Mostafa Kamal Hassan

Erectile dysfunction drugs and oxidative stress in the liver of male rats

Erectile dysfunction (ED) affected the lives of more than 300 million men worldwide. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by antioxidant enzymes. Therefore, the present study aims at investigating the changes in the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione reductase as well as protein expression of glutathione peroxidase and glutathione S-transferase after treatment of male rats with a daily dose of sildenafil (1.48 mg/kg), tadalafil (0.285 mg/kg) and vardenafil (0.285 mg/kg) for three weeks. In addition, levels of reduced glutathione and malondialdyhyde (MDA) were assayed. The present study showed that sildenafil, vardenafil, and tadalafil treatments significantly decreased the levels of glutathione, MDA and the activity of glutathione reductase. In addition, vardenafil and sildenafil increased the activity of superoxide dismutase and catalase. Interestingly, western immunoblotting data showed that vardenafil induced the activity of glutathione peroxidase (GPX) and its protein expression, whereas tadalafil and sildenafil inhibited such enzyme activity and its protein expression. In addition, the protein expression of GST π isozyme was markedly reduced after treatment of rats with sildenafil. It is concluded that ED drugs induced the activities of both SOD and catalase which consequently decreased MDA level. Therefore, decrement in MDA levels could increase nitric oxide–cGMP level which in turn promotes the erection mechanism.

Managerial Innovations in the Egyptian Public Health Sector: An Empirical Investigation

The purpose of this article is to analyze the process of restructuring the Egyptian public health sector according to the new mode of governance principles and the concomitant dilemmas in the process. Based on an interpretative methodology, the findings of this research indicate that (a) despite some positive changes, serious doubts remain over the commercialization of basic public services; (b) confusions have emerged regarding the identity of public hospitals; (c) despite the introduction of the business management principles, the centralized hierarchical power of the state over the local governmental hospitals remains intact; (d) the new system has degraded the professional standards of medical practitioners and made them subservient to the whims of the financial management professionals; and (e) there have been some negative effects on equity.

Corporate governance disclosure and share price accuracy

Purpose – The purpose of this paper is to investigate the impact of corporate governance disclosure on share price accuracy of listed companies in the United Arab Emirates (UAE). Design/methodology/approach – Data on corporate governance disclosure were obtained from the financial statements of companies listed in the UAE stock market, and share price accuracy indices were crafted from each company’s weekly share price returns between 2008 and 2009, using generalized least squares regression analysis. Multiple regression analysis with fixed effects was then implemented to test the study hypotheses. Findings – Voluntary corporate governance disclosure has a significant positive impact on share price accuracy. There is also evidence that mandatory corporate governance disclosure plays an important positive role on share price accuracy in the UAE business environment. Research limitations/implications – This paper covers a two-year transitional period during implementation of a new corporate governance code ...

Effects of benzo[a]pyrene as an environmental pollutant and two natural antioxidants on biomarkers of reproductive dysfunction in male rats.

Benzo[a]pyrene (B[a]P) is an environmental toxicant and endocrine disruptor. Therefore, the aim of the present study was to investigate the toxicity of B[a]P in testis of rats and also to study the role of silymarin and thymoquinone (TQ) as natural antioxidants in the alleviation of such toxicity. Data of the present study showed that levels of testosterone, estrogen and progesterone were significantly decreased after treatment of rats with B[a]P. In addition, B[a]P caused downregulation of the expressions of steroidogenic enzymes including CYP17A1 and CP19A1, and decreased the activity of 17-β hydroxysteroid dehydrogenase (17β-HSD). Moreover, B[a]P decreased the activities of antioxidant enzymes including catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD), and significantly increased free radicals levels in testis of male rats. However, pretreatment of rats with silymarin prior to administration of B[a]P was found to restore the level of free radicals, antioxidant status, and activities of steroidogenic enzymes to their normal levels in testicular tissues. Moreover, histopathological finding showed that silymarin recovered the abnormalities occurred in tubules caused by B[a] P in testis of rats. On the other hand, TQ showed pro-oxidant effects and did not ameliorate the toxic effects of B[a] P on the testicular tissue since it decreased antioxidant enzymes activities and inhibited the protein expression of CYP11A1 and CYP21A2 compared to control rats. Moreover, TQ decreased the levels of testosterone, estrogen, and progesterone either in the presence or absence of B[a]P. It is concluded that B[a]P decreased testosterone levels, inhibited antioxidant enzymes activities, caused downregulation of CYP isozymes involved in steroidogenesis, and increased free radical levels in testis. Moreover, silymarin was more effective than TQ in restoring organism health and alleviating the deleterious effects caused by B[a]P in the testis of rats. Due to its negative impact, it is highly recommended to limit the use of TQ as a dietary supplement since millions of people in the Middle East are using it to improve their health.

Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats.

Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along with its corresponding enzyme marker ECOD activity. It is concluded that changes in the expression and activity of phase I drug-metabolising enzymes could change the normal metabolic pathways and might enhance the deleterious effects of exogenous as well as endogenous compounds.

Schistosoma mansoni Changes the Activity of Phase II Drug-Metabolizing Enzymes: Role of Praziquantel as Antibilharzial Drug

Schistosomiasis is one of the major health problems in many developing countries and causes liver damage. In addition, under the influence of schistosomiasis most of the endogenous toxic compounds can be conjugated with glutathione via glutathione S-transferase. Therefore, the present study showed the effect of Schistosoma mansoni after 20, 30, 45, 60, and 75 days post-infection on the activity of glutathione-S-transferase (GST) and glutathione reductase (GR), and on the levels of glutathione [GSH] in the livers of male mice. In addition, anti-schistosomal drug (praziquantel) was administered orally [60 mg/kg body weight] for three consecutive days before decapitation of the infected mice at each time point. In the present, depletion of GSH levels was observed at 45, 60 and 75 days post-infection. However, treatment of infected mice at 45, 60, and 75 days post-infection with praziquantel for three consecutive days before decapitation at each time point restored the increased GSH levels to their normal values compared with control groups. Inhibition of GST and induction of GR activities in the livers of S. mansoni-infected mice at all time-points were restored to their normal levels after praziquantel treatment. It is concluded that S. mansoni infection changed the activities of GST, GR and GSH levels. Moreover, it has been found that praziquantel treatment of S. mansoni-infected mice restored such alterations to their normal values and this recovery could alleviate the deleterious effects of S. mansoni infection. In addition, the present study could provide new evidence to the damage occurred in livers of S. mansoni-infected hosts. Also, it is suggested that praziquantel is the best drug of choice for schistosoma mansoni treatment.