Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. Several studies have already confirmed that the oxidative stress plays a major role in the pathogenesis of MTX-induced damage in the various organs. This study was carried out to determine whether garlic extract has a protective effect against MTX-induced hepatotoxicity and nephrotoxicity.
Thirty six rats were divided randomly into 6 groups: Group I (control): treated with normal salin. Group II: GE (500 mg/kg once for 16 days). Group III (MTX): was received double-dose MTX (20 mg/kg i.p, 7th and 14th day).Group IV: MTX +GE (20 mg/kg i.p, 7th and 14th day+ 100 mg/kg once for 16 days). Group V: MTX +GE (20 mg/kg i.p, 7th and 14th day+250 mg/kg once for 16 days). Group VI: MTX + GE (20 mg/kg i.p, 7th and 14th day+500 mg/kg once for 16 days). At the end of the experiment blood samples were collected to investigate serum levels of ALT, AST, ALP, Albumin, total bilirubin BUN and creatinine(Cr) In addition liver and renal was removed for measurement of MDA, TAC and GSH level and catalase (CAT), GPx, SOD activities and histopatological studies. Resalt show that serum ALT, AST, ALP, Albumin and liver renal tissue SOD, GPx, CAT and GSH were significantly decreased in group III, compare with control group.These parameters in group IV, V and VI increased compare with group III(p>0.001). Serum bilirubin, BUN and Cr and hepatic and renal MDA, significantly increased in group III, compare with control group(p>0.001) and decreased in group IV, V, VI compare With group III. Additionally, histopathological examinations revealed markedly ameliorated MTX-induced toxicity liver and renal structure.Our finding proved that garlic administration could have a protective role in MTX- induced hepatotoxicity and nephrotoxicity with could be due to its antioxidant properties.

BACKGROUND AND OBJECTIVE:
Methotrexate as a chemotherapy drug causes chronic liver damage and oxidative stress. The aim of this study was to evaluate the protective effect of hydroalcoholic extract of Cichorium intybus (CIE) on methotrexate (MTX) -induced oxidative stress.
METHODS:
In this experimental study, thirty Wistar male rats weighting 200-250 g were randomly divided into 5 groups (n = 6 in each group). Negative control group (normal saline 5ml/kg), positive control group reseaved normal salin orally for 11 days, and a single dose of MTX (MTX, 20mg/kg, i.p.) was administrated on the 7th day. Groups 3-5 received respectively 100, 200 and 400 mg/kg of CIE orally for 11 days, and a single dose of MTX was injected on the 7th day. 24 h after the last injection, animals were sacrificed. Blood samples were collected to determine serum biochemical parameters and livers were removed for biochemistry and histology investigation.
FINDINGS:
The result obtained from current study was showed a significant decrease in the levels of AST, ALT, ALP, GSH, CAT, SOD, GPx and significant increase in the levels of TB and MDA by MTX administration. Pre-treatment with CIE showed increase in the levels of AST, ALT, ALP, GSH, CAT, SOD, GPx and significant decrease in the levels of TB and MDA in all doses but the most significant alteration was observed in doses of 400 mg/kg (P<0.05). Histological results showed that methotrexate could lead to liver damage. also the hepatoprotective effect of the CIE was confirmed by the histological examination of the liver.
CONCLUSION:
The results revealed that CIE has protective effect on liver tissue damages induced by methotrexate. This effect of Cichorium intybus can be attributed to active ingredients of the plant with antioxidant properties.
 

First Name:elham Last name: Rostami
Title: Investigation of association between MDM2 single nucleotide polymorphism (SNP) 309 and Leukemia Risk in Khuzestan province
Supervisors:Dr.M.Mohamadi
Advisors:Dr.Sh.Bagheri
Degree:M.Sc Major: Biology Field: biochemistry
University:Shahid Chamran University of Ahvaz
Key Words:: MDM2 - polymorphism - Leukemia
Abstract : Leukemia is a progressive and malignant disease of hematopoietic members of the body which is created by abnormal proliferation and maturation of white blood cells and their precursors in the blood and bone marrow. Leukemia usually begins in the white blood cells and disrupt proliferation process of hematopoiesis and the body's natural immunity. Leukemia is the fifth most common cancer in the world.
Cells have different mechanisms by using different proteins against cancer. P53 is a tumor suppressor protein, that its activity is reduced in most cancers due to mutations in its gene or deviations in the expression of P53 pathway genes like MDM2. MDM2 is a oncogene, that encode a phosphoprotein which prevents the p53 activity by ubiquitin ligase activity.
Study on polymorphism at position 309 of Mdm2 gene have been done in various populations. In this study, this polymorphism wase investigated in khuzestan province leukemia by using of PCR-RFLP method. For this purpose this polymorphism was evaluated in 206 patients with leukemia (including 115 ALL and 91 AML) and 115 control samples. Based on the results position 309 of MDM2 polymorphism is associated with the risk of ALL (P-value:0.001 , X2= 69.45) and AML (P-value:0.001 , X2 = 46.02) in Khuzestan

 

After cardiovascular diseases and accidents, cancer is the third cause of death in Iran, and the second cause of death in developed countries. Leukemia is the fifth most common cancer in the world and include about 8 percent of total Neoplasms. Reports indicate that leukemia has increased in Iran. Cells have different mechanisms by using different proteins against cancer. p53 is a tumor suppressor protein and known as guardian of the genome.p21 is One of the p53 transcription target gene in response to cancer. This proteins can protect cells from cancer. deficiency in the activity of these two proteins could be One of the causes of cancer, polymorphism can change structure and functions of this proteins. polymorphism at codon 72 of p53 gene and codon 31 of p21 gene are frecuently studies in different populations. At this study, this polymorphism were investigated in khoozestan province leukemia by using of RFLP method. For this purpose two polymorphisms were evaluated in 206 patients with leukemia (including 115 ALL and 91 AML) and 115 control samples. For further investigation genotypes and alleles between the control group and each group of patients were conducted. Based on the results p53 codon 72 polymorphism is associated with the risk of leukemia in Khoozestan, While p21 codon 31 polymorphism did not show relation with leukemia in this population.

 
Methotrexate (MTX), as a chemotrapy drug is used widely to treat varius malignancy and outoimmune disease. According to previous studies, MTX causes liver damage and oxidative stress. Tragopogon extract contain flavonoid compound with antioxidant property. The aim of this study was to investigate the protective effect of Tragopogon Kemulariae extract (TKE), against Methotrexate (MTX)-induced liver and hemato toxicity in rats. Thirty wistar male rats were divided into 5 groups. Group I (control): treated with normal salin. Group II (MTX): was received double-dose MTX (20mg⁄kgi.p, 7th and 14th day).Group III: MTX + TKE (20mg⁄kgi.p, 7th and 14th day+100mg/kg/day). Group IV: MTX + TKE (20mg⁄kgi.p, 7th and 14th day+250mg/kg/day). Group V: MTX + TKE (20mg⁄kgi.p, 7th and 14th day+500mg/kg/day). After 17 days ALT, AST, ALP and serum levels of Albumin and total bilirubin were elevated in serum.CBC test for analyse platelet, WBC and hemoglobin was performed. In addition liver was removed for measurement of MDA, TAC and GSH level and catalase, GPX, SOD activities and histopatological studies. Resalt show that seram ALT, AST, ALP, Albumin PLT,WBC and liver SOD, GPX, CAT and GSH were significantly decreased in groupII, compare with control group. These parameters in group III, IV and V increased compare with group II. Serum bilirubin, and hepatic MDA, Significantly increased in group II, Compare with control group and decreased in group III, IV,V, compare. With group II. Our finding prov that TKE administration could have a protective role in MTX- induced liver and hemato toxicity wich could be due to its antioxidant properties.