THE POSSIBLE CARDIOPROTECTIVE EFFECTS OF DIFFERENT FRACTIONS OF ARTICHOKE EXTRACTS AGAINST 5-FU INDUCED CARDIOTOXICITY IN ALBINO RATS

Objective: The present study aimed to evaluate the cardioprotective effects of ethyl acetate and methanolartichoke extracts(Cynara scolymus L.) against 5-Flurouracil (5-FU) induced cardiotoxicity in rats.Methods: Thirty-six albino rats were divided randomly and equallyin to six groups (each group with 6 rats): I, negative control, received (2 ml/kg/d)of dimethyl sulfoxide (DMSO) orally for 30 successive d; II, positive control, received (2 ml/kg/d) of (DMSO) orally for 30 successive d, and subsequently administered a single dose of 5-FU (150 mg/kg) by intraperitoneal injection on 27thd in assossiation with DSMO; III and V, received (200 mg/kg/d) of oral methanol and ethyl acetate artichoke extracts respectivelyfor 30 successive d; V and VI, received(200 mg/kg/d) of oral methanol and ethyl acetate artichoke extracts respectively for 30 successive d,with a subsequently received single dose of 5-FU (150 mg/kg) by intraperitoneal injection on 27th d of the experiment.Results: Prophylactic treatment of ethyl acetate and methanol artichoke extracts significantly attenuates the increased level of serum cardiac troponin T (CTn-T) and tumor necrosis factor-a(TNF-a)caused by 5-FU-induced cardiotoxicity in experimental albino rats while it increases the serum level of total antioxidant capacity (T-AOC).Conclusion: Results of the present study suggest that methanol and ethyl acetate artichoke extracts may be an effective modulator in mitigating 5-FU induced cardiotoxicity.Â

Effects of Different Concentrations of Melatonin on the Time-course of Nitrite–induced Oxidation of Hemoglobin: In vitro Study

         Melatonin is a potent scavenger of reactive oxygen species or free radicals like superoxide and hydroxyl radicals. The oxidation of hemoglobin to methemoglobin (meth-Hb) by oxidizing compounds has been widely studied. The present work was designed to evaluate the ability of different concentrations of melatonin to inhibit nitrite–induced oxidation of hemoglobin. Blood samples were obtained from apparently healthy individuals from which erythrocyte hemolysate was prepared. Different concentrations of melatonin (10-9-1.0 mg/ml) were incubated for 10 min with the hemolysate, then to the resultant mixture 1 ml of sodium nitrite (final concentration 0.6 mM) was added, and the formation of meth-Hb was measured by monitoring absorbance of light at 631 nm each min for 30 min. Control samples without melatonin were utilized for comparison. Nitrite caused rapid oxidation of hemoglobin to meth-Hb in control samples; in the presence of melatonin, the oxidation process was delayed in a dose–dependent manner. The effect of melatonin on the time course of nitrite-induced oxidation of Hb showed that melatonin has a protective effect initiated early after addition along with nitrite. Melatonin also affect the time required for the formation of meth-Hb, the   time required to convert 50% of the available Hb to meth-Hb was 4 min in the absence of melatonin, and became  17, 22, 26, 30, 114 and 383  min with increasing melatonin concentrations (10-9, 10-6, 0.001, 0.01, 0.1, and 1.0 mg/ml  respectively). In conclusion, melatonin in a concentration  and time dependent manner can protect Hb from oxidation by nitrite; melatonin delays the onset of autocatalytic stage and the protective effect extended over long period of time. Key words: melatonin, erythrocytes oxidatio

The Possible Cardio-Protective Effects of Ethanolic Artichoke Extract against 5- Fluorouracil Induced Cardiac Toxicity in Rats

Cardiac toxicity can occur during the therapy with several cytotoxic drugs, including 5- Fluorouracil (5- FU). It is an antimetabolite that acts during the S phase of the cell cycle and is activated by thymidine phosphorylase into fluorodeoxyuridylate (5 fluoro 2'deoxyuridine 5'monophosphate, 5-FdUMP) that inhibits thymidylate synthase, thus preventing DNA synthesis that leads to imbalanced cell growth and ultimately cell death. It is still a widely used anticancer drug, since 1957. The present study aimed to evaluate the possible cardio-protective effects of ethanolic artichoke extract (Cynara scolymus L.) against 5-fluorouracil (5-FU) induced cardio-toxicity in rats by evaluating serum levels of Alanine aminotransferase, aspartate aminotransferase and creatine kinase enzymes. Methods: Twenty -four female albino rats were randomly divided into 4 groups each group with 6 rats. Group I: (negative control) received oral daily dose of dimethyl sulfoxide (DMSO) (2 ml/kg /day) for 10 successive days. Group II: (positive control) received oral daily dose of DMSO (2 ml/kg /day) for 10 successive days and subsequently administered single dose of 5-FU (150 mg/kg) by intraperitoneal injection on 8th day in association with DMSO. Groups III: received oral daily dose of ethanolic artichoke extract (200 mg/kg/day) for 10 successive days. Groups IV: received oral daily dose of ethanolic artichoke extract (200 mg/kg/day) for 10 successive days with subsequently administered single intraperitoneal dose of 5-FU (150 mg/kg) on 8th day in association with ethanolic extract. Results: Treatment of ethanolic artichoke extract prior 5-FU intoxication significantly attenuate the increase of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine kinase (CK) enzymes activities caused by 5-FU-induced cardio-toxicity in rats. Conclusions: Results of the present finding suggest that the ethanolic artichoke extract may be an effective modulator in mitigating 5-FU induced cardiac toxicity in rats. Keywords: Ethanolic artichoke extract, 5-Fluorouracil, Cardio-protection, AST, ALT and CK

Therapeutic Use of Silymarin in the Management of Suspected Renal and Hepatic Injury Produced by NSAIDs in Osteoarthritis Patients

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) mostly associated with renal and hepatic adverse effects, and the adjunct use of compounds with potent protective effects, like silymarin, may be one of the choices to avoid these effects. This project was designed to evaluate the protective effect of silymarin against the suspected renal and hepatic injury induced with long term use of NSAIDs; 220 patients with osteoarthritis were randomized into 5 groups and treated with either silymarin 300mg/day alone, piroxicam 20mg/day alone, meloxicam 15mg/day alone or the combination of each of them with silymarin for 8 weeks. The renal and hepatic functions were evaluated before starting treatment and after 8 weeks including assessment of serum levels of urea, creatinine and the activities of the hepatic enzymes alkaline phosphatase (ALP), glutamic-oxalic acid transaminase (GOT) and glutamic-pyruvic acid transaminase (GPT). The results indicated that using NSAIDs alone produced elevation in the markers of renal and hepatic damage that can be successfully prevented or reversed when silymarin adjunctly used with them. In conclusion, silymarin when co-administered with the NSAIDs (piroxicam or meloxicam) decreases their renal and hepatic toxicities in OA patients. Key words: Silymarin; Piroxicam, Meloxicam; Nephroprotection; Hepatoprotection 

Dose-dependent Anti-inflammatory Effect of Silymarin in Experimental Animal Model of Acute Inflammation

Silymarin, a flavolignans from seeds of ‘milk thistle’ “Silybum marianum†has been widely used from ancient times because of its excellent hepatoprotective action. It has been used clinically to treat liver disorders including acute and chronic viral hepatitis, toxin/drug-induced hepatitis and cirrhosis and alcoholic liver disease. The efficacy and dose-response effect of silymarin (125, 250 and 500 mg/kg) were assessed using egg albumin-induced paw edema in rats as a model of acute inflammation. In this model, 56 rats were used and allocated into 7 subgroups each containing 8 rats. All treatments were given intraperitonealy 30 minutes before induction of inflammation by egg albumin and then the increase in paw edema was measured 1h, 2h and 3h after induction of inflammation by using the vernier caliper. The results indicated that silymarin, at doses range used, significantly lowered paw edema (P<0.05) an effect comparable to that produced by the reference drugs, acetyl salicylic acid, meloxicam and dexamethazone. Paw edema suppressive effect of silymarin 250 and 500 mg/kg was comparable and both of them were significantly different from that of silymarin 125 mg/kg (P<0.05). Therefore, silymarin exert an important anti-inflammatory activity in animal model of acute inflammation, which was significantly increased as the dose increased up to 250 mg/kg. Key words: Silymarin, acute inflammation, dose-respons

The Efficacy of Topically Applied Silymarin in the Treatment of Herpes Labialis Ulcers

Herpes labialis is an infection caused by the herpes simplex virus, characterized by an eruption of small and usually painful blisters on the skin of the lips, mouth, gums, or the skin around the mouth. Although there is no successful treatment available, the local use of compounds with effective anti-inflammatory and cytoprotective effects may be of value in this respect. This project was designed to evaluate clinically the local use of silymarin, a group of flavonoids with powerful antioxidant, anti-inflammatory and cytoprotective activity, in the treatment of herpes simplex ulcer. Fifty three patients with herpes labialis ulcers (HLU) were enrolled in this randomized, single blinded, placebo controlled clinical study, and they were allocated into 4 groups, treated with 1%, 3% and 5% silymarin paste and placebo formula respectively. Patient's responses to treatment were followed by clinical evaluation of healing time, size of the ulcers and pain sensation, in addition to evaluating biochemical and immunological markers of the oxidative stress and inflammatory response. HLU patients showed dose dependent improvement in the healing time, pain score and size of ulcer as a result of treatment with various concentrations (1%, 3% and 5%) of silymarin paste, associated with improvement in the oxidative stress state and immunological parameters. In conclusion, silymarin can be used locally as paste formula for the treatment of HLU, an effect which may be attributed to its antioxidant, anti-inflammatory and cytoprotective properties. Keywords: Herpes labialis, ulcers, silymari

Changes in Serum Levels of Tumor Necrosis Factor-Alpha and Antioxidant status in Different Stages of Malignant Prostate Cancer Patients in Iraq

Chronic inflammation can induce proliferative events and posttranslational DNA modifications in prostate tissue through oxidative stress. The present study was designed to evaluate the changes in serum levels of TNF-α, malomdialdehyde (MDA) and total antioxidant status (TAS) patients with different stages of malignant prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). One hundred males (age range of 58-72 years) with different stages of malignant PCa were recruited from the Radiotherapy and Nuclear Medicine Teaching Hospital in Baghdad during the period from September 2010 to April 2011. The patients were categorized according to the 4 disease stages (I, II, III, and IV); 25 patients with benign prostatic hyperplasia (BPH) and 25 normal healthy subjects were considered as comparator groups. Blood samples were taken from all subjects for analysis of TNF-α TAS and MDA levels. The results showed significant differences between the four stages of PCa patients in all parameters; however, highly significant difference was observed in stage IV compared to control and BPH patients. In conclusion, TNF-α and total antioxidant status could be utilized for marking the advanced stages of malignant PCa.    Key words: Malignant Prostate cancer, Inflammation, TNF-α, Oxidative stres