Said S Moselhy

Hepatoprotective effect of Cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats

Cinnamon is used to flavor most foods in Arabian countries. The aim of this study was to evaluate the medicinal importance, reflecting an important trend in research. The hepatoprotective activity of aqueous and ethanolic extracts of cinnamon was investigated against carbon tetrachloride (CC1(4)) induced lipid peroxidation and hepatic injury in rats. The elevated serum AST and ALT enzymatic activities induced by CC1(4) were significantly restored to near normal by oral administration of 200 mg/kg of either extracts once daily for 7 days, as compared to untreated rats. There was a significant elevation in the level of liver malondialdhyde (MDA), while the activities of antioxidant enzymes superoxide dismutase and catalase (SOD and CAT) were significantly decreased in CC1(4) intoxicated rats. The results obtained indicated that ethanolic extract has more potent hepatoprotective action than water extract against CC1(4) by lowering the MDA level and elevating antioxidants enzymes activities (SOD and CAT). The possible mechanism of this activity may be free radical-scavenging polyphenol compounds. The hepatoprotective properties were documented by the histopathological data obtained. Consequently, this extract can be used as a therapeutic regime in treatment of some hepatic disorders without any side effects. Further study will be done for separation and identification of active components and for testing antitumor activity.

Studies on antiretroviral drug concentrations in breast milk: validation of a liquid chromatography-tandem mass spectrometric method for the determination of 7 anti-human immunodeficiency virus medications.

Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers. Using 200 μL of human breast milk, simultaneous quantification of lamivudine (3TC), stavudine (d4T), zidovudine (ZDV), nevirapine (NVP), nelfinavir (NFV), ritonavir, and lopinavir was validated over the range of 10-10,000 ng/mL. Intraday accuracy and precision for all analytes were 99.3% and 5.0 %, respectively. Interday accuracy and precision were 99.4 % and 7.8%, respectively. Cross-assay validation with UV detection was performed using clinical breast milk samples, and the results of the 2 assays were in good agreement (P = 0.0001, r = 0.97). Breast milk to plasma concentration ratios for the different antiretroviral drugs were determined as follows: 3TC = 2.96, d4T = 1.73, ZDV = 1.17, NVP = 0.82, and NFV = 0.21.

Protective effect of vitamin E and epicatechin against nicotine-induced oxidative stress in rats

Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases. Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples and chocolate. It has been reported that tea extracts and/or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. Vitamin E is a major lipid-soluble antioxidant vitamin and free radical scavenger, presents as an integral component of cellular membranes and has important biological functions. The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties. The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats. Results obtained indicated that there was a significant elevation in the levels of malondialdhyde (MDA) in nicotine injected rats. The combined treatment (epicatechin + Vit E) group showed a potential reduction of these parameters more than individual treatment. The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats. In nicotine group, a negative significant correlation between reduced glutathione and MDA (r = −0.92) was observed. In conclusion, these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine-induced carcinogenesis.

The protective effect of epicatchin against oxidative stress and nephrotoxicity in rats induced by cyclosporine

Cyclosporine A (CyA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Reactive oxygen species (ROS) can attack all types of macromolecules including DNA and damage it. Epicatechin (EC) is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples, and chocolate. The goal of this study was to evaluate the protective effect of EC against CyA toxicity and its antioxidant activity in transplanted patients to avoid its side effects. Results obtained showed that, CyA exert its toxic effect by increasing the free radicals and ROS that causes lipid peroxidation and cell damage, this is detected by elevation of hydroperoxides and thiobarbituric acid reactive substances, while the activities of antioxidant enzymes include (superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx]) were significantly decreased as compared with control rats. The deleterious toxic effects of CyA are, at least in part, due to increased production of free radicals and ROS. Treatment of rats with epicatchin ameliorates the toxicity of CyA by decreasing the lipid peroxidation and enhanced the antioxidants enzyme activities.

Synergistic effect of lycopene and tocopherol against oxidative stress and mammary tumorigenesis induced by 7,12-dimethyl[a]benzanthracene in female rats

Breast cancer is one of the most serious problems in oncology. We investigated the antitumor potential of lycopene (Lyco) alone or combined with tocopherol (Lyco + Toco) for 90 days against a single oral dose of (50 mg/kg body weight) 7,12-dimethyl[a]benzanthracene (DMBA)-induced oxidative stress and mammary carcinogenesis in female rats. The treatment protocol started from the day immediately after DMBA administration. Results obtained indicated that there was a significant elevation in the levels of malondialdehyde (MDA) and nitric oxide (NO) in serum and breast tissues of DMBA-injected rats. The combined treatment (Lyco + Toco) group showed a potential reduction of these parameters more than Lyco alone group. The activities of superoxide dismutase, catalase, and glutathione peroxidase were found to be significantly higher when compared to rats treated with Lyco alone. In DMBA group, a positive significant correlation between NO and MDA (r = 0.92) was observed. Histopathological examination revealed the formation of tumor and angiogenesis in DMBA-induced rats and these abnormal changes were ameliorated by combined treatment with Lyco + Toco. In conclusion, these results suggested that supplementation of diet with Lyco and Toco provided antioxidant defense, with strong chemopreventive activity against DMBA-induced mammary tumors.

Two-stage PCR assay for detection of human brucellosis in endemic areas.

BackgroundBrucellosis is a common zoonosis that can cause a severe febrile illness in humans. It constitutes a persistent health problem in many developing countries around the world. It is one of the most frequently reported diseases in Saudi Arabia and incidence is particularly high in the Central region, and around the city of Riyadh. The aim of this study was to evaluate a two-stage PCR assay for detection of human brucellosis particularly in endemic areas.MethodsA total of 101 serum samples were collected from patients with acute febrile illness (AFI) of unknown cause from two different locations in the Western region of Saudi Arabia. The first location (Northern) is characterized by a nomadic rural population while the second (Central) is a modern urban city. All samples were subjected to DNA extraction and Brucella genus-specific PCR amplification using B4/B5 primers of the bcsp31 gene. Positive B4/B5 samples were subjected to multiplex species-specific Brucella PCR amplification.ResultsIn the Northern location, 81.9% of the AFI samples were confirmed Brucella positive, while all the samples collected from the Central region proved to be Brucella negative. Samples positive for Brucella were subjected to multiplex species-specific Brucella amplification. B. abortus was detected in 10% and B. melitensis in 8% of the samples, while the majority (82%) of samples showed both B. abortus and B. melitensis. As expected, B. suis was not detected in any of the samples.ConclusionsThis study concluded that a two-stage PCR assay could be useful as a rapid diagnostic tool to allow the consideration of brucellosis as a possible cause of AFI, particularly in non-urban locations. It also recommends the collection of epidemiological data for such patients to obtain further information that may help in rapid diagnosis.

Antioxidant status and hormonal profile reflected by experimental feeding of probiotics

Excessive production of free radicals can result in tissue damage, which mainly involves generation of hydroxyl radical and other oxidants. Such free radical-induced cell damage appears to play a major role in the pathogenesis of many diseases. Probiotics have been used therapeutically to modulate immunity, improve digestive processes, lower cholesterol, treat rheumatoid arthritis, and prevent cancer. The proposed research was designed to evaluate the changes in oxidative and antioxidative profile in addition to metabolic-related hormones of living animal model, which may generally affect the health status. Two groups of rabbits (10 animals each) were allocated in hygienic cages of controlled animal house. Control group received standard diet, and the other group received the same diet containing one probiotic for 30 days. Lactate dehydrogenase (LDH) activity in leukocytes, blood glucose, reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were estimated in different tissues. Malondialdehyde (MDA) and total proteins were also determined in different tissues. Certain hormones related to metabolism and growth were also evaluated. Leukocytic LDH activity was significantly increased along with nonsignificant increase of blood glucose in probiotics-fed animals. Results showed significant decreases in the levels of triiodothyronine and thyroid-stimulating hormone but showed significant elevations in thyroxine, insulin, growth hormone, and testosterone levels in animals fed with probiotics. Total proteins content was highly significantly elevated in liver, kidneys, and muscles of probiotic-administered animals. Microsomal GSH level was significantly decreased only in skeletal muscles of probiotic-treated animals. MDA was significantly lowered in animal tissues fed with probiotics. GSH-Px activity was elevated in hepatic and muscular microsomes of probiotic-supplemented animals while it was nonsignificantly increased in renal microsomes. Microsomal SOD activity was elevated in liver, kidneys, and skeletal muscles of probiotics-administrated animals. It is concluded that supplementation of probiotic may enhance antioxidant efficacy and scavenge free radicals and thus may be used as a preventive measure for protection against free radicals-induced disorders.

Serum free L-carnitine in association with myoglobin as a diagnostic marker of acute myocardial infarction

BACKGROUND Early diagnosis of acute myocardial infarction (AMI) in patients with chest pain is necessary to initiate appropriate treatment. Elevation of ST-segment in ECG is the only marker that cardiologists depend on in diagnosis. The aim of this study was to monitor the level of serum free L-carnitine in combination with myoglobin (Myo) and creatine kinase (total activity and CK-MB level) for usefulness as a predictor of AMI in ICU patients. DESIGN AND METHODS In the present study serum total CK activity and CK-MB, Myo, and free L-carnitine levels were determined in 90 patients admitted to the ICU at Ain Shams University Hospital and correlated the sensitivity and specificity of each parameter. RESULTS Obtained data revealed that, 47/90 who were diagnosed as AMI showed a highly significant reduction in serum free L-carnitine level in all cases as compared to normal control (P<0.001), 24/90 diagnosed as unstable angina showed a non significant reduction of serum carnitine and 19/90 who were diagnosed as noncardiac showed non significant changes in the level of serum free carnitine as compared to normal control. In addition, serum free L-carnitine level was negatively correlated to CK-MB and Myo (r=-0.61 and -0.52) respectively. The sensitivity of carnitine assay was considerably higher (95.5%) compared to CK-MB (87%) and Myo (89.5%) even considering patients with a short delay until admission. CONCLUSION Comparing the changes in serum total CK, levels of CK-MB, Myo and carnitine, the sensitivity and specificity were significantly higher for serum free L-carnitine. For this reason, serum free L-carnitine can be used as a good predictor for AMI diagnosis from other diseases.

Hypermethylation of P15, P16, and E-cadherin genes in ovarian cancer

Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells. Two groups of patients were selected: the first group suffered from epithelial serous ovarian tumors and the second group suffered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specific polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16). Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64.29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78.57% of ovarian cancer patients. Methylation of E-cadherin was significantly correlated with different stage of disease (p < 0.05). It was found that the risk of E-cadherin hypermethylation was 1.347-fold, while risk of p15 hypermethylation was 1.543-fold and p16 was 1.2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions. In conclusion, Dysfunction of the cell cycle and/or the cell–cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.

Hypolipidemic effect of fruit fibers in rats fed with high dietary fat

The hypolipidemic effect of 10% fruit fibers in rats fed with high-fat diet (HFD) was evaluated. This study was conducted on a total of 50 male Albino rats divided into 10 equal groups fed with different types of dietary fruits. The feeding period lasted for 24 weeks. Fasting blood samples were collected and sera separated and subjected to lipid profile assay and atherogenic index. In addition, total antioxidant activity of different fruits was determined. The results obtained showed that pomegranate had higher content of antioxidants followed by apple, strawberry and guava compared with other fruits. Rats fed with 20% coconut oil showed a highly significant elevation in the levels of serum total cholesterol, low-density lipoprotein cholesterol and atherogenic factor while the level of high-density lipoprotein cholesterol was significantly decreased when compared with control rats. Histological examination revealed that there was a large lipid and cholesterol deposition in the livers of rats fed with HFD. The potential in lowering the levels of plasma total cholesterol and triglyceride is in the following order: pomegranate > apple > strawberry > guava > papaya > mandarin and orange. Accumulation of hepatic lipid droplets was diminished when compared with the HFD group. Also, antiatherogenic is better than the untreated groups. Accordingly these hypolipidemic effects may be due to high-fiber content and antioxidant activity of these fruits.