Design, Synthesis and Gene Modulation Insights into Pigments Derived from Tryptophan-Betaxanthin, Which Act against Tumor Development in Caenorhabditis elegans.

The use of betalains, which are nitrogenous plant pigments, by the food industry is widespread and reflects their safety after intake. The recent research showed outstanding results for L-tryptophan-betaxanthin, a phytochemical present in traditional Chinese medicine, as an antitumoral agent when the activity was evaluated in the animal model Caenorhabditis elegans. Thus, L-tryptophan-betaxanthin is now presented as a lead compound, from which eleven novel structurally related betaxanthins have been designed, biotechnologically produced, purified, and characterized. The antitumoral effect of the derived compounds was evaluated on the JK1466 tumoral strain of C. elegans. All the tested molecules significantly reduced the tumoral gonad sizes in a range between 31.4% and 43.0%. Among the novel compounds synthesized, tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin, which are the first betalains to contain an ester group in their structures, caused tumor size reductions of 43.0% and 42.6%, respectively, after administration to the model animal. Since these were the two most effective molecules, their mechanism of action was investigated by microarray analysis. Differential gene expression analysis showed that tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin were able to down-regulate the key genes of the mTOR pathway, such as daf-15 and rict-1.

Itaconate alleviates ß2-microglobulin-induced cognitive impairment by enhancing the hippocampal amino-ß-carboxymuconate-semialdehyde-decarboxylase/picolinic acid pathway.

ß2-microglobulin (B2M) has been established to impair cognitive function. However, no treatment is currently available for B2M-induced cognitive dysfunction. Itaconate is a tricarboxylic acid (TCA) cycle intermediate that exerts neuroprotective effects in several neurological diseases. The amino-ß-carboxymuconate-semialdehyde-decarboxylase (ACMSD)/picolinic acid (PIC) pathway is a crucial neuroprotective branch in the kynurenine pathway (KP). The present study sought to investigate whether Itaconate attenuates B2M-induced cognitive impairment and examine the mediatory role of the hippocampal ACMSD/PIC pathway. We demonstrated that 4-Octyl Itaconate (OI, an itaconate derivative) significantly alleviated B2M-induced cognitive dysfunction and hippocampal neurogenesis impairment. OI treatment also increased the expression of ACMSD, elevated the concentration of PIC, and decreased the level of 3-HAA in the hippocampus of B2M-exposed rats. Furthermore, inhibition of ACMSD by TES-991 significantly abolished the protections of Itaconate against B2M-induced cognitive impairment and neurogenesis deficits. Exogenous PIC supplementation in hippocampus also improved cognitive performance and hippocampal neurogenesis in B2M-exposed rats. These findings demonstrated that Itaconate alleviates B2M-induced cognitive impairment by upregulation of the hippocampal ACMSD/PIC pathway. This is the first study to document Itaconate as a promising therapeutic agent to ameliorate cognitive impairment. Moreover, the mechanistic insights into the ACMSD/PIC pathway improve our understanding of it as a potential therapeutic target for neurological diseases beyond B2M-associated neurocognitive disorders.

Interaction of picolinamide fungicide primary metabolites UK-2A and CAS-649 with the cytochrome bc1 complex Qi site: mutation effects and modelling in Saccharomyces cerevisiae.

BACKGROUND: Fenpicoxamid and florylpicoxamid are picolinamide fungicides targeting the Qi site of the cytochrome bc1 complex, via their primary metabolites UK-2A and CAS-649, respectively. We explore binding interactions and resistance mechanisms for picolinamides, antimycin A and ilicicolin H in yeast by testing effects of cytochrome b amino acid changes on fungicide sensitivity and interpreting results using molecular docking. RESULTS: Effects of amino acid changes on sensitivity to UK-2A and CAS-649 were similar, with highest resistance associated with exchanges involving G37 and substitutions N31K and L198F. These changes, as well as K228M, also affected antimycin A, while ilicicolin H was affected by changes at G37 and L198, as well as Q22E. N31 substitution patterns suggest that a lysine at position 31 introduces an electrostatic interaction with neighbouring D229, causing disruption of a key salt-bridge interaction with picolinamides. Changes involving G37 and L198 imply resistance primarily through steric interference. G37 changes also showed differences between CAS-649 and UK-2A or antimycin A with respect to branched versus unbranched amino acids. N31K and substitution of G37 by large amino acids reduced growth rate substantially while L198 substitutions showed little effect on growth. CONCLUSION: Binding of UK-2A and CAS-649 at the Qi site involves similar interactions such that general cross-resistance between fenpicoxamid and florylpicoxamid is anticipated in target pathogens. Some resistance mutations reduced growth rate and could carry a fitness penalty in pathogens. However, certain changes involving G37 and L198 carry little or no growth penalty and may pose the greatest risk for resistance development in the field. © 2022 Society of Chemical Industry.

Effect of Phosphate Binders and a Dietary Iron Supplement on the Pharmacokinetics of a Single Dose of Vadadustat in Healthy Adults.

Vadadustat is a hypoxia-inducible factor prolyl-hydroxylase inhibitor being developed for the treatment of anemia in patients with chronic kidney disease. Sequelae of chronic kidney disease include hyperphosphatemia and anemia, which are frequently treated with phosphate binders and iron supplements, respectively. Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. In study 1, 54 healthy women and men were administered vadadustat (300 mg) alone and 1 hour before, concurrently with, or 2 hours after a phosphate binder (sevelamer carbonate 1600 mg, calcium acetate 1334 mg, or ferric citrate 2000 mg). In study 2, 10 healthy men were administered vadadustat (450 mg) alone and concomitantly with the oral iron supplement ferrous sulfate (325 mg [equivalent to 65 mg of elemental iron]). Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, or ferrous sulfate. Geometric least squares mean ratios for area under the concentration-time curve from time 0 to infinity were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no-effect boundaries of +50% to -33%, indicating that drug-drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders. Vadadustat was well tolerated when administered in conjunction with phosphate binders or an iron supplement.

Residue Behavior of Clopyralid Herbicide in Soil and Sugar Beet Crop under Subtropical Field Conditions.

ABSTRACT: Sugar beet is a major crop for the sugar industry. With growing awareness of unsystematic use of pesticides, health problem, and environmental issues, assessment of pesticide residues in soil and crops has become necessary. Studies of subtropical conditions on dissipation and residue analysis of clopyralid have not yet been reported. Therefore, dissipation kinetics and terminal residues of clopyralid for two cropping seasons in the soil and the sugar beet crop were studied under field conditions. An experiment was laid out in a randomized block design, and a herbicide was applied as a postemergent. Clopyralid was extracted from the matrix by basic water, subjected to solid phase extraction cleanup, and quantified by high-pressure liquid chromatography-UV. The method was validated, and recovery percentage of pesticide ranged from 81 to 88, 77 to 85, 78 to 86, and 89 to 94% in the soil, sugar beet roots, sugar beet leaves, and water, respectively. After application in the soil, clopyralid dissipated rapidly following monophasic first-order kinetics, with a half-life of 13.39 days. Limits of detection and quantitation were 0.007 and 0.02 µg g-1, respectively. Clopyralid does not persist long in soil, and residues were below the European Union's maximum residue levels (0.5 mg kg-1) in the roots and leaves of sugar beet. Residues were also not detected in the groundwater. It can be concluded that clopyralid could be considered a safe herbicide from the environmental aspect due to its nonpersistence and that it would not have an adverse effect on human or animal health.

Determination of chromium(III) picolinate in dietary supplements by flow injection - electrospray ionization - tandem mass spectrometry, using cobalt(II) picolinate as internal standard.

In this work, a principle of flow injection analysis (FIA) was applied for sample introduction to an electrospray ionization - ion trap mass spectrometer (ESI-ITMS) with the aim to quantify chromium(III) picolinate (CrPic3) in commercial supplements by multiple reaction monitoring, and using cobalt(II) picolinate as internal standard (IS). FIA system was operated with ammonium formate 10 mmol L-1 in methanol-water (1:1, v/v) as a carrier solution at a flow rate 200 µL min-1; 100 µL injections were performed in 2-min intervals. Setting ion transitions m/z 419 â†’ 270 and 304 â†’ 260 for the analyte and IS, respectively, and 100 ms integration time, the method detection and quantification limits 12 ng g-1 and 40 ng g-1 of Cr (as CrPic3) in the air-dried powder. Acetonitrile extracts of the real-world samples presented varying from sample-to-sample chemical composition and IS efficiently compensated for ionization interferences. Mean results from triplicate analysis of four different supplements were obtained with relative standard deviation 0.1-4.0%, indicating acceptable precision. Trueness of the proposed FIA-ESI-ITMS/MS procedure was demonstrated by 95.8-108% percentage recoveries attained in the analysis of the CrPic3-spiked samples. For comparative purposes, total Cr was determined by ICP-MS. The quantitative results obtained indicate the necessity of analytical control of Cr(III) supplements commercially available and demonstrate that the proposed FIA-ESI-ITMS/MS procedure is well-suited for the determination of CrPic3 in such products.

Effects of Supplemental Chromium Nanoparticles on IFN-γ expression of Heat Stress Broilers.

The aim of present study was to investigate the beneficial effect of chromium (III) picolinate (CrPic) and chromium (III) picolinate nanoparticles (NCrPic) addition on growth performance, stress-related hormonal changes, and serum levels of various immunity biomarkers, as well as the gene expression of IFN-γ in broilers exposed to heat stress conditions. Treatments included T1 which received the basal diet with no feed additive; T2 exposed to heat stress; T3, T4, and T5 containing 500, 1000, and 1500 ppb CrPic; as well as T6, T7, and T8 containing 500, 1000, and 1500 ppb NCrPic, respectively. After 2 weeks from CrPic and NCrPic supplementation, IFN-γ mRNA expression was assayed using the RT-PCR technique. The results showed that the lower body weight, daily weight gain, daily feed intake by heat stress, and the feed conversion ratio were recovered remarkably by CrPic and NCrPic supplements. The stress-elevated levels of cortisol and immunoglobulin were reduced significantly using CrPic and NCrPic supplementation (P ≤ 0.05). The gene expression profile showed that the upregulated expression of IFN-γ was regulated by the addition of CrPic and NCrPic, in particular, to the diet; however, a full downregulation of IFN-γ expression was observed after week 2 of NCrPic supplementation. In conclusion, the results indicated that nanoparticle supplementation could be effective in reducing heat stress-induced detrimental alterations, thereby attributing to substantial changes to the immune system, including IFN-γ expression.

Tuning the lipophilic nature of pyclen-based 90Y3+ radiopharmaceuticals for ß-radiotherapy.

Pyclen-dipicolinate chelates proved to be very efficient chelators for the radiolabeling with ß--emitters such as 90Y. In this study, a pyclen-dipicolinate ligand functionalized with additional C12 alkyl chains was synthesized. The radiolabeling with 90Y proved that the addition of saturated carbon chains does not affect the efficiency of the radiolabeling, whereas a notable increase in lipophilicity of the resulting 90Y radiocomplex was observed. As a result, the compound could be extracted in Lipiodol® and encapsulated in biodegrable pegylated poly(malic acid) nanoparticles demonstrating the potential of lipophilic pyclen-dipicolinate derivatives as platforms for the design of radiopharmaceuticals for the treatment of liver or brain cancers by internal radiotherapy.

Magnesium Picolinate Improves Bone Formation by Regulation of RANK/RANKL/OPG and BMP-2/Runx2 Signaling Pathways in High-Fat Fed Rats.

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

Relationship between Antioxidant Activity and Ligand Basicity in the Dipicolinate Series of Oxovanadium(IV) and Dioxovanadium(V) Complexes.

Oxidative stress plays an important role in the pathogenesis of many serious diseases, including cancer, atherosclerosis, coronary artery disease, Parkinson's disease, Alzheimer's disease, stroke and myocardial infarction. In the body's natural biochemical processes, harmful free radicals are formed, which can be removed with the help of appropriate enzymes, a balanced diet or the supply of synthetic antioxidant substances such as flavonoids, vitamins or anthocyanins to the body. Due to the growing demand for antioxidant substances, new complex compounds of transition metal ions with potential antioxidant activity are constantly being sought. In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2'-bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) [VO(dipic)(H2O)2]·2 H2O, (2) [VO(dipic)(phen)]·3 H2O, (3) [VO(dipic)(bipy)]·H2O and (4) [VOO(dipic)](2-phepyH)·H2O were synthesized including one new complex, so far unknown and not described in the literature, i.e., [VOO(dipic)](2-phepyH)·H2O. The oxovanadium(IV) dipicolinate complexes with 1,10-phenanthroline and 2,2'-bipyridyl have been characterized by several physicochemical methods: NMR, MALDI-TOF-MS, IR, but new complex [VOO(dipic)](2-phepyH)·H2O has been examined by XRD to confirm its structure. The antioxidant activities of four complexes have been examined by the nitrotetrazolium blue (NBT) method towards superoxide anion. All complexes exhibit high reactivity with superoxide anion and [VOO(dipic)](2-phepyH)·H2O has higher antioxidant activity than L-ascorbic acid. Our studies confirmed that high basicity of the auxiliary ligand increases the reactivity of the complex with the superoxide radical.

In Vitro and Clinical Pharmacokinetic Studies of the Effects of Iron-containing Agents on Vadadustat, an Oral Hypoxia-inducible Factor-Prolyl Hydroxylase Inhibitor.

PURPOSE: Vadadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in chronic kidney disease. This study investigated drug-drug interactions between vadadustat and oral iron supplements or iron-containing phosphate binders commonly used in Japanese clinical practice by conducting in vitro mechanistic and clinical pharmacokinetic studies. METHODS: In the in vitro assessment, chelate formation of vadadustat with iron-containing agents was investigated in water and in a fed-state simulated intestinal fluid. Chelate formation was assessed by observation of a chelate-specific color, and the concentration of vadadustat was determined. In the single-dose, open-label, randomized, crossover clinical study, healthy male participants received 150 mg of vadadustat with or without oral iron-containing agents. Pharmacokinetic data were collected for up to 24 hours after vadadustat administration. Participants were monitored for adverse events during the study. FINDINGS: Vadadustat formed a chelate precipitate with ferrous sulfate and ferric nitrate, as shown by development of a specific bright orange color in water. The proportions of vadadustat dissolved in the supernatant were 2% and 18%, respectively. Vadadustat did not form a chelate precipitate in a fed-state simulated intestinal fluid in the presence of sodium ferrous citrate, ferric citrate hydrate, or sucroferric oxyhydroxide; the proportion of vadadustat in supernatant ranged from 63% to 89%. In the clinical pharmacokinetic study, coadministration of vadadustat with sodium ferrous citrate, ferric citrate hydrate, sucroferric oxyhydroxide, or ferrous sulfate decreased the AUC0-∞ by 54.0% to 89.7% and Cmax by 42.1% to 91.9%. No serious adverse events were reported. IMPLICATIONS: Chelate formation of vadadustat with iron-containing agents was confirmed by in vitro analysis and depended on the type of iron-containing agent. The AUC0-∞ and Cmax of vadadustat decreased when coadministered with oral iron-containing agents. Our data suggest that the decreases in AUC0-∞ and Cmax are a result of chelation in the gastrointestinal tract; therefore, coadministration of iron-containing agents with vadadustat should use a dosing interval. ClinicalTrials.gov Identifier: NCT03645863.

Magnetism-mediated targeting hyperthermia-immunotherapy in "cold" tumor with CSF1R inhibitor.

Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called "cold" tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in "cold" colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an "eat-me" signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8+ T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.

Comparative evaluation of different methods for determining phytochemicals and antioxidant activity in products containing betalains - Verification of beetroot samples.

This study presents methods that can be used to assess the health quality of products containing betalains. The paper compares and verifies data on the phytochemical composition of three different pigmented beetroot cultivars using spectrophotometric, HPLC-DAD, HPTLC and LC-Q-Orbitrap-HRMS techniques. Additionally, we compared the total antioxidant activity in both the cell-free and cellular systems. Betalain contribution to antioxidant activity was also determined using post-column derivatization and it was found that in the case of red beetroot it is about 50%. Photometric measurements are recommended for a simple and inexpensive analysis of the total betacyanin and betaxanthin content. Liquid chromatography techniques produced more precise information on phytochemical composition in the tested samples. The combination of liquid chromatography with high-resolution mass spectrometry produced the largest amount of quantitative and qualitative data; in beetroot samples sixty-four phytochemicals have been identified therefore, this approach is recommended for more detailed metabolomics studies.

Effects of dietary chromium picolinate supplementation on broiler growth performance: A meta-analysis.

OBJECTIVE: A meta-analysis was conducted to assess the effects of dietary chromium picolinate (CrPic) supplementation on broiler growth performance and to determine whether such effects are regulated by broiler strains, sex, environmental stress, or contextual factors including study area and years. METHODS: Eligible studies were identified by searching the Web of Science, Springer, Elsevier, ScienceDirect, Taylor & Francis Online databases. Weighted average differences with corresponding 95% confidence intervals were computed with a random-effects model. We performed subgroup analysis stratified by study area, published years, broiler strains and sex, and environmental stress. Publication bias was assessed with Egger's test method. A total of 15 studies eligible for inclusion. RESULTS: The results indicated that CrPic supplementation significantly improved broiler growth performance and subgroup analysis confirmed this conclusion. We also found that Ross 308 or male broilers might be more sensitive to CrPic supplementation and showed better growth performance. A model was used to obtain the amount of chromium addition under the optimal growth performance, which suggested that the maximum value of average daily gain (ADG) was reached when chromium addition was 1810 µg/kg. The results of the sensitivity analysis showed low sensitivity and high stability of the meta-analysis. CONCLUSIONS: CrPic supplementation had a positive effect on the growth performance of broilers, and this meta-analysis provides a more accurate value of chromium addition, which may be beneficial for the practice of the broiler industry.

Cytotoxic and genotoxic effects of clopyralid herbicide on Allium cepa roots.

Clopyralid is one of the synthetic pyridine-carboxylate auxin herbicides and used to control perennial and annual broadleaf weeds in wheat, sugar beets, canola, etc. In this study, dose-dependent cytotoxicity and genotoxicity of clopyralid at different concentrations (25, 50, and 100 µg/mL) have been evaluated on the Allium cepa roots. The evaluation has been performed at macroscopic (root growth) and microscopic levels [mitotic index (MI), chromosome aberrations (CAs) in ana-telophase cells, and DNA damage] using root growth inhibition, Allium ana-telophase, and comet tests. The percentage of root growth inhibition and concentration of reducing root growth by 50% (EC50) of clopyralid were determined compared with the negative control by using various concentrations of clopyralid (6.25-1000 µg/L). The 96 h EC50 of clopyralid was recorded as 50 µg/L. The gradual decrease in root growth and the MI reveals the cytotoxic effects of clopyralid. All the tested concentrations of clopyralid induced total CAs (polyploidy, stickiness, anaphase bridges, chromosome laggards, and disturbed ana-telophase) and DNA damage dose and time dependently. These results confirm the cytotoxic and genotoxic effects of clopyralid on non-target organism.

Improvement in the growth status and carbohydrate utilization of Labeo rohita (Hamilton, 1822) fingerlings with dietary supplementation of chromium picolinate.

A 60-day feeding experiment was conducted to evaluate the effects of dietary chromium (Cr) on carbohydrate utilization and growth performance of Labeo rohita fingerlings. Fishes were fed with four high carbohydrate (53%), isonitrogenous (crude protein 35%), and isocaloric (415 Kcal, 100 gm-1) experimental diets containing different levels of dietary chromium picolinate (Cr-Pic) viz.0, 400, 800, and 1200 µg kg-1 diet. Weight gain (WG%), specific growth rate (SGR), feed efficiency ratio (FER), and protein efficiency ratio (PER) were significantly increased at 800 µg kg-1 diet chromium supplementation (P < 0.05). Cr-Pic supplementation (800 µg kg-1) also significantly (P < 0.05) enhanced the protein: DNA ratio in muscle, while DNA: RNA and DNA: tissue ratios were significantly (P < 0.05) decreased indicating higher growth. Significantly higher amylase, protease, and lipase activities were recorded in 800 µg Cr-Pic kg-1 diet fed fishes (P < 0.05), while any of the experimental groups showing no significant (P > 0.05) change in hexokinase activity, indicating normal glycolysis in all. Furthermore, significant (P < 0.05) decrease of glucose-6-phospatase activity in 800 µg Cr-Pic kg-1 diet fed group, showcasing an evidence for protein-sparing action with Cr-Pic supplementation. Significantly (P < 0.05) higher serum insulin and liver glycogen in 800 µg Cr-Pic kg-1 diet fed fishes denote an improvement in carbohydrate metabolism. However, significantly (P < 0.05) higher ATPase and SOD activities were also observed when chromium supplementation was more than 800 µg kg-1 diet, indicating stress at higher level. The present study indicates that growth and carbohydrate utilization can significantly (P < 0.05) be improved by feeding the L. rohita fingerlings with Cr-Pic (800 µg kg-1 diet) supplemented diet in laboratory condition.

Study Protocol for a Randomized Controlled Trial Evaluating the Effectof Chromium Picolinate Supplementation on Gene Expression of TumorNecrosis Factor-α and DNA Damage in Metabolic Syndrome Patients.

Metabolic syndrome (MS) is caused by environmental factors as well as genetic. Human studies of efficacy of chromium for glucose and lipid metabolism and insulin function is not still definitive. Furthermore, the effect of chromium supplementation on the expression of inflammatory genes in patients with MS has not been studied. We will assess effects of chromium picolinate supplementation on gene expression of tumor necrosis factor-α (TNF-α) and DNA damage in MS patients. In this triple-blind randomized placebo-controlled clinical trial, 48 MS patients will be randomly assigned into two groups to receive daily 400 µg chromium picolinate supplement or placebo for 12 weeks. The outcome measures include of change in fasting blood sugar, glycosylated hemoglobin A1C, inflammatory biomarkers, lipid profile, blood pressure, gene expression of TNF-α, and 8-hydroxy-deoxyguanosine concentration as DNA damage biomarker, will be quantified at baseline and end of intervention. This protocol was approved by Institutional Research Ethics Committee School of Public Health Shahid Sadoughi University of Medical Sciences (Approval ID: IR.SSU.SPH.REC.1399.141).

Chromium picolinate balances the metabolic and clinical markers in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a complicated disease and is considered as a severe global health problem affecting 30% of adults worldwide. The present study aimed to evaluate changes in oxidative stress, adipokines, liver enzyme, and body composition following treatment with chromium picolinate (CrPic) among patients with NAFLD. PARTICIPANTS AND METHODS: The current randomized, double-blind, placebo-controlled study was conducted on 46 NAFLD patients with the age range of 20-65 years. Patients were randomly classified into two groups, receiving either 400 µg CrPic tablets in two divided doses of 200 µg (23 patients) or placebo (23 patients) daily for 12 weeks. The participants' body composition and biochemical parameters were evaluated at the baseline and after 12 weeks. RESULTS: Serum levels of liver enzymes reduced significantly only in the CrPic group (P < 0.05 for all), but not between the groups after the intervention. Besides, there were significant differences between the study groups regarding body weight and body fat mass, total antioxidant capacity, superoxide dismutase, malondialdehyde, leptin, and adiponectin post-intervention (P = 0.017, P = 0.032, P = 0.003, P = 0.023, P = 0.012, P = 0.003, and P = 0.042, respectively). However, glutathione peroxidase and resistin levels did not differ significantly between groups (P = 0.127 and P = 0.688, respectively). DISCUSSION AND CONCLUSION: This study showed that consuming 400 µg/day of CrPic for 12 weeks in patients with NAFLD causes a significant change in leptin, adiponectin, oxidative stress (expect glutathione peroxidase), and body weight, compared to baseline. Nevertheless, it does not affect liver enzymes. Therefore, the CrPic supplementation may improve adipokines, some anthropometric indices, and oxidative stress in patients with NAFLD.

A pilot study of the effects of chromium picolinate supplementation on serum fetuin-A, metabolic and inflammatory factors in patients with nonalcoholic fatty liver disease: A double-blind, placebo-controlled trial.

BACKGROUND: Evaluating the impact of chromium picolinate supplementation on glycemic status, lipid profile, inflammatory markers and fetuin-A in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In present research, participants (N = 46) were randomized to (400 mcg/day, n = 23) chromium picolinate and placebo (n = 23) for 3 months. RESULTS: Glucose indices, and lipid profiles, inflammatory biomarker and fetuin-A were measured before and after the intervention. Chromium reduced triglyceride (TG), atherogenic index of plasma (AIP), very-low-density lipoprotein (VLDL), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL) -6, tumor necrosis factor-alpha (TNF-α) and fetuin-A significantly compared to placebo group (p < 0.05). Furthermore, chromium significantly increased the quantitative insulin sensitivity check index (QUICKI). There were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), fasting blood sugar (FBS), Hemoglobin A1c (HbA1C), interleukin (IL)-17 between the two groups (p < 0.05). CONCLUSION: Chromium picolinate significantly decreased TG, insulin, HOMA-IR, fetuin-A, the number of inflammatory factors, and increased QUICKI without changing FBS, HbA1C, TC, LDL, HDL, IL-17 levels and liver steatosis intensity in patients with NAFLD. Further studies by examining the effect of different doses of chromium and mechanisms of cellular action, would help further clarify the subject.

The effect of the high-fat diet supplemented with various forms of chromium on rats body composition, liver metabolism and organ histology Cr in liver metabolism and histology of selected organs.

BACKGROUND: In the present study, we hypothesized that feeding rats a high-fat diet negatively affects liver metabolism and function and disturbs the histology of some internal organs. We also postulated that there is a form of chromium whose administration alleviates the negative effects of a high-fat diet in rats. METHODS: To verify the hypotheses, we tested the effect of various forms of chrome (picolinate - Cr-Pic, Chromium(III)-methionine complex - Cr-Met, and chrome nanoparticles - Cr-NPs) applied in the recommended amount of 0.3 mg/kg of BW on growth parameters, body fat, liver metabolism and functional disorders, and histological parameters of selected internal organs in rats fed a standard (S) or high-fat diet (F). The experiment was conducted on 56 male outbred Wistar rats (Rattus norvegicus. Cmdb:WI) randomly divided into eight experimental groups. For eight weeks the rats received a standard or high-fat diet, without Cr or with Cr at 0.3 mg/kg diet in the form of Cr-Pic, Cr-Met or Cr-NPs. RESULTS AND CONCLUSION: The use of a F diet disrupted the lipid-carbohydrate profile, worsened liver metabolism and function, reduced the expression of hepatic PPAR-α and leaded to negative changes in the histological image of internal organs - liver, kidneys and pancreas. The 8-week use of an chromium supplement in a F diet, regardless of the form used, did not improve the ratio of fat tissue to lean tissue, worsened liver function and negatively affected on the histological image of the liver, kidneys and pancreas. However, the most negative changes in lipid-carbohydrate metabolism and liver functioning were observed with CrNPs supplementation.