Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Metabolic syndrome; Definition, Pathogenesis, Elements, and the Effects of medicinal plants on it's elements.

Introduction: Metabolic syndrome (MetS) is a cluster of metabolic risk factors that include central obesity, hypertension, insulin resistance, and atherogenic dyslipidemia and is strongly associated with a greater risk for developing cardiovascular disease and type 2 diabetes mellitus. Methods: A literature search was conducted using the words metabolic syndrome, definition and pathogenesis in Scopus, and PubMed. The search also extended to cover medicinal plants and their role as a potential treatment of the metabolic syndrome. The search based on studies published in the English language from 1st of January 2000 to 30th of May 2021. The abstracts and the articles were then screened. Articles were scanned and read; further relevant references in the reference lists are also included. Results: Both lifestyle factors and genetic factors are involved in the pathogenesis of the metabolic syndrome. Recently, MetS have gained significant attention due to the high prevalence of obesity worldwide. Diagnosis of patients with MetS is important to improve the outcomes of the disease by employing lifestyle and risk factors modifications. Currently, there is a rising interest in medicinal plants and their extracts because the medicinal plants have minimal side effects. Here we review the history, definitions, pathogenesis, management of metabolic syndrome and summarize the beneficial effects of some medicinal plants and their extracts on MetS. Conclusion: Further research and clinical studies are needed to establish whether medicinal plants can be safely given as potential therapy for metabolic syndrome and whether this can be beneficial in low resources setting countries.

Correction to: Metabolic syndrome; Definition, Pathogenesis, Elements, and the Effects of medicinal plants on it's elements.

[This corrects the article DOI: 10.1007/s40200-021-00965-2.].

Effect of Acacia senegal on TGF-ß1 and vascular mediators in a rat model of diabetic nephropathy.

CONTEXT: Transforming growth factor-ß1 (TGF-ß1), endothelin-1 and angiotensin II are responsible for extracellular matrix accumulation within the kidney in diabetic nephropathy. OBJECTIVE: This study evaluated the effect of adding Gum Arabic (GA) and insulin on serum glucose, renal function, TGF-ß1, endothelin-1, and angiotensin II in rats with diabetic nephropathy. METHODS: Sixty male Sprague-Dawley rats were divided into; normal, normal plus GA, diabetic rats (DM), DM plus insulin, DM plus GA, and DM plus insulin plus GA groups. Levels of glucose and creatinine in serum, TGF-ß1, angiotensin II, and endothelin-1 in renal homogenate and HbA1c were measured. RESULTS: Serum creatinine, TGF-ß1, angiotensin II, and endothelin-1 were increased in diabetic rats. GA decreased serum glucose, TGF-ß1, angiotensin II, endothelin-1, and HbA1c in diabetic rats. GA and insulin decreased serum glucose, creatinine, TGF-ß1, angiotensin II, endothelin-1, and HbA1c in diabetic rats. CONCLUSION: Co-administration of GA with insulin to rats with diabetic nephropathy improved the glycemic state, renal function, TGF-ß1, endothelin-1, and angiotensin II.

Dietary Fibers (Gum Arabic) Supplementation Modulates Hepatic and Renal Profile Among Rheumatoid Arthritis Patients, Phase II Trial.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects the synovial joints with systemic manifestations. RA has a major impact on liver and kidney functions as part of the disease pathogenesis or as a sequel of disease medications or, mostly, both of them. The kidney and liver involvement increases the RA morbidity and mortality. Nowadays, dietary interventions are proposed as potential modifiers for disease severity. Gum Arabic (GA) is acacia senegal exudates; it is soluble fiber with prebiotic properties. GA has been discovered to be protective against experimental nephrotoxicity and hepatotoxicity, with comparable findings in human studies. This article addresses the effect of GA on hepatic and renal profile among RA patients. Methods: Forty patients aged 18-70 received GA daily for 12 weeks as a single dose of 30 g. The liver enzymes, total protein level, serum albumin, serum globulin level, urea, creatinine, and serum electrolytes have been measured as a baseline after 4 weeks and by the end of the study. Cobas C311 (Roche, Germany) automated chemistry analyzer directly determined the values for total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine. The study ethically has been approved by the Ethical Committee of the National Medicines and Poisons Board. Trial Registration Identifier: NCT02804581. Results: Regarding the liver enzymes, GA has significantly decreased the liver enzymes apart from alkaline phosphatase, which showed no significant change. In contrast, GA has increased the serum albumin level with a minor impact on the serum globulin level. Furthermore, GA has also significantly decreased the level of urea (P = 0.0001) and level of Sodium (P = 0.002) with nonsignificant change on creatinine and potassium concentrations. Conclusion: GA presents hepatic and renal protective effects among RA patients, evidenced by the significant reduction of urea and liver enzymes. Thus, it can be recommended as a dietary supplement for RA patients. Nonetheless, we recommend further investigation to support our findings.

Potential Role of Acacia Senegal (Gum Arabic) as Immunomodulatory Agent among newly diagnosed COVID 19 Patients: A structured summary of a protocol for a randomised, controlled, clinical trial.

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Gum Arabic (Acacia Senegal) Augmented Total Antioxidant Capacity and Reduced C-Reactive Protein among Haemodialysis Patients in Phase II Trial.

BACKGROUND: Oxidative processes might increase in patients with end-stage renal disease (ESRD) according to the current literature. Oxidative stress (OS) is a risk factor of atherosclerosis and cardiovascular complications, which are major causes of mortality among ESRD patients. Haemodialysis (HD) is life-saving procedure, nevertheless it is an active chronic inflammatory status that could augment cardiovascular disease and increase mortality. Gum Arabic (GA) has been claimed to act as an antioxidant and anti-inflammatory agent in experimental studies and clinical trials. Therefore, we assumed GA supplementation among haemodialysis patients would reduce oxidative stress and consequently reduce the state of chronic inflammatory activation associated with haemodialysis. METHODS: Forty end-stage renal failure (ESRF) patients aged 18-80 years who were on regular haemodialysis in Arif Renal Center, Omdurman, Sudan, were recruited. All recruited patients met the inclusion criteria and signed informed consent prior to enrolment. The patients received 30 g/day of GA for 12 weeks. C-reactive protein (CRP) and complete blood count (CBC) were measured as baseline and monthly. Total antioxidant capacity (TAC) and oxidative stress marker malondialdehyde (MDA) levels were measured before and after GA intake. Ethical approval from the National Medicines and Poisons Board was obtained. RESULTS: Gum Arabic significantly augmented total antioxidant capacity level (P < 0.001) (95% CI, 0.408-0.625) and also attenuated oxidative marker MDA and C-reactive protein (P < 0.001). CONCLUSIONS: GA has revealed potent antioxidative and anti-inflammatory properties in haemodialysis patients. Oral digestion of GA (30 g/day) decreased oxidative stress and inflammatory markers among haemodialysis patients. Trial registration. ClinicalTrials.gov Identifier: NCT03214692, registered 11 July 2017 (prospective registration).

Comparison of the effectiveness of lectures based on problems and traditional lectures in physiology teaching in Sudan.

BACKGROUND: Lectures are one of the most common teaching methods in medical education. Didactic lectures were perceived by the students as the least effective method. Teaching methods that encourage self-directed learning can be effective in delivering core knowledge leading to increased learning. Problem based learning has been introduced as an active way of learning but it has some obstacles in developing countries where the intake is huge with minimum resources. This study introduces a new teaching approach: lectures based on problems (LBP) and evaluates their effectiveness compared to traditional lectures (TL) in physiology teaching. METHODS: LBP and TL were applied in physiology teaching of medical students at University of Science and Technology during their study of introduction to physiology and respiratory physiology courses. Equal number of lectures was given as LBP and as TL in each course. Students were given quizzes at the end of each course which were used to compare the effectiveness of the two types of lectures. A questionnaire was used to assess students' satisfaction about LBP and the perceived effects of the two methods on the students' attitude and practice towards learning physiology. RESULTS: In LBP the students have better attention (P = 0.002) and more active role (P = 0.003) than in TL. Higher percentage of students think that LBP stimulated them to use references more (P = 0.00006) and to use the lecture time more effectively (P = 0.0001) compared to TL. However, there was no significant difference between LBP and TL in the awareness of the learning objectives. About 64% of students think that LBP is more enjoyable and it improved their understanding of physiology concepts. Comparison of the students' quiz marks showed that the means of the students' marks in the introduction to physiology and respiratory courses were higher in the quizzes of LBP than in TL with a significant difference between them ((P = .000), (P = .006) respectively. CONCLUSIONS: LBP improved students' understanding of physiology concepts and increased students' satisfaction about physiology learning. LBP achieved some of the objectives of PBL with the minimum resources and it can be used to improve the effectiveness of the lectures.

Acacia Senegal (Gum Arabic) Supplementation Modulate Lipid Profile and Ameliorated Dyslipidemia among Sickle Cell Anemia Patients.

BACKGROUND: Sickle cell disease (SCD) is an inherited haemolytic anemia with a variable course and severity. Knowledge of prognostic biomarkers may help in the establishment of therapeutic intervention, management, and follow-up of patients. There have been scattered reports of low high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) in SCD patients. In addition, TG levels have been suggested to be elevated in patients with increased endothelial activation. An increased TG level has been associated with haemolysis, vascular dysfunction, and increased prevalence of pulmonary hypertension. Gum Arabic (GA) is an edible, dried, gummy exudate from the acacia Senegal tree. Several studies on GA ingestion have shown reduced plasma cholesterol and low-density lipoprotein (LDL) concentrations in both animals and humans. We investigated GA's therapeutic potential to modulate serum lipids in patients with sickle cell anemia. METHODS: This study recruited and documented secondary outcomes in 47 patients (aged 5-42 years) carrying hemoglobin SS. The patients received 30 g/day of GA for 12 weeks. Total cholesterol, TG, LDL, and HDL were measured before and after GA intake. Cobas C311 (Roche, Germany) automated chemistry analyser was used for direct determination of the values of the lipid profile. RESULTS: GA significantly decreased total cholesterol (TC), TG, and LDL (p = 0.006, 0.04, and 0.02, resp.). GA showed no effect on HDL level. Baseline serum TG and LDL correlated significantly with the hydrogen peroxide (H2O2) level, which is known as an oxidative stress marker (p = 0.003 and 0.04, resp.). None of the lipid profile elements correlated with age. CONCLUSION: Our results revealed that dyslipidemia in sickle cell patients is associated with oxidative stress but not associated with age. The findings showed that GA significantly decreased TC, LDL, and TG levels, revealing a novel effect of GA, which is considered a natural dietary fibre that can modulate lipid profile in patients with sickle cell anemia. TRIAL REGISTRATION: This retrospective trial is registered with ClinicalTrials.gov Identifier: NCT02467257 on 3 June, 2015.

Oxidative stress-induced senescence markedly increases disc cell bioenergetics.

Cellular senescence is a phenotype characterized by irreversible growth arrest, chronic elevated secretion of proinflammatory cytokines and matrix proteases, a phenomenon known as senescence-associated secretory phenotype (SASP). Biomarkers of cellular senescence have been shown to increase with age and degeneration of human disc tissue. Senescent disc cells in culture recapitulate features associated with age-related disc degeneration, including increased secretion of proinflammatory cytokines, matrix proteases, and fragmentation of matrix proteins. However, little is known of the metabolic changes that underlie the senescent phenotype of disc cells. To assess the metabolic changes, we performed a bioenergetic analysis of in vitro oxidative stress-induced senescent (SIS) human disc cells. SIS disc cells acquire SASP and exhibit significantly elevated mitochondrial content and mitochondrial ATP-linked respiration. The metabolic changes appear to be driven by the upregulated protein secretion in SIS cells as abrogation of protein synthesis using cycloheximide decreased mitochondrial ATP-linked respiration. Taken together, the results of the study suggest that the increased energy generation state supports the secretion of senescent associated proteins in SIS disc cells.

Biochemical effects and safety of Gum arabic (Acacia Senegal) supplementation in patients with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is a hereditary chronic hemolytic anemia with several clinical consequences. Intravascular sickling of red blood cells leads to multi-organ dysfunction. Moreover, several biochemical abnormalities have been associated with SCA. Gum arabic (GA) is an edible dried gummy exudate obtained from Acacia Senegal tree. GA showed antioxidant and cytoprotective activities and demonstrated protection against hepatic, renal, and cardiac toxicities in experimental rats. We hypothesized that regular intake of GA improves renal and liver functions in patients with SCA. METHODS: Forty-seven patients (5-42 yr) carrying hemoglobin SS were recruited. The patients received 30 g/day GA for 12 weeks. Blood samples were collected before administering GA and then after 4, 8, and 12 weeks. Liver enzymes, total protein, albumin, electrolytes, urea, creatinine, and uric acid were determined in the serum. The study was approved by the Al Neelain University Institutional Review Board and Research Ethics Committee Ministry of Health. The trial was registered at ClinicalTrials.gov (identifier: NCT02467257). RESULTS: GA significantly decreased direct bilirubin level [statistical significance (P-value)=0.04]. It also significantly decreased serum alanine transaminase level after 4 weeks, which was sustained till the 8th week. GA, however, had no effect on serum aspartate transaminase level. In terms of renal function, GA decreased serum urea level but the effect was not sustained after the first month. CONCLUSION: GA may alter the disease severity in SCA as demonstrated by its ability to decrease direct bilirubin and urea levels in the serum.

Toll Like Receptor-4 Gene Polymorphism and Susceptibility to Pulmonary Tuberculosis.

Tuberculosis (TB) affects human life globally for a long time. The difference in clinical outcome of infection suggests that host genetic makeup is responsible for such variability. Toll like receptors (TLRs) are pattern recognition receptors and have a significant role in mycobacterial recognition by the innate immune system. TLR-4 is the key receptor in initiation of innate immunity against M. tuberculosis. This study investigated whether variants in TLR-4 896A/G (Asp299Gly) and TLR-4 1196C/T (Thr399Ile) genes are related with susceptibility or resistance to pulmonary tuberculosis (PTB) in Saudi population. Genotyping of TLR-4 896A/G, TLR-4 1196C/T gene was performed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR -RFLP) in 60 PTB patients and 60 control subjects. The A allele at (896A/G) was more frequent in the control group while G allele was more common in PTB patients. The frequency of T allele of (1196C/T) polymorphism was significantly increased in PTB patients as compared to the control group (P < 0.001; Odds ratio (OR) 2.79, 95% Confidence interval (CI) 1.65-4.72). A trend toward increased frequency of TT and CT genotypes of TLR4 at (1196C/T) were also observed in PTB patients as compared to control group (48.3% vs. 26, 7%, and 21.7% vs. 15%), respectively. This study suggests that that TLR4 polymorphism especially TLR4 rs4986791 may be associated with increase susceptibility to pulmonary tuberculosis, and C allele of rs4986791 is a promising protective factor for tuberculosis susceptibility in Saudi population.

Gum Arabic Fibers Decreased Inflammatory Markers and Disease Severity Score among Rheumatoid Arthritis Patients, Phase II Trial.

BACKGROUND: Rheumatoid arthritis (RA) is autoimmune inflammatory disease that attacks the synovium of the joints. Both TNFa and interleukin-1 play crucial roles in the pathogenesis of RA. Gum Arabic (GA) is gummy exudates from Acacia senegal tree. Gum Arabic fermentation by colonic bacteria increases serum butyrate concentrations, so it is considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through its derivative butyrate. To the best of our knowledge, this is the first study conducted to investigate GA intake on inflammatory markers among RA patients. PATIENTS AND METHODS: This is clinical trial phase II in which 40 patients were enrolled aged 18 to 70 years. Patients received 30g/day GA for 12 weeks. TNF α, ESR, and complete blood count were measured and DAS-28 was calculated before and after regular GA consumption. Study was approved by the Ethical committee of National Medicines and Poisons Board. RESULTS: This study showed significant decrease in level of serum TNF α (p value 0.05) [95% CI, 0.65 -16.5], ESR (p value 0.011) [95% CI, 2.6 -18.89], and number of swollen and tender joints in RA patients after 12 weeks of GA intake which reflected as significant decrease in disease severity score DAS 28 P.V:0.00 [95% CI, 1.25 -1.99]. On the other hand, GA had trivial change in blood indices. CONCLUSION: Gum Arabic has favorable immune modulator effect on rheumatoid arthritis. It can be utilized in clinical practice as adjuvant therapy. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov Identifier: NCT02804581 Registered at 19 June 2016, prospective registration.

Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial.

BACKGROUND: There is a strong association between cardiometabolic risk and adipose tissue dysfunction with great consequences on type 2 diabetic patients. Visceral Adiposity Index (VAI) is an indirect clinical marker of adipose tissue dysfunction. Gum Arabic (GA) is a safe dietary fiber, an exudate of Acacia Senegal. Gum Arabic had shown lipid lowering effect in both humans and animals. The aim of this trial was to determine the effect of GA supplementation on anthropometric obesity marker, Visceral Adiposity Index (VAI) and blood pressure in patients with type 2 diabetes mellitus. METHODS: This randomized, double blinded, placebo controlled trial recruited a total of 91 type 2 diabetic patients (73 females, 18 males), age (mean ± SD) 50.09 ± 9.3 years on hypoglycemic agents and were randomly assigned into two groups, either to consume 30 g of GA or 5 g of placebo daily for 3 months. Anthropometric obesity markers were measured and indices were calculated. Blood pressure was measured and high density lipoprotein (HDL) and triglycerides (TG) were determined in fasting blood samples at the start and end of the study period. RESULTS: After intervention, Gum Arabic decreased BMI and VAI significantly (P < 0.05) in GA group by 2 and 23.7% respectively. Body adiposity index significantly decreased by 3.9% in GA group while there were no significant changes in waist circumference or waist-to-hip ratio (WHR). Systolic blood pressure significantly decreased by 7.6% in GA group and by 2.7% in placebo group from baseline with no significant changes in diastolic blood pressure in the two groups. CONCLUSION: Gum Arabic consumption at a dose of 30 g/d for 3 months may play an effective role in preventing weight gain and modulating adipose tissue dysfunction in type 2 diabetic patients, although no effect has been shown in waist-to-hip ratio. TRIAL REGISTRATION: The trial had been registered as prospective interventional clinical trials in the Pan African Clinical Trial Registry (PACTR) PACTR201403000785219 , on 7th March 2014.

Gum Arabic as novel anti-oxidant agent in sickle cell anemia, phase II trial.

BACKGROUND: Sickle cell anemia patients suffer from oxidative stress due to chronic inflammation and self-oxidation of sickle hemoglobin (Hb S). Chronic oxidative stress contributes to endothelial dysfunction, inflammation and multiple organ damage in sickle cell disease (SCD). Thus, antioxidant medication may favorably influence the disease. Gum Arabic (GA), edible, dried, gummy exudates from Acacia Senegal tree, has been claimed to act as an anti-oxidant and cytoprotective agent, protecting against experimental hepatic, renal and cardiac toxicities in rats. We hypothesized that regular intake of GA increases anti-oxidant capacity and reduce oxidative stress. METHODS: Forty-seven patients (5-42 years) carrying hemoglobin SS were recruited. Patients received 30 g/day GA for 12 weeks. Total anti-oxidant capacity (TAC), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were measured by spectrophotometric methods before and after GA intake. Complete blood count was measured by sysmex. RESULTS: Gum Arabic significantly increased TAC level P < 0.001and decreased the oxidative markers MDA (P < 0.05) and H2O2 (P < 0.005). CONCLUSIONS: GA has potent anti- oxidative properties in sickle cell anemia. The anti-oxidant effect of GA may thus favorably influence the clinical condition of this and further diseases characterized by oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015. Retrospective registration.

Systemic Lupus Erythmatosus is Associated with Disturbed Cytokine Milieu and Increased TNF-Related Apoptosis-Induced Ligand Levels.

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is cytotoxic to a wide variety of transformed cells, but not to most normal cells. This study measures serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and 10 and soluble TRAIL (sTRAIL) in patients with SLE and assesses their relation to severity of the disease. The study included 70 SLE patients and 20 healthy controls. Patients were diagnosed according to criteria proposed by the American Rheumatism Association for classification of SLE and disease activity was scored using the British Isles Lupus Assessment Group (BILAG-2004). All study participants were subjected to estimation of TNF-α, IL-6, IL-10 and sTRAIL using ELISA. Results revealed that mean disease duration was 6.5±1.5 years, mean BILAG score was 18.2±12.1, while 15 patients (21.4%) had quiescent disease. Blood levels of C3 and C4 and leucocytic count showed progressive decrease, while serum C-reactive protein and anti-double strand DNA antibodies levels showed marked increase with increased disease activity. Five patients (7.1%) were neutropenic. Serum levels of sTRAIL and IL-6 were significantly (P>0.05) higher in patients (1113.5±294 ng/ml and 60±21.5 ng/ml, respectively) than controls (354.7±47.2 ng/ml and 15.6±3.3 ng/ml, respectively) and in patients had active (1157±317 ng/ml and 64.3±20.7 ng/ml, respectively) versus patients had quiescent disease (965.4±115 ng/ml and 45.4±18 ng/ml, respectively). Serum levels of TNF-α were significantly (P>0.05) higher in patients (2.4±0.7 ng/ml) especially those with active (2.8±2 ng/ml) disease compared to controls (1.45±0.9 ng/ml). Patients with quiescent disease showed non-significantly higher TNF-α level (1.52±0.5 ng/ml) as compared to control, but significantly lower than patients with active disease. Serum levels of IL-10 were significantly lower in total patients (2.4±0.7 ng/ml) and patients with active disease (2.33±0.7) as compared to control (2.61±0.6 ng/ml) with a non-significantly (P>0.05) higher levels in patients with quiescent disease (2.61±0.6 ng/ml) than patients with active disease. Estimated serum sTRAIL, TNF-α and IL-6 levels showed positive significant correlation with calculated BILAG activity score, while estimated serum IL-10 levels showed negative significant correlation with activity score. In conclusion, SLE is associated with disturbed levels of serum cytokines and sTRAIL. These disturbances may underlie pathogenesis and/or activation of SLE as BILAG-2004 numeric scoring system significantly correlated with estimated levels of serum cytokines and sTRAIL.

SPAK Sensitive Regulation of the Epithelial Na Channel ENaC.

BACKGROUND/AIMS: The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na(+),K(+),2Cl(-) cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na(+) channel (ENaC). METHODS: ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active (T233E)SPAK, WNK insensitive (T233A)SPAK or catalytically inactive (D212A)SPAK, and ENaC activity estimated from amiloride (50 µM) sensitive current (Iamil) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine Iamil in colonic tissue from wild type mice (spak(wt/wt)) and from gene targeted mice carrying WNK insensitive SPAK (spak(tg/tg)). RESULTS: Iamil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes Iamil was significantly increased following coexpression of wild-type SPAK and (T233E)SPAK, but not following coexpression of (T233A)SPAK or (D212A)SPAK. Colonic Iamil was significantly higher in spak(wt/wt) than in spak(tg/tg) mice. CONCLUSION: SPAK has the potential to up-regulate ENaC.

Oxidative/nitrosative stress in rats subjected to focal cerebral ischemia/reperfusion.

BACKGROUND: Ischemic stroke usually initiates inflammation and oxidative/nitrosative stress leading to neuronal death. AIM: To investigate the existence of oxidative/nitrosativestress in rats subjected to focal cerebral ischemia/reperfusion and its effects on the consequent neurological deficits. MATERIAL AND METHOD: Experimental procedures were performed on 30 adult males Wister rats. In the test group, transient focal cerebral ischemia was induced in 15 rats by occlusion of the left common carotid artery (CCA) for 30 minutes followed by reperfusion for 24 hours. Another 15 rats underwent the surgery at the same neck region without occlusion of CCA and served as a control group. Neurobehavioral tests were evaluated, the levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) metabolites were measured in the serum and brain tissue to detect the effect of surgery on in each group. RESULT: The serum and brain tissue levels of MDA and NO in the test group were significantly higher compared to the control group (P < 0.001). In contrast, serum and brain tissue levels of TAC of rats subjected to ischemia reperfusion was significantly lower compared to the sham operated rats (P < 0.001). Neurological deficit of the test group correlated positively with serum TAC (CC = 0.937, P = 0.000) and brain tissue TAC (CC = 0.949, P = 0.000) and negatively with serum MDA (CC = -0.949, P = 0.000), brain tissue MDA (CC = -0.963, P = 0.000), serum NO (CC = -0.942, P = 0.000) and brain tissue NO (CC = -0.952, P = 0.000). CONCLUSION: The study provided further evidence for the presence of oxidative/nitrosative stress in rats subjected to cerebral ischemia/reperfusion and demonstrates a relationship between oxidative/nitrosative biomarkers and the consequent neurological deficits.

Gum Arabic as fetal hemoglobin inducing agent in sickle cell anemia; in vivo study.

BACKGROUND: High levels of fetal haemoglobin (HbF) decrease sickle cell anaemia (SCA) severity and leads to improved survival. According to in vivo and in vitro studies, butyrate increases HbF production. Its utilization in clinical practice is hampered, however, by its short half-life. Serum butyrate concentrations could be enhanced by colonic bacterial fermentation of Gum Arabic (GA), edible, dried, gummy exudates from Acacia Senegal tree. We hypothesized that regular intake of GA increases serum butyrate levels, thus inducing HbF production and ameliorating symptoms of sickle cell anemia. METHODS: Fourty seven patients (5-42 years) carrying hemoglobin SS were recruited from April 2014 to January 2015. Patients received 30 g/day GA for 12 weeks. HbF, blood count and erythropoietin level were measured. The main outcome of interest was the level of HbF after 12 weeks. The secondary outcomes were improvement in clinical and laboratory results. The study was ethically approved by Alneelain University IRB. RESULTS: The study revealed significant increase in HbF level P.V0.000 [95 % CI, 0.43-1.02], MCV P.V:000 [95 % CI, 2.312-6.058] and Hematocrit level P.V:0.026 [95 % CI, 0.124-1.902]. No significant difference was encountered in platelets count P.V: 0.346 [95 % CI,-25.76-71.94], and WBCs count P.V:0.194 [95 % CI,-8.035-1.68]. Thirty seven percent of patients experienced minor side effects which resolved within a week. CONCLUSION: These findings reveal a novel effect of GA, which may be used to foster fetal hemoglobin production. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015.

Role of N-Nitro-L-Arginine-Methylester as anti-oxidant in transient cerebral ischemia and reperfusion in rats.

BACKGROUND: Previous reports assessing the neuroprotective role of nonselective Nitric Oxide synthase (NOS) inhibitor N-nitro-L-arginine-methylester (L-NAME) following cerebral ischemia/reperfusion are contradictory. The aim of this work was to examine the potential benefits of L-NAME on rats subjected to transient focal cerebral ischemia/reperfusion. METHODS: The study involved 30 adult male Wistar rats divided into three groups 10 rats in each: First group was sham-operated and served as a control, a ischemia/reperfusion (I/R) group of rats infused with 0.9% normal saline intraperitoneally 15 minutes prior to 30 minutes of left common carotid artery (CCA) occlusion and a test group infused with L-NAME intraperitoneally 15 minutes prior to ischemia. Neurobehavioral assessments were evaluated and quantitative assessment of malondialdehyde (MDA), Nitric oxide (NO) metabolites and total antioxidant capacity (TAC) in both serum and the affected cerebral hemisphere were achieved. RESULTS: Rats' neurological deficit and TAC were significantly decreased while NO and MDA were significantly increased in the I/R compared with the control group (P < 0.001). Alternatively in the L-NAME group, neurological deficit and TAC were significantly improved while NO and MDA were significantly decreased compared to I/R group (P < 0.001). CONCLUSIONS: L-NAME pretreatment for rats undergoing cerebral ischemia/reperfusion significantly improves neurological deficit while reducing oxidative stress biomarkers in the affected cerebral hemisphere.