Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a common reactive oxygen intermediate generated by various forms of oxidative stress. Aim: The aim of this study was to investigate the DNA damage capacity of H<sub>2</sub>O<sub>2</sub> in HepG2 cells. Methods: Cells were treated with H<sub>2</sub>O<sub>2</sub> at concentrations of 25 mM or 50 mM for 5 min, 30 min, 40 min, 1 h, or 24 h in parallel. The extent of DNA damage was assessed by the comet assay. Results: Compared to the control, DNA damage by 25 and 50 mM H<sub>2</sub>O<sub>2</sub> increased significantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions: Our findings confirm that H<sub>2</sub>O<sub>2</sub> is a typical DNA damage-inducing agent and thus is a good model system to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantly with H<sub>2</sub>O<sub>2</sub> concentration and time of incubation but later decreased likely due to DNA repair mechanisms and antioxidant enzymes.Keywords: DNA damage; hydrogen peroxide; HepG2 cells; comet assa

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist). Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments.In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors

Acute respiratory viral infections aggravate arterial endothelial dysfunction in children with type 1 diabetes mellitus.

Despite improvements in therapy for children with type 1 diabetes, the prevalence of cardiovascular morbidity in adulthood due to accelerated atherosclerosis remains significant (1). Similar to other cardiovascular risk factors, the diabetic state facilitates arterial endothelial injury, a primary event in the pathogenesis of atherosclerosis (2). Although several pediatric studies have reported an association of diabetes with arterial endothelial dysfunction (3,4), pathogenic animal studies have suggested that even though this disease predisposes to endothelial dysfunction and atherosclerosis, it might not be sufficient to cause them (5). Notably, type 1 diabetes increases the propensity for both chronic and acute infections in part by weakening the immune mechanisms (6). The risk is particularly increased for respiratory tract infections, but other infections have also been associated with diabetes (7). Furthermore, diabetic patients are at greater risk for infection-related mortality (8), and the excess risk appears to be linked to cardiovascular diseases (9). In the present study, we investigated whether viral respiratory tract infections in children with type 1 diabetes might impose an additional burden on the arterial endothelial function

Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking

Barira Islam,1,* Charu Sharma,2,* Abdu Adem,3 Elhadi Aburawi,1 Shreesh Ojha3 1Department of Paediatrics, 2Department of Internal Medicine, 3Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates *These authors contributed equally to this work Abstract: Statins are hypolipidemic drugs that are effective in the treatment of hypercholesterolemia by attenuating cholesterol synthesis in the liver via competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Recently, dietary changes associated with drug therapy have garnered attention as novel drugs to mitigate or ameliorate hypercholesterolemia. The present study was undertaken to observe different dietary polyphenols that can bind to the active site of HMGR and inhibit it. Results from the 12 dietary polyphenols tested reveal that polyphenols can bind to HMGR and block the binding of nicotinamide adenine dinucleotide phosphate (NADP+). We observed that the rigidity of phenolic rings prevents the polyphenols from docking to the enzyme activity site. The presence of an ester linkage between the phenolic rings in (–)-epigallocatechin-3-gallate (EGCG) and the alkyl chain in curcumin allows them to orient in the active site of the HMGR and bind to the catalytic residues. EGCG and curcumin showed binding to the active site residues with a low GRID score, which may be a potential inhibitor of HMGR. Kaempferol showed binding to HMG-CoA, but with low binding affinity. These observations provide a rationale for the consistent hypolipidemic effect of EGCG and curcumin, which has been previously reported in several epidemiological and animal studies. Therefore, this study substantiates the mechanism of polyphenols on the activity of HMGR by molecular docking and provides the impetus for drug design involving further structure–function relationship studies. Keywords: polyphenols, HMG-CoA, EGCG, curcumin, docking, in silic

Experimental study comparing burn healing effects of raw South African Shea butter and the samples from a Libyan market

Background: The fat extracted from the nut of the African Shea tree (Vitellaria paradoxa) is called Shea butter. It has multiple uses at the local level as it is used in cosmetic products and as a cocoa butter substitute in chocolate industries. It has a high nutritious value and is also a valuable product on the local, national, and international markets, making it the ideal candidate to research and invest in. Aim: This study is a comparative experimental study of the possible burn healing effects between imported South African raw Shea butter and samples in a Libyan market. Method: The control samples were brought from South Africa (Benin traditional markets). A total of 18 different samples were collected from different sale centers in Tripoli, including pharmacies, beauty shops, and spices shops, in addition to one sample brought from Poland. Animal experiment on burn healing effect was carried out on nine male Sprague Dawley (350–400 g) rats aged 6–8 weeks old. After shaving the animal’s dorsum hair, a metal cube was used to create a deep second degree burn wound, and the cube was heated to 100°C for 20 seconds. Medication with Shea butter (control, T1, and T2) was initiated daily for one for these groups by the application of a thin film of the Shea butter samples on the burned areas. On days 1, 3, and 7, the rats were anesthetised and a sample from the burned scar tissue and skin adjacent were evaluated using pathological parameters. Results: The histological study indicates that the use of Shea butter T1 as topical treatment induces an immune response, which enhances the form of the presence of a large number of inflammatory cells in the epidermis and dermis layers. The treatment of burned skin with T2 lasted for 72 hours and it showed slightly significant healing in the normal structure of proliferative granulation tissue with accumulation of fibroblasts and inflammatory cells surrounding the sebaceous glands and hair follicles. Small areas of the epidermis which formed few layers were observed and some hair roots were grown. This was well seen in cases of T1 and T2. Shea butter bought as raw might have a bad effect on burned skin. Conclusion: Shea butter bought as raw might have bad effect on burned skin. On the other hand, the sample from Poland had a therapeutic effect, which was because of the additives such as avocado oil, grape seed oil, and others