Chemotherapeutic effect of Ulmus pumila leaves methanolic extract against N-methyl-N-nitrosourea-induced mammary carcinoma in female rats: An in vitro and in vivo study

Searching for a chemopreventive agent is an important approach for breast cancer management. The aim of the study was to evaluate the chemopreventive potential of Ulmus pumila (UP) leaves extract on breast tumorigenesis induced in experimental animals by N-methyl-N-nitrosourea. This target was undertaken through preparing several extracts from the fresh leaves of UP using different solvents against the breast adenocarcinoma cell line (MCF-7). Our in vitro results demonstrated that the methanolic extract of UP (UPME) showed the highest cytotoxic activity against the growth of MCF-7 cells. After determination of UPME safe dose (1/10) of a lethal dose, the in vivo results revealed that UPME treatment significantly decreased the activities of liver enzymes, kidney function, cancer antigen 15-3 (CA 15-3) level, urokinase plasminogen activator, heparanase, basic fibroblast growth factor, B-cell leukemia lymphoma 2, and cyclooxygenase-2. By contrast, total antioxidant capacity (TAC) was increased in therapeutic, protective, and prophylactic groups as compared to the tumor group. These improvements were supported with histopathological changes. These results indicated that the chemotherapeutic potential of UPME through stimulation of apoptosis and the suppression of angiogenesis, proliferation, and metastasis.

Induction of pancreatic thiol proteins by zinc protect against diabetogenic, oxidative and histological changes produced by arsenic toxicity in rats

Recent studies reported that, chronic arsenic exposure is always associated with an increase in the prevalence of diabetes mellitus. It is recognized that arsenic contributes to oxidative stress in several organs and systems including the islets of Langerhans through generation of reactive oxygen species [ROS]. So the current study was undertaken to elucidate the possible role of zinc as an antioxidant in the protection against diabetes mellitus induced by arsenic. Male Sprague-Dawley rats were given sodium arsenite daily at a dose of 1.5 mg/kg by gavage for 60 consecutive days. Another group of rats were injected I.P with zinc chloride 20 mg/kg for 2 days with one day interval, then was given sodium arsenite at a dose of 1.5 mg/kg by gavage every day for 60 consecutive days. Blood samples and pancreatic tissue specimens were collected from all the tested groups at the end of the experiment for biochemical evaluation and histological examination. The level of both thiobarbituric acid reactive substances [TBARs] and nitric oxide [NO] were significantly elevated in arsenite treated group as compared to control group. Hyperglycemia, hyper-insulinemia and low insulin sensitivity was observed. The activity of pancreatic thioredoxin reductase [TrxR] was lower than control group. Also, the levels of metallothionein [MT] and total glutathione [GSH] in pancreas increased significantly relative to the control group indicating the presence of stress and oxidative damage, respectively. Histological sections of pancreas of arsenic treated rats showed that a large number of islets were shrunken with low number of islet cells .The number of beta-cells decreased relative to the total islet cell number compared to control. Pre-treatment with zinc chloride before arsenic administration reversed the previous biochemical parameters and histological changes. The pancreatic TBARs and NO are reduced compared with arsenite treated group. Significant decrease in glucose level and decrease the level of insulin with increase insulin sensitivity was observed. Also pre-treatment with zinc resulted significant increase in the activity of TrxR, levels of MT and GSH. Zinc chloride prevented the reduction in beta-cell and islet cell number. Also it could restore the normal morphology of the islets. The current results clearly indicate the beneficial effects of zinc chloride in both controlling hyperglycemia and the protection of the pancreatic islet cells against oxidative stress in diabetes through induction of thiol proteins which may help setting a new direction toward the development of effective treatment of diabetes mellitus

IgA/transferrin ratio for the early prediction of latent liver cirrhosis

The B.C of our study was to assess the level of IgA and transferrin of patients with liver cirrhosis to determine the relation between liver cirrhosis and IgA/transferrin ratio. The study involved 32 subjects classified into patients without liver cirrhosis [n=12], and patients with liver cirrhosis [n=10] as well as a group of normal healthy subjects [n=10] for comparison. In all of these subjects, serum alanine [ALT] and aspartate [AST] aminotransferase activity as well as serum IgA and transferrin level were determined. Our results revealed that the mean values of both ALT and AST activities were significantly high in both groups of patients without liver cirrhosis and with liver cirrhosis [P<0.05], although the activity of both enzymes was relatively higher in patients with liver cirrhosis than in those without liver cirrhosis. Furthermore, the amount of IgA immunoglobulin showed very highly significant decreased values in patients without liver cirrhosis while very highly significant increased values were obtained in cirrhotic patients as compared to their corresponding values in normal group. The concentration of serum transferrin showed insignificant values in cases without liver cirrhosis whereas these values showed moderately significant decreased level in cases of liver cirrhosis. It is of interest that the values of IgA/transferrin ratio, although showed insignificant values in patients without liver cirrhosis these values were significantly high in cirrhotic patients. In addition, it has been found that in liver cirrhotic patients the mean values of IgA/transferrin ratio were nearly 2.5 times as compared to the ratios in normal or non-cirrhotic patients. From the present study, the determination of IgA and transferrin in serum or plasma may open up a very simple and safe way for the early detection of latent cirrhosis. IgA/transferrin>2.5 ratio was found to be significantly increased in latent cirrhosis as compared to patients without cirrhosis or normal subjects. This value can be considered as an indicator of latent cirrhosis in children associated with liver diseases

Lipid profile in smokers and non-smokers associated with pulmonary emphysema

The changes in lipid profile and lipid peroxidation in smoking and non-smoking subjects associated with emphysema and their effects on heart were investigated. Forty male subjects were selected and classified clinically into four groups; control, cigarette smoking subjects without emphysema, non-smoking subjects with emphysema, and cigarette smoking subjects with emphysema. Serum thiobarbituric acid reactive substances [TBARS] were assessed as a direct indicator of lipid peroxidation. Serum total lipid, total cholesterol, triglycerides, high density lipoprotein-cholesterol [HDL-C], and low density lipoprotein-cholesterol [LDL-C] were evaluated. Serum creatine kinase [CK] activity was assessed as a direct indicator of heart injury. Serum alpha-1-antitrypsin [AAT] level was measured as an indicator of emphysema. As compared to control, emphysematous and non-emphysematous groups showed alteration in lipid profile including significant increase in all lipid components, except HDL-C. In comparison with smoking group without emphysema, all lipid components revealed no significant change in non-smoking subjects with emphysema, while a sign of lipid impairments was high in cigarette smoking group with emphysema as compared to smoking group without emphysema. The level of TBARS and CK activity were higher in the two groups with emphysema as compared to either controls or smoking subjects without emphysema. In contrast, the AAT levels were low in the two groups with emphysema as compared to controls and smoking subjects without emphysema. It is clear from the foregoing findings that emphysema, especially in smoking subjects, was mainly associated with oxygen- derived free radicals that damage lipids in peribronchiolar alveoli of the lung tissues accompanied with elevation in total lipid, triglyceride, total cholesterol, LDL-C levels, that may lead to the high risk of heart diseases