Silibinin improves the cytotoxicity of methotrexate in chemo resistant human rhabdomyosarcoma cell lines

To investigate whether silibinin [SDH] could overcome chemoresistance of methotrexate [MTX]-resistant human rhabdomyosarcoma [hRD]. This study was conducted at the Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq from October 2012 to March 2013. In this in vitro study, resistance to MTX was induced in hRD cell line, the cells were treated with different concentrations of MTX or SDH alone, and in combination. Cell viability was determined by tetrazolium assay. The SDH in a concentration-dependent pattern, enhanced the sensitivity of MTX-resistant cells to the maximum cytotoxic concentration of MTX, and decreased the IC[50] [concentration resulting in 50% inhibition of cell growth] of MTX by 17.8 fold. The decrease in IC[50] of MTX was negatively correlated with increasing SDH concentrations with R[2] = 0.78 and p=0.04. The SDH improves the sensitivity of MTX-resistant hRD cell lines to the cytotoxic activity of MTX in concentration-dependent pattern

Anti-inflammatory activity of telmisartan in rat models of experimentally-induced chronic inflammation: comparative study with dexamethasone

Recently, significant progress has been made through the application of peroxisome proliferator activated receptor- [PPAR-] agonists as anti-inflammatory drugs that are efficacious, relatively free of side effects, and can be used effectively for a long time. The present study was designed to evaluate the dose-response relationship of the anti-inflammatory activity of telmisartan in rat models of chronic inflammation. The study protocol includes four stages: First stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of different doses of telmisartan in rat model of formaldehyde-induced chronic inflammation. Second stage: six rats were used to study the anti-inflammatory activity of telmisartan [1.5 mg/kg] in combination with dexamethasone [0.5 mg/kg] in the same model. Third stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of telmisartan in rat model of cotton pellet-induced granuloma. Fourth stage: six rats were used to study the anti-inflammatory activity of telmisartan [1.5 mg/kg] when used as adjuvant with dexamethasone [0.5 mg/kg] in the same model. Telmisartan in a dose-dependent pattern [0.1, 0.2. 0.4, 0.6, 1.5, 3 mg/kg] significantly suppressed inflammation in rat models of formaldehyde-induced chronic inflammation and cotton pellet-induced granuloma. When combined with dexamethasone, telmisartan [1.5 mg/kg body weight] significantly suppressed inflammation in both models, which is significantly higher than all of the effects produced by other approaches of treatment when telmisartan used alone. In conclusion, telmisartan decreased formaldehyde-induced chronic inflammation and cotton-pellet induced granuloma in rats in a dose-dependent pattern. Therefore, it may be considered as a potential treatment for chronic inflammatory conditions in human

Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piromcam and meloxicam

To evaluate the anti-inflammatory effect of Silymarin in patients with knee osteoarthritis OA in comparison with piroxicam and meloxicam. A double-blind clinical trial was performed at the Department of Rheumatology, Baghdad Teaching Hospital, Baghdad, Iraq during the period from October 2004 to September 2005, in which 220 patients 79 males and 141 females with painful knee osteoarthritis were randomized into 5 groups, treated with either silymarin 300mg/day, piroxicam 20mg/day, meloxicam 15mg, or a combination of silymarin with piroxicam or meloxicam. Serum levels of interleukin-1 alpha, interleukin-8, and the complement proteins C3 and C4 were assessed at zero time, and after 8 weeks. Silymarin reduces significantly serum levels of IL-1 alpha and IL-8, C3 and C4 after 8 weeks compared to the pre-treatment levels. Piroxicam showed no significant reduction in IL-1 alpha levels, while IL-8 decreased significantly, compared to pre-treatment value. Meloxicam elevates serum levels of IL-1 alpha significantly, while IL-8 did not significantly change compared to the pre-treatment value. Piroxicam or meloxicam produced slight, non-significant increase in serum levels of complement proteins after the 8-week treatment period. Adjunct use of silymarin with piroxicam results in significant reduction in both cytokines IL-1 alpha and IL-8, and serum levels of C3 and C4. However, its adjunct use with, meloxicam did not reveal any significant changes in this respect. Silymarin reduces the elevated levels of interleukins and complement proteins, when used alone, or in combination with NSAIDs for the treatment of knee OA

Effects of silibinin hemisuccinate on the intraocular pressure in normotensive rabbits

To evaluate the effects of silibinin hemisuccinate on the normal intraocular pressure [IOP] in rabbits. This study took place in the Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad during the period from January to June 2005. Twenty-five New Zealand white rabbits weighing 1.5-2.5 kg were used in this study. The effects ofcorneal instillation of various concentrations of silibinin hemisuccinate [0.5%, 0.75% and 1%] dissolved in arachis oil, on the normal intraocular pressure in rabbits were evaluated using indentation tonometry; in addition to the possible modulation of normal lOP-recovery time after intravenous infusion of 20% sodium chloride solution. The results showed that within 30 minutes of application, silibinin in various concentrations significantly reduces IOP in comparison to baseline values [P<0.05], with greater reduction being achieved with 0.75%. The effect of IOP reduction lasts 2-3 hours and proportionate to the concentration used. Moreover, remarkable delay in IOP recovery was observed after instillation of silibinin compared with the vehicle treated [arachis oil] animals, indicating interference with aqueous humor formation. The results obtained in this study provide experimental evidences for the effectiveness of silibinin in the reduction of IOP and possible modulation of its regulatory mechanisms

Protective effect of melatonin against chlorpromazine-induced liver disease in rats

To evaluate the possible protective effect of orally administered melatonin against Chlorpromazine [CPZ]-induced liver disease in rats. We performed this study in the College of Pharmacy, University of Baghdad during the period from May to October 2004. The hepatoprotective effect of melatonin was studied through treatment of rats with single dose [10 mg Kg-1] orally, 7 days before and during the period of CPZ treatment, and 7 days after the induction of suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde [MDA] and glutathione [GSH] in liver tissue homogenate, activities of the liver aminotransferases, alanine transaminase [ALT] and aspartate transaminase [AST] in serum, in addition to serum level of bilirubin [total and conjugated] were evaluated. Liver tissue sections were examined to follow histological changes. Analysis of data showed that treatment with melatonin significantly attenuated the oxidative stress parameters as evidenced by lowering MDA levels in tissue homogenate while not affecting GSH levels. Serum activities of ALT, AST and serum bilirubin were normalized with both pre-treatment and post-treatment with melatonin. Data revealed that post-treatments with both saline and melatonin restore hepatic activity; however, melatonin showed significant reduction in ALT activity and bilirubin level than saline post-treatment. Additionally, histological evaluation revealed improvement of liver damage in this respect. The presented data indicated that orally administered melatonin in pharmacological doses protects against CPZ-induced liver disease in rats

Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin

This project was designed to evaluate the effects of melatonin and zinc on the glycemic control in type 2 diabetes mellitus [T2DM] patients with inadequate response to the oral hypoglycemic agent metformin. A placebo controlled, double-blind clinical trial was performed at the Specialized Center for Endocrinology and Diabetes, Al-Rusafa Directorate of Health, Baghdad, Iraq during the period from February to July 2005, in which 46 type 2 diabetic patients were selected and allocated into 3 groups, these groups were treated with single daily oral doses of both 10 mg melatonin and 50 mg zinc acetate alone; 10 mg melatonin and 50 mg zinc acetate in addition to the regularly used metformin or placebo, given at bed time for 90 days. We measured the fasting plasma glucose [FPG], glycated hemoglobin [HbA1C] and serum C-peptide before starting the treatment [zero time] and after 30 and 90 days of treatment. We also performed post-prandial glucose excursion test [PPGE] for selected patients from the second and third groups before starting the treatment and after 90 days. Daily administration of melatonin and zinc improved the impaired fasting and post-prandial glycemic control and decreased the level of glycated hemoglobin; addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. The combination of melatonin and zinc acetate, when used alone or in combination with metformin improves fasting and post-prandial glycemic control in T2DM patients

dependent effects of isosorbide dinitrate on the antioxidant profile in blood cells of IHD patients

The beneficial effects of organic nitrates in ischemic heart diseases have been known since 1867, but it is only recently that it became fully recognized that they act by releasing nitric oxide in the vascular wall, perhaps substituting for a lack in endogenous nitrate. It is possible that nitric oxide radical [NO] in high concentrations can, at least theoretically, have adverse influences on the antioxidant profile of human blood cells [Erythrocytes and Leukocytes]. The effects of various doses of isosorbide dinitrate [ISDN] in inducing a stste of oxidative stress in blood cells which may be reflected in changes in the following parameters: [Cytosolic glutathione, lipid peroxidation, and antioxidant enzymes activities] were examined, and it is found that, a dose dependent increase in lipid peroxidation and a depletion of cytosolic glutathione was occurred, with subsequent alterathions in the activities of the antioxidant enzymes [glutathione-S- transferase [GST], glutathione reductase [GSR], glutathione peroxidase [GSH-Px], Superoxide dismutase [SOD] and Catalase [CAT]]. These results reflect worsening effects of the state of oxidative stress previously induced by ischemic changes in the myocardium.

Glutathione and its metabolizing enzymes in chronic renal failure patients pre and post dialysis

Uremic toxin retained in the blood of chronic renal failure patients could affect the glutathione defense system against peroxides. Twenty uremic patients who are maintained on regular hemodialysis are selected and twenty four reference subjects saved as a control. The following parameters are measured in whole blood and erythrocyte pre and post-dialysis: glutathione levels [GSH], glutathione Stransferase [GST] glutathione reeductase [GSR], total and selenium glutathione peroxidase [GSH-PX] and lipid peroxidation [MDA]. The results showed severe depletion of glutathione, inhibition of GSH-Px and GSR, rise in GST and MDA contents. Dialysis could not completely revert these changes. Therefore uremia may impair the defense mechanism against free radical mediated injury