. HCTZ decreased renal superoxide dismutase (SOD) activity, which was restored to control levels by (PhSe)2. Furthermore, the association of HFD and HCTZ decreased plasma potassium levels and aggravated HCTZ-induced hypomagnesemia and hypertriglyceridemia. Here we provided evidence of the involvement of oxidative stress and metabolic disorders in a rat model of HFD associated or not with HTCZ. (PhSe)2 supplementation reduced the oxidative stress and this compound should be considered for the treatment of biochemical disturbances and oxidative stress in other animal models of metabolic disorders.

pH-dependent Fe (II) pathophysiology and protective effect of an organoselenium compound.

Influence of pH on the extent of lipid peroxidation and the anti-oxidant potential of an organoselenium compound is explored. Acidosis increased the rate of lipid peroxidation both in the absence and presence of Fe (II) in rat's brain, kidney and liver homogenate and phospholipids extract from egg yolk. The organoselenium compound significantly protected lipids from peroxidation, both in the absence and presence of Fe (II). Changing the pH of the reaction medium did not alter the anti-oxidant activity of the tested compound. This study provides in vitro evidence for acidosis-induced oxidative stress in brain, kidney, liver homogenate and phospholipids extract and the anti-oxidant action of the tested organoselenium compound.