Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.

Antidyslipidemic, Antioxidant, and Anti-inflammatory Effects of Jelly Drink Containing Polyphenol-Rich Roselle Calyces Extract and Passion Fruit Juice with Pulp in Adults with Dyslipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress and inflammation play key roles in the pathophysiology in the pathophysiology of dyslipidemia, which are positive risks that increase atherosclerosis leading to important healthcare problems. Therefore, we aimed to study the antioxidant, anti-inflammatory, and lipid-lowering effects of jelly drink containing polyphenol-rich roselle calyces extract and passion fruit juice with pulp concentrate (RP jelly drink) in comparison to a placebo jelly drink for 8 weeks. Forty-three adults with dyslipidemia were randomly assigned into two groups: the RP jelly drink group and the placebo group. Glucose, total cholesterol (TC) triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), oxidative stress biomarkers, inflammatory parameters, and monocyte chemotactic protein-1 (MCP-1) were measured with fasting blood samples at baseline, 4 weeks and 8 weeks of intervention. Results showed a significant decrease in LDL-C and TG, respectively, after 8 weeks of RP jelly drink consumption (LDL-C: 107.63 ± 22.98 mg/dL; TG: 109.79 ± 38.83 mg/dL) compared to baseline measurements (LDL-C: 128.43 ± 32.74 mg/dL; TG: 132.33 ± 75.11 mg/dL). These may be possible due to reduced inflammation and improvements in oxidative stress, as demonstrated by the reduction of tumor necrosis factor- (TNF-) α and malondialdehyde (MDA), and the enhancement of glutathione (GSH) after consuming the RP jelly drink for 8 weeks. However, no significant differences of treatment on glucose, total cholesterol, MCP-1, interleukin-6, and interleukin-10 were observed. In conclusion, daily consumption of RP jelly drink for 8 weeks resulted in significant improvement in lipid profiles in subjects with dyslipidemia. However, more research is needed to assess its nutritional and functional potential.

Phyllanthus emblica L. Regulates BDNF/PI3K Pathway to Modulate Glutathione for Mitoprotection and Neuroprotection in a Rodent Model of Ischemic Stroke.

INTRODUCTION: Ischemic stroke remains the leading cause of death worldwide and is the primary cause of disability globally. Numerous studies have shown that plant-origin medicines are promising and can influence the treatment of neurological disorders. Phyllanthus embilica L. (P. emblica or Amla) is one of the herbal plants whose medicinal properties are widely studied. The objective of the present study is to determine the neuroprotective effects of an aqueous extract of the fruit of P. emblica (hereinafter referred to as just P. emblica) on cerebral ischemia-reperfusion injury and explore if it can regulate BDNF/PI3K pathway to modulate glutathione for mitoprotection and neuroprotection. METHODS: In vivo studies were conducted on male Sprague Dawley rats, where rats were prophylactically administered 100 mg/kg P. emblica for 30 days. In the treatment group, rats were given 100 mg/kg P. emblica, 1 h post middle cerebral artery occlusion (MCAo). Rats were evaluated for neuro deficit and motor function tests. Brains were further harvested for infarct size evaluation, biochemical analysis, protein expression studies, and mitochondrial studies. RESULTS: Prophylaxis and treatment with P. emblica demonstrated significant improvement in functional outcome with a reduction in infarct size. Normalization of glutathione, nitrite, and malondialdehyde levels was also observed. Improvement in mitochondrial complex I and IV activities was also reported. Expressions of BDNF, PI3K, SDF1 and VEGF increased while that of ROCK2 decreased following P. emblica administration. CONCLUSION: P. emblica regulates BDNF/PI3K pathway to modulate glutathione in ischemic stroke to confer mitoprotection and neuroprotection.

Ultrathin-FeOOH-Coated MnO2 Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy.

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin-FeOOH-coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)-triggered ROS but also tune the TME by hypoxia alleviation, H2 O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1 O2 ) and hydroxyl radicals (• OH) by inhibiting the recombination of US-initiated electron-hole pairs and Fenton-like reaction, respectively. Additionally, the catalase-like and GSH peroxidase-like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA-MB-231-tumor-bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy.

Omega 3 fatty acids can reduce early doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukemia.

OBJECTIVES: Omega 3 polyunsaturated fatty acids are dietary factors with several beneficial cardiovascular effects. This study aimed to assess the possible protective effect of omega 3 fatty acids on early doxorubicin-induced cardiac toxicity in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty children of newly diagnosed ALL were randomized into two groups: group I (n = 30) who received omega 3 fatty acids 1000 mg/day for 6 months in addition to their usual protocol of chemotherapy including doxorubicin; and group II (n = 30) who received their usual doxorubicin protocol during the period from February 2020 till August 2021. Echocardiographic examinations were performed before and after the treatment. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), troponin I, creatine kinase MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured also before and after omega 3 treatment. RESULTS: After 6 months of omega 3 administration, group I had a significantly lower MDA level and a significantly higher glutathione and SOD levels than group II. Similarly, the levels of troponin I, CK-MB, and NT-proBNP were significantly high in group II, whereas they were unchanged in group I after treatment. Similarly, systolic function (presented with peak mitral annular systolic velocity and two-dimensional global longitudinal strain) of the heart was preserved in omega 3-treated patients, unlike the control group that showed significant impairment of left ventricular function after 6 months. CONCLUSION: Omega 3 fatty acids may decrease early cardiac injury and doxorubicin-induced cardiotoxicity in children with ALL.

The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial.

BACKGROUND: Glutathione has become a potential skin-lightening ingredient after the discovery of its anti-melanogenic properties. Various mechanisms of action have been considered to explain this property, one of them being the skewing of the melanin synthesis pathway toward the production of lighter pheomelanin instead of darker eumelanin, consequently producing a lightening effect. AIMS: To evaluate the skin lightening and anti-dark spot effects of oral supplementation with L-Cystine associated with L-Glutathione as compared to placebo and benchmark. METHODS: Effects of this L-Cystine-L-Glutathione oral combination were investigated in a 12-week randomized, double-blind, parallel-group, benchmark- and placebo-controlled trial involving 124 Asian female subjects. Women were randomly allocated into 4 equal groups (500 mg L-Cystine and 250 mg L-Glutathione, 250 mg reduced L-Glutathione, 500 mg L-Cystine, or a placebo, daily). Skin color was measured at baseline, after 6 and 12 weeks by spectrophotometry. Size and color of facial dark spots were determined from digital photographs. RESULTS: A significant skin lightening was observed after 12 weeks of oral supplementation with L-Cystine associated with L-Glutathione. This combination also induced a significant reduction in the size of facial dark spots after 6 and 12 weeks. It is noteworthy that the observed effects were not only significantly better than those obtained with placebo, but also with L-Cystine alone or L-Glutathione alone. CONCLUSION: The daily oral administration of 500 mg L-Cystine and 250 mg L-Glutathione during 12 weeks was a safe treatment to effectively lighten the skin and reduce the size of facial dark spots of Asian women.

Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.

Lipid peroxidation aggravates anti-tuberculosis drug-induced liver injury: Evidence of ferroptosis induction.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

NMR-based metabolomics approach reveals effects of antioxidant nutrients in sepsis-induced changes in rat liver injury.

Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of sepsis. In excess, oxidative stress is not deemed an unbalanced biochemical reaction in the critically ill rats, but it is a key pathological factor in driving systemic inflammatory response that can result in multiple organ failure in sepsis. Thus, we aimed to explore whether antioxidant nutrients could reduce or delay the oxidative stress condition of sepsis rats, and then play a prospective role in the oxidative stress condition of critical disease. In this investigation, the ability of exogenous and endogenous antioxidant nutrients (ascorbate, taurine and glutathione) to prevent sepsis-induced changes in liver injury was examined using a rat model of sepsis induced by cecal ligation and puncture (CLP), and the underlying mechanisms were also investigated. The effects of three antioxidants on sepsis were assessed based on biochemical assays in combination with an NMR-based metabolomics approach and correlation network analysis. Our results suggested that ascorbate, taurine and glutathione had broadly similar protective effects on reducing oxidative stress. Compared with CLP rats, antioxidant-treated rats exhibited alleviated (P<.05) organ dysfunction and improved liver pathology. Moreover, taurine showed a better efficacy compared with ascorbate and glutathione, evidenced by significantly reversed metabolomics profiles toward normal state. Under conditions of sepsis, antioxidants suppressed inflammatory responses by restraining key signaling pathways, including the redox-sensitive transcription factor pathways of NF-κB and MAPK. Collectively, our findings suggested that antioxidant nutrients exerted beneficial effects on septic rats via protecting mitochondrial.

The Development of a Nano-based Approach to Alleviate Cisplatin-Induced Ototoxicity.

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles' ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

The Use of Intravenous Glutathione for Symptom Management of Parkinson's Disease: A Case Report.

Intravenous glutathione has been suggested empirically to improve Parkinson's disease (PD) symptoms of tremor and rigidity, but there is limited supporting research. This case report demonstrates both subjective and objective symptom improvement of a conventionally-treated patient suffering from PD when adjunctive intravenous glutathione was administered. In addition to suggesting clinical benefit, this case also suggests an effective therapeutic frequency of therapy and a minimal therapeutic dose. The consistent pattern of improvement following glutathione injections asserts that this therapy may improve symptoms common to PD patients and can offer additional quality of life that would be otherwise unattainable to these patients.

Protective effects of glutathione on oxidative injury induced by hydrogen peroxide in intestinal epithelial cells.

BACKGROUND: Reactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species-mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)-induced injury in intestinal epithelial cells. METHODS: IEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion. Terminal deoxynucleotidyl transferase-mediated UTP end-labeling staining and cleaved caspase-3 were used to assess apoptosis. The role of P38 mitogen-activated protein kinase (P38 MAPK) signaling was examined using the P38 MAPK agonist U46619 and inhibitor SB203580 in H2O2 and GSH-treated cells. Phosphorylated and total P38 MAPKs and cleaved caspase-3 were measured by Western blot. Data are means ± standard deviation, statistical significance P < 0.05 by student's t-test, or one-way analysis of variance. RESULTS: Pretreatment with GSH attenuates the activation of NF-κB and P38 MAPK signaling pathways by H2O2. GSH also decreased H2O2-mediated increases in interleukin 1 beta secretion, cleaved caspase-3 activation, and apoptosis in IEC-6 cells. SB203580 attenuated the increase in apoptosis and cleaved caspase-3 in H2O2-treated cells. The increase in apoptotic index and cleaved caspase-3 observed in U46619-treated cells was also diminished by GSH. CONCLUSIONS: GSH appears to ameliorate oxidative injury in intestinal epithelial cells by attenuating H2O2-mediated activation of NF-κB and P38 MAPK signaling pathways that regulate intestinal inflammation and apoptosis.

Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.

OBJECTIVE: Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF). METHODS: We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000. RESULTS: In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (≤1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively). CONCLUSIONS: Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.

Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.

BACKGROUND: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson's disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD. OBJECTIVE: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study. METHODS: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH thrice daily for three months, and were observed over a one-month washout period. RESULTS: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (-4.6 (4.7), P = 0.0025) and UPDRS motor subscore (-2.2 (3.8), P = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy. CONCLUSIONS: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation.

Comparison of the effect of a combination of eight micronutrients versus a standard mono preparation on sperm parameters.

BACKGROUND: There are reports showing that l-carnitine alone or in combination with other micronutrients improve sperm parameters. However, comparative studies are still lacking. This study was carried out to compare the short term effects of a combination of eight micronutrients including l-carnitine vs. a mono-substance (l-carnitine alone) on sperm parameters. METHODS: This was a prospective, open-labelled, nonrandomized study that included male subjects (20 to 60 years) with at least 1 year of subfertility and at least one pathological semen analysis who received 3 months treatment with a mono-substance (500 mg l-carnitine/twice a day, n = 156) or a combined compound (440 mg l-carnitine + 250 mg l-arginine + 40 mg zinc + 120 mg vitamin E + 80 mg glutathione + 60 µg selenium + 15 mg coenzyme Q10 + 800 µg folic acid/once a day, n = 143) for the same time period. Sperm parameters were analyzed before and after treatment and groups comparisons performed. RESULTS: Baseline characteristics were similar among studied groups (age and body mass indices). Semen parameters (volume, density, overall progressive motility [including slow and fast motility]) and percentage of sperm with normal morphology improved after 3 months in both groups as compared to baseline. However, relative change (expressed as % increase of absolute values) for sperm density and overall progressive motility (including fast motility) was found to be higher for the combined micronutrient treatment group as compared to the mono-treatment using l-carnitine alone. CONCLUSION: Both analyzed groups displayed a positive short term effect on all sperm parameters; however effect on density and motility was significantly better for the combined formulation. There is need for more research in this matter that includes long term outcome data. TRIAL REGISTRATION: Retrospectively registered at ISRCTN (7th October 2016). Study ID: ISRCTN48594239.

Male infertility: lifestyle factors and holistic, complementary, and alternative therapies.

While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT) include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.

Oral glutathione supplementation drastically reduces Helicobacter-induced gastric pathologies.

Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known on the metabolism of this bacterium and its impact on the host. In this study, we have revealed the importance of the glutamate-generating metabolism, as shown by a complete depletion of glutamine (Gln) in the medium during H. suis culture. Besides Gln, H. suis can also convert glutathione (GSH) to glutamate, and both reactions are catalyzed by the H. suis γ-glutamyltranspeptidase (GGT). Both for H. pylori and H. suis, it has been hypothesized that the degradation of Gln and GSH may lead to a deficiency for the host, possibly initiating or promoting several pathologies. Therefore the in vivo effect of oral supplementation with Gln and GSH was assessed. Oral supplementation with Gln was shown to temper H. suis induced gastritis and epithelial (hyper)proliferation in Mongolian gerbils. Astonishingly, supplementation of the feed with GSH, another GGT substrate, resulted in inflammation and epithelial proliferation levels returning to baseline levels of uninfected controls. This indicates that Gln and GSH supplementation may help reducing tissue damage caused by Helicobacter infection in both humans and pigs, highlighting their potential as a supportive therapy during and after Helicobacter eradication therapy.

The effect of FT500 Plus(®) on ovarian stimulation in PCOS women.

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus(®)). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1±0.9 versus 13.5±1; P=0.0001). Group A showed a significant increase in the number of MII oocytes (6.3±2.5 versus 4.5±2; P=0.03) and glutathione peroxidase activity in follicular fluid (15.4±6.2 versus 11±2.2; P=0.04). FT500 Plus(®) may be considered in PCOS patient for improving oocyte quality.

Treatment of dyslipidemia in HIV.

Patients infected with HIV have a high risk of developing dyslipidemia. Effective therapeutic strategies can be challenging due to an increase risk of drug interactions and other comorbidities. Understanding the underlying pathophysiology and the principles of pharmacological and non-pharmacological therapeutic interventions can be of value in the appropriate management of dyslipidemia in the HIV-infected patient.

Monitoring the toxic effects of Pb, Cd and Cu on hematological parameters of Wistar rats and potential protective role of lipoic acid and glutathione.

Heavy metal pollution is a serious environmental and health problem. The negative effects of heavy metals that can enter human body can be reduced by the addition of some supplements. In this study, the effects of lead (Pb), cadmium (Cd) and copper (Cu) on the hematological parameters in Wistar rats in the absence and presence of lipoic acid and glutathione were analyzed. Pb, Cd and Cu intoxication significantly affected the hematological parameters of treated animals. The main effects in the case of Pb and Cd intoxication were decreased values of erythrocytes, hemoglobin and hematocrit (up to 30% and 20% for these two metals, respectively) compared with the control group. Cu intoxication caused decrease in hematocrit, thrombocytes, mean cell volume values (c.a. 15%) and slight decrease in the erythrocyte number, while the value of hemoglobin increased (c.a. 7%). The treatment with lipoic acid and glutathione reduced the toxic effects of these metals in all cases.