Chemical Composition, Nutritional Value, Antioxidative, and In Vivo Anti-inflammatory Activities of Opuntia Stricta Cladode.

The cactus family plant has been used in folk medicine for a long time. In this work, Opuntia stricta chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that O. stricta is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 µg/g), apigenin-7-Glu (3.15 µg/g), and catechin (2.85 µg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. In vivo, the methanol extract from Opuntia stricta showed anti-inflammatory activity. The computational modeling reveals that O. stricta compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both in vitro and in vivo findings. These data indicate that Opuntia stricta cladode powder could be potentially useful in pharmaceutical and food applications.

Oxidative stress in patients with asthma and its relation to uncontrolled asthma.

This study aims to evaluate markers of oxidative stress in Tunisian asthmatic patients and investigate whether their markers are correlated with uncontrolled asthma. This prospective cohort study was conducted on 48 healthy subjects and 60 patients with asthma (34 patients with controlled asthma and 26 patients with uncontrolled asthma). The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in plasma by spectrophotometry. Asthmatic patients have significantly higher plasmatic levels of MDA and AOPP than healthy controls (p < 0.001). Lower GSH level and GPx activity were found in patients with asthma compared to controls (p < 0.001). In contrast, higher SOD activity was noted in asthmatic patients (p < 0.001). The comparison among the patients with controlled asthma and uncontrolled asthma revealed increased MDA and AOPP levels and SOD activity (p < 0.001) as well as a decreased GSH level and GPx activity (p = 0.004, p = 0.019) in patients with uncontrolled asthma. Spirometry level was significantly correlated with SOD activity (r = 0.447; p = 0.010), whereas no significant correlations were found with the other parameters (MDA, AOPP, GSH, and GPx). Asthmatic patients, especially those with uncontrolled asthma, suffer a high degree of reactive oxygen species (ROS) formation causing considerable oxidative stress. Increased MDA level and SOD activity and reduced GPx activity were predictors of poorly controlled asthma.

[Multiple drug hypersensitivity in patients with an allergy to antibiotics]. / Hypersensibilité médicamenteuse multiple chez des patients ayant une allergie aux antibiotiques.

INTRODUCTION: Multiple drug hypersensitivity (MDHS) is defined as confirmed drug hypersensitivity (DHS) to 2 or more drugs that are not chemically related. The objective of our study is to describe the cases of MDHS with antibiotics notified to the regional pharmacovigilance service (SRPV) of Sfax (Tunisia). METHODS: Our study is of a descriptive cross-sectional type, focusing on patients who consulted at the SRPV in Sfax during the period between 2013 and 2020 and who presented at least two episodes of DHS occurring at different times (at least one month apart). RESULTS: In our study, we included 29 patients (18 women and 11 men with a mean age of 59 years) who presented 69 sequential MDHS reactions documented either by a positive re-administration in 29 cases or by allergological exploration in 20 case, or by a highly suggestive clinical history in 20 cases. The frequency of MDHS was 1.13%. The drugs involved in the occurrence of these 69 DHS reactions were antibiotics in 55 cases (80%), antiepileptics in 6 cases (9%), NSAIDs in 4 cases (6%) and other drugs in 4 cases (6%) (one case with allopurinol, one case with strontium ranelate and two cases with gliclazide). CONCLUSION: MDHS pose a real problem of therapeutic management. Indeed, these reactions can lead to a difficult choice of drugs with the impossibility of prescribing optimal first-line therapies.

Primary ciliary dyskinesia associated with multiple drug intolerance syndrome: a case report.

INTRODUCTION: The term multiple drug intolerance syndrome is used for patients who express adverse drug reactions to three or more drugs without a known immunological mechanism. It is a distinct clinical entity, different from cross-reactivity. The symptoms can range from a benign rash to life threatening syndromes like drug reaction with eosinophilia and systemic symptoms. CASE REPORT: We report the case of an 8-year-old child with primary ciliary dyskinesia complicated by bronchiectasis who presented multiple drug intolerance syndrome.Through this observation; we discuss the diagnostic elements of this syndrome. CONCLUSION: In the absence of validated criteria for diagnosing multiple drug intolerance syndrome, a detailed history is essential, especially to identify the warning signs and the risk factors.

Effect of Artichoke (cynara scolymus) on cardiac markers, lipid profile and antioxidants levels in tissue of HFD-induced obesity.

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.

Preventive effect of Artichoke (Cynara scolymus L.) in kidney dysfunction against high fat-diet induced obesity in rats.

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compared to Atorvastatin (ATOR) in the kidney of Wistar rats fed a high-fat diet. The experimental animals were divided into five groups: control (Cont), HFD, HFD treated with EEA (200 mg/kg), HFD treated with EEA (400 mg/kg), and HFD treated with ATOR. Organ weights, lipid profile, renal markers, and antioxidants enzymes were measured. Oral administration of EEA (200 and 400 mg/kg) for 60 days showed a significant decrease in organ weights and kidney markers levels accompanied by decreasing in oxidative stress biomarkers as compared to HFD groups. The histological findings showed a renoprotective effect of artichoke extract. These findings suggest that EEA exerts anti-oxidant kidney effects in HFD- induced obese rats.

Protective effect of Urtica dioica in induced neurobehavioral changes, nephrotoxicity and hepatotoxicity after chronic exposure to potassium bromate in rats.

BACKGROUND AND PURPOSE: Chronic exposure to potassium bromate (KBrO3), a toxic halogen in the environment, has become a global problem of public health. The current study aims to elucidate for the first time the effect of Urtica dioica (UD) on behavioural changes, oxidative stress, and histopathological changes induced by KBrO3 in the cerebellum, kidney, liver and other organs of adult rats. STUDY DESIGN AND METHODS: The rats were divided into four groups: group 1 served as a control received physiological serum, Group 2 received KBrO3 (2 g/L of drinking water), group 3 received KBrO3 and Urtica dioica (100 mg/kg), and group 4 received KBrO3 and Urtica dioica (400 mg/kg). We then measured behavioural changes, oxidative stress, and biochemical and histological changes in the cerebellum, liver, kidney and others organs in these rats. After 30 days of treatment, the animals were sacrificed. RESULTS: We observed significant behavioural changes in KBrO3-exposed rats. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. In addition, it inhibits hepatic and lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP), attenuates KBrO3-mediated enzyme depletion, catalase, superoxide dismutase, glutathione peroxidase enzymatic and antioxidant activities in the liver and kidney. Rats that were co-managed with Urtica dioica at the high portion of 400 mg/kg indicated a higher effect than that treated with the low dose of 100 mg/kg practically in all the tests carried out. CONCLUSION: Our results demonstrate that Urtica dioica is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.

Creation of an adequate animal model of hyperuricemia (acute and chronic hyperuricemia); study of its reversibility and its maintenance.

AIM: Hyperuricemia is defined by the European Rheumatology Society as a uric acid level greater than 6 mg/dl (60 mg/l or 360 µmol/l). Our goal was to evaluate the hypouricemic effect of nettle. For this reason, we have first of all try to create an hyperuricemic animal model which is very suitable because at the level of literature there is not an exact model, there are many models and our objective is to set an adequate model. MATERIALS AND METHODS: An attempt has been made to test acute and chronic hyperuricemia by varying the duration and method of induction of potassium oxonate. Similarly, attempts have been made to induce chronic hyperuricemia through an animal and vegetable diet. The reversibility of hyperuricemia was tested with a maintenance protocol. KEY FINDINGS: For the creation of the hyperuricemia model, it has been shown that acute hyperuricemia cannot be induced by short administration of potassium oxonate and persistent chronic hyperuricemia can be induced only after daily administration of oxonate of potassium by intraperitoneal injection for 15 days. Indeed, hyperuricemia was reversible after stopping the administration of potassium oxonate. The high-purine diet is also capable of inducing chronic hyperuricemia but to a less extent. SIGNIFICANCE: After creating an adequate model of hyperuricemia while setting the dose of potassium oxonate, route of administration and duration. A maintenance protocol was followed which subsequently made it possible to deduce that the daily administration of potassium oxonate must be continued to maintain the hyperuricemia.

Overexpression of P-glycoprotein and resistance to Imatinib in chronic myeloid leukemia patients.

BACKGROUND: The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM. METHOD: The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry. RESULT: Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001). CONCLUSION: The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.

Screening of pharmacological uses of Urtica dioica and others benefits.

BACKGROUND: Natural products, whether pure compounds or standardized plant extracts, offer unlimited opportunities for other drug sources due to the unequaled availability of chemical diversity. Stinging Nettle (Urtica dioica) is a unique herbaceous perennial flowering plant with stinging hairs. The leaf extract of nettle was one of the herbal remedies which the experimental, clinical and trials have complemented each other. It is a very well-known plant with a wide historical background use of stems, leaves and roots. It has a long history of use as power sources such as soup or curry, and also used as fiber and a medicinal plant. Urtica dioica has traditionally been used in the control of cardiovascular disorders especially hypertension. The leaf extract of Urtica dioica has been reported to improve glucose homeostasis in vivo. Nettle root could prevent some of the effects of prostatic hyperplasia. Extracts of nettle leaf are used as anti-inflammatory remedies for rheumatoid arthritis. Urtica dioica extract significantly increased the sensitivity of breast cancer cells to paclitaxel. This article aims to review the very wide ranging of pharmacological effects of Urtica dioica extract. METHODS: Articles on PuBmed between 1980 and 2019. RESULTS: Description and critical review of the pharmacological effects of Urtica dioica and other uses. CONCLUSION: The nettle is actually a plant with many qualities and uses. The interest in it is deserved and it is given by other studies and investigations.

Relationship of oxidative stress in the resistance to imatinib in Tunisian patients with chronic myeloid leukemia: A retrospective study.

BACKGROUND: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM. METHODS: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples. RESULTS: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01). CONCLUSIONS: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H2 O2 has a key role in the resistance to IM treatment.

Polysaccharide from Pimpinella anisum seeds: Structural characterization, anti-inflammatory and laser burn wound healing in mice.

The polysaccharide preparation from Pimpinella anisum seeds (PAP) was isolated and characterized to evaluate its laser burn wound-healing and anti-inflammatory activities in mice. The structure characterization of PAP by Infra-red spectrometry (IR), Nuclear magnetic resonance (NMR), Gas chromatogram-Mass spectrometer (GC-MS) and colorimetric methods revealed an optimum yield of 8.84%, a high quantity of carbohydrate (64.75%) and low levels of lipids, protein and sulfate. Galactose (33.47%), ß-d-Glucose (26.71%) and α-d-Mannose (18.21%) were the major monosaccharides components presenting in PAP, and a smaller amounts of ß-d-Galactose, d-Fructose, α-d-Glucose, α-l-Galactose and arabinose were detected. PAP showed noticeable antioxidant and antibacterial properties. The anti-inflammatory activity of PAP in the carrageenan-induced paw edema model in mice, demonstrated by reduced edema and cellular infiltration, and oxidative stress markers in muscle tissue. A beneficial wound healing effect was also revealed. The topical application of PAP based gel on laser burn lesions accelerates wound contraction, the re-epithelization and remodeling phases after seven days of treatment. The results demonstrated that PAP is a novel promising source of natural wound healing and anti-inflammatory drugs. The high content and varied PAP monosaccharides seem to be responsible for the observed biological activities.

LC-MS/MS Analysis and Hepatoprotective Activity of Artichoke (Cynara scolymus L.) Leaves Extract against High Fat Diet-Induced Obesity in Rats.

Cynara scolymus L. (Artichoke) has been used for the treatment of metabolic disorders. The purpose of the present study was to investigate the hepatoprotective effect of Cynara scolymus leaves extract against a high fat diet (HFD) induced rats. This study investigated the most abundant phenolic compounds rich Cynara scolymus leaves extract and it is antihypercholesterolemic and antioxidative effects in vivo. The hypercaloric high fat diet (HFD) was treated with 200 mg/kg and 400 mg/kg of ethanol extract (EEA) from leaves of Cynara and atorvastatin (ATOR) (10 mg/kg/day) during an 8-week period. Lipid profile was measured and oxidative stress systematic in hepatic tissue was determined. Our data revealed that HFD-induced hepatic dysfunction manifested by significant abnormal levels of AST, ALT, ALP, LDH, and OCT was accompanied by increasing levels of oxidative stress biomarker (ROS, MDA, and AOPP) while decreasing in antioxidant status. Coadministration of EEA significantly reduced serum lipid profile and hepatic disorders which was confirmed to be histological by reducing the fatty liver deposition in hepatic lobule. These findings suggest that Cynara leaves exert antiobesity and antioxidant liver effects in HFD-induced obese rats.

Cytoprotective and antioxidant effects of the red alga Alsidium corallinum against hydrogen peroxide-induced toxicity in rat cardiomyocytes.

CONTEXT: Sepsis is the manifestation of the immune and inflammatory responses to infection that may ultimately result in multiorgan failure. Many substances are involved in myocardial dysfunction in sepsis, including hydrogen peroxide. OBJECTIVE: This study evaluates the protective activity of the red alga Alsidium corallinum against hydrogen peroxide (H2O2)-induced toxicity in H9c2 cardiomyocytes. MATERIAL AND METHODS: The biological properties of A. corallinum were firstly investigated. Secondly, the H9c2 cells were pre-treated with alga extract, and then exposed to H2O2. RESULTS: Our results showed richness of the alga in antioxidant compounds, and its biological activities. H2O2 induced a morphological changes and decrease in H9c2 cell viability correlating with an increase in enzymatic and non-enzymatic antioxidants. Pre-treatment with A. corallinum, reduces toxicity and decreased the antioxidants status induced by H2O2. CONCLUSION: These findings indicated for the first time the protective effect of A. corallinum against H2O2-induced toxicity in H9c2 cells.

Sulfated polysaccharide isolated from Globularia alypum L.: Structural characterization, in vivo and in vitro anticoagulant activity, and toxicological profile.

A sulfated polysaccharide from Globularia alypum L. (GASP) was extracted with a yield of 14.2%. GASP is composed mostly of sulfate and total sugars (13.29% and 71.56%, respectively) with small amount of proteins and lipids. The chemical and structural characterization was studied by Infra-Red spectroscopic and gas chromatography-mass spectrometry (GC-MS). GASP composed of eight carbohydrates where galactose, glucose, and mannose are the major compounds (33.47%, 26.71% and 18.21%, respectively). The in vitro and in vivo anticoagulant activities in rats were tested using the standard coagulation assays activated partial thromboplastin time (aPTT), prothrombine time (TT) and thrombin time (PT) tests. Both doses of GASP (200 and 500 mg/kg b.w) displayed a significant in vitro (1.22 and 1.33-fold, 1.17 and 1.27-fold, and 1.21 and 1.26-fold, respectively) and in vivo (1.47 and 2.52-fold; 1.20 and 1.43-fold; 1.21 and 1.40-fold, respectively) compared with the control. Toxicity studies on liver performed by the catalytic activity of transaminases in plasma, oxidative stress markers and hepatic morphological changes indicated that GASP at both doses are not toxics. The important pharmacological and toxicological profile of GASP revealed that this compound may be used as a novel and effective drug.

Combined use of Vitamins E and C improve nephrotoxicity induced by colistin in rats.

This study was performed to investigate the protective effect of combined use of Vitamins E and C on colistin-induced tubular damage in rat. Animals were treated with sterile saline, colistin methanesulfonate (CMS), CMS + Vitamin E + Vitamin C, and Vitamin E + vitamin C, respectively, for seven days. Thereafter, animals were sacrificed and the urine N-acetyl-b-D-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) levels, plasma level of creatinine (Cr), vitamin E and vitamin C, and renal tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as renal histology were performed. CMS induced acute tubular necrosis, increased the NAG, GGT, and MDA levels, and reduced the Vitamin E, Vitamin C, SOD, CAT, and GPx activities. Co-treatment with vitamins E and C restored all biochemical parameters cited above and improved the histopathological damage. Tubular damage induced by colistin is at least partly due to oxidative stress. Nephroprotective effect of Vitamins E and C is partially mediated through its antioxidant properties, and the higher protection by the combination of these vitamins is related to its synergistic effects.

Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia.

BACKGROUND: Methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy, but it is associated with serious toxicities in a considerable number of patients. OBJECTIVES: The aim of the current study was to determine which variables were associated with MTX toxicity in children, adolescents and young adults with ALL. MATERIAL AND METHODS: In this prospective study, 35 patients with newly diagnosed ALL, treated according to the 58951 European Organization for Research and Treatment of Cancer - Children's Leukemia Group (EORTC-CLG) protocol, were prospectively enrolled. Toxicity data was collected objectively after each high-dose methotrexate (HD-MTX) course. The risk factors of MTX toxicity were determined using multiple linear regression analysis, with age, gender, immunophenotype, risk group, plasma MTX levels, plasma homocysteine (HCY) levels, and MTHFR C677T included as independent variables. RESULTS: Twenty-five (71.4%) patients experienced toxicity on at least 1 course of HD-MTX. In the univariate linear regression, the global toxicity score was associated with a significant rise in plasma HCY concentrations within 48 h after MTX administration (ß = 0.4; R2 = 0.12; p = 0.02). In the multiple regression model, the global toxicity score was significantly associated with a higher MTX plasma levels at 48 h (ß = 0.5; R2 = 0.38; p = 0.001) and CT 677 MTHFR genotype (ß = 0.3; R2 = 0.38; p = 0.01). CONCLUSIONS: Routine monitoring of plasma MTX concentrations is essential to detect patients at a high risk of MTX toxicity. MTHFR C677T genotyping may be useful for predicting MTX toxicity.