Amr Y. Esmat

Allied studies on the effect of Rosmarinus officinalis L. on experimental hepatotoxicity and mutagenesis

The hepatoprotective and antimutagenic effects of the rosemary essential oil and the ethanolic extract were investigated using carbon tetrachloride and cyclophosphamide as hepatotoxic and mutagenic compounds, respectively. Our results revealed that i.g. administration of the rosemary ethanolic extract (0.15 g/100 g BW) to rats for 3 weeks produced the most pronounced hepatoprotective effect compared to silymarin (reference compound) due to the amelioration of most of the studied serum and liver parameters and confirmed by histopathological examination of the liver tissue. Pretreatment of mice for 7 days with the rosemary essential oil (1.1 mg/g BW) followed by i.p. injection with cyclophosphamide reduced significantly the induced mitodepression in the bone marrow cells of the animals. The potential hepatoprotective and antimutagenic activities of the rosemary ethanolic extract and essential oil, respectively, are attributed to the presence of a relatively high percentage of phenolic compounds with high antioxidant activity (according to our chemical studies).

The antihyperlipidemic activities of 4(3H) quinazolinone and two halogenated derivatives in rats

In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.

Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats

OBJECTIVE The identification of the active phenolic compounds in the mixed extract of sea cucumber (Holothuria atra) body wall by high-performance liquid chromatography and an assessment of its hepatoprotective activity against thioacetamide-induced liver fibrosis in rats. METHODS Female Swiss albino rats were divided into four groups: normal controls; oral administration of a sea cucumber mixed extract (14.4 mg/kg of body weight) on days 2, 4, and 6 weekly for 8 consecutive weeks; intoxication with thioacetamide (200 mg/kg of body weight, intraperitoneally) on days 2 and 6 weekly for 8 wk; and oral administration of a sea cucumber extract and then intoxication with thioacetamide 2 h later for 8 wk. RESULTS High-performance liquid chromatographic analysis of the sea cucumber mixed extract revealed the presence of some phenolic components, such as chlorogenic acid, pyrogallol, rutin, coumaric acid, catechin, and ascorbic acid. In vitro studies have shown that the extract has a high scavenging activity for the nitric oxide radical, a moderate iron-chelating activity, and a weak inhibitory effect of lipid peroxidation. The subchronic oral administration of sea cucumber extract to the rats did not show any toxic side effects but increased hepatic superoxide dismutase and glutathione peroxidase activities. The coadministration of sea cucumber extract and thioacetamide (protection modality) normalized serum direct bilirubin, alanine and aspartate aminotransferases, hepatic malondialdehyde, and hydroxyproline concentrations and antioxidant enzyme activities. In addition, the histologic examination of liver sections from the protection group that were stained with hematoxylin and eosin showed substantial attenuation of the degenerative cellular changes and regressions in liver fibrosis and necrosis induced by the thioacetamide intoxication. CONCLUSION Sea cucumber mixed extract contains physiologically active phenolic compounds with antioxidant activity, which afforded a potential hepatoprotective activity against thioacetamide-induced liver injury in a rat model.

Fractionation and characterization of Cerastes cerastes cerastes snake venom and the antitumor action of its lethal and non-lethal fractions.

In the present study fractionation of the Cerastes cerastes cerastes snake venom by gel filtration on Sephadex G-75 gave 14 protein fractions. Phospholipase PLA2 activity is not uniformly correlated with the lethality to mice in regard to all venom fractions. F11 which is the richest in PLA2 activity is less toxic than F3, which contains a small amount of PLA2, and F12 is the lowest in lethality and PLA2 activity. Treatment of Ehrlich ascites-bearing mice with two i.p. injections of the most lethal fraction (F3) or a non-lethal fraction (F4) resulted in a significant antitumor activity demonstrated by an increase in the mean survival time of the animals (22.5 and 27.9 days) and in the tumor inhibition ratio of tumor growth (T/C% 139 and 172, respectively), compared to tumor-bearing controls. The cytotoxic activity of F3 and F4 against Ehrlich ascites carcinoma cells might be due to the presence of a cytotoxin rather than to the direct cytolytic effect of the PLA2 because the non-lethal F4 is free from PLA2. Treatment of Swiss albino mice with two i.p. injections of F3 or F4 at the adopted dose levels produced no detrimental side effects demonstrated by the insignificant changes in the tested serum and liver parameters. Treatment of the tumor-bearing mice with the same venom fractions significantly modulated all of the studied biochemical parameters in the serum and liver tissues, compared to normal controls.

Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice

Treatment of tumor-bearing mice with LD12.5 values of iodoacetate; IAA (1.84 mg/100 g b.w.) and/or dimethylsulphoxide; DMSO (350 mg/100 g b.w.) significantly increased the cumulative mean survival time and percentage of survivors and reduced the mean tumor weight, compared to tumor-bearing controls, however, a more pronounced effect is recorded in the combined treatment. Also, an increase in the life span (ILS%) and tumor growth inhibition ratio (T/C%) are reported and amounted to 145.78 and 43.80%, 195.54 and 61.30% and 220.77 and 78.40% in IAA, DMSO and combined-treated groups, respectively. Results obtained from biochemical studies reveal that a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls. On the other hand, a single DMSO treatment significantly elevated the activities of blood antioxidant enzymes, i.e. glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and decreased the liver RNA and DNA levels. Combined treatment increased significantly the levels of plasma LDH and erythrocytes G6PDH activities, as well as liver glycogen, and in contrast it decreased the levels of liver total protein, RNA and DNA, compared to normal controls.

Chemoprevention of prostate carcinogenesis by DFMO and/or finasteride treatment in male Wistar rats.

In the present study the chemopreventive activities of DFMO, the irreversible inhibitor of ornithine decarboxylase, and finasteride, the inhibitor of prostatic 5a-reductase, against the development of chemically induced prostate adenocarcinoma by methylnitrosourea/testosterone propionate in male Wistar rats were investigated. According to histological examination, oral administration of DFMO and finasteride, either alone or combined, for two months to MNU/TP-inoculated rats reduced the tumor incidence to 11.11%, 10% and 10%, respectively, compared to tumored controls (64.3%). DFMO and/or finasteride treatment resulted in significant reductions in the wet weight of the prostate gland and seminal vesicles and its ratio relative to the total body weight, as well as the levels of prostate total protein, DNA, RNA and DNA/RNA ratio, compared to tumored controls. However, the effect of the combined treatment was of no statistical significance compared to single DFMO or finasteride treatment, as demonstrated by the non-significant differences between the mean values of most of the studied parameters. The tumor chemopreventive activity and the prostate growth inhibitory effect of DFMO and finasteride were due to suppression of prostate polyamine synthesis. ANOVA test revealed that the relative weight of the prostate as well as blood and tissue polyamine levels could be used as significant endpoint biomarkers for DFMO and finasteride as cancer chemopreventive agents.

Biochemical changes in patients with combined chronic schistosomiasis and viral hepatitis C infections.

This study was undertaken to assess the biochemical changes induced in chronic schistosomiasis and/or chronic HCV, as well as to pinpoint the most significant parameters which could be used as dependable indices for the differentiation of single and coupled infections with or without liver cirrhosis. The selected patients were allocated into 2 broad groups: GrII (Schistosomiasis) which was subdivided into 3 subgroups: GrII(a) schistosomal patients with hepatosplenomegaly; GrII(b) hepatosplenic schistosomal patients with decompensated liver cirrhosis; GrII(c) schistosomal patients with no organomegaly. GrIII (Combined) comprised 2 subgroups: GrIII(a) schistosomal-HCV infection with decompensated liver cirrhosis; GrIII(b) schistosomal-HCV infection without liver cirrhosis. For statistical comparison normal healthy subjects were taken as a reference group (Gr I). Results showed that schistosomal patients without organomegaly manifested non significant changes in all studied parameters compared to normal controls. Highly significant elevations in serum ALT, AST, ALP and GGT activities were recorded in all other subgroups but the highest levels are reported in GrIIb. AST/ALT and direct/indirect bilirubin ratios were highest in GrIIIa (1.17 ± 0.26, 1.54 ± 0.37, respectively). Serum total protein and albumin levels showed the highest reduction (33 and 59%) concomitantly with the highest increase in γ-globulin level (75%) in GrIII(a). Blood total iron was significantly reduced in GrII(a,b) (15.6 and 12%) (8.8%) bilirubin, GGT and AST in this order are good discriminators between the different subgroups in GrII. On the other hand, ALT, AST, albumin, ALP, GGT, protein and direct bilirubin are the most significant indices to differentiate chronic schistosomiasis and the combined group with/or without liver cirrhosis.

Age Dependence of the Levels of Plasma Norepinephrine, Aldosterone, Renin Activity and Urinary Vanillylmandelic Acid in Normal and Essential Hypertensives

In the present study the upper reference limits (URLs) for resting plasma norepinephrine, epinephrine, serum aldosterone, plasma renin activity, aldosterone/renin activity ratio, as well as urinary vanillylmandelic acid in healthy Egyptian normotensive subjects over a range of ages (5-60 yr) were established. There was a significant age effect on plasma norepinephrine, UVMA, serum aldosterone and PRA, whereas a single URL for plasma epinephrine level is satisfactory. In uncomplicated untreated essential hypertensive subjects (5-60 yr), the average prevalence of elevation in the plasma norepinephrine, epinephrine and urinary vanillylmandelic acid above their corresponding URLs was 85.10, 62.15 and 83.20%, respectively. This suggests that elevation in plasma catecholamine concentrations is more likely a common consequence than playing a possible role in the pathogenesis of hypertension, supported by insignificant correlation coefficients between the plasma catecholamine levels and resting systolic and diastolic blood pressure values (SBP & DBP) in all hypertensive age groups. Primary hyperaldosteronism was not detected among the normokalemic essential hypertensives at any age using aldosterone/plasma renin activity ratio as a primary screening method. In the present study, 7 statistically significant positive coefficient correlations are reported for SBP or DBP values with UVMA levels in hypertensive children and adolescents, serum aldosterone in old hypertensives, and PRA in adult hypertensives.

Effects of Dietary Magnesium and/or Manganese Variables on the Growth Rate and Metabolism of Mice

The effects of seven feeding schedules differing only in their Mg and Mn contents on the growth rates and some metabolic aspects of Swiss albino female mice were studied. The animals were placed for 5 weeks on the seven dietary regimens and weighed weekly according to the following scheme: (1) normal diet fed (control) group; (2) Mg-deficient fed group; (3) Mn-deficient fed group; (4) coupled-deficient fed group; (5) Mg-supplemented fed group; (6) Mn-supplemented fed group, and (7) coupled-supplemented fed group. Dietary Mg and/or Mn deficiencies were found to exert unfavorable effects on the growth rate of the animals. However, dietary supplementation of Mg has a favorable influence on the growth rate of the animals. Also, several biochemical tests on the plasma and livers of the tested animals were carried out and discussed accordingly.

Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone–releasing hormone agonist

The effects of leuprorelin acetate, a luteinizing hormone‐releasing hormone agonist (LHRH‐A), on prostate carcinogenesis in probasin/SV40 Tag transgenic rat was investigated. Fifteen weeks after administration of 0.28 and 2.8 mg/kg leuprorelin, prostate weights and serum testosterone levels were significantly decreased compared to values for transgenic controls. Histopathological findings revealed that the incidence of prostatic adenocarcinomas was significantly reduced in ventral, dorsal and lateral lobes of the prostate, correlating with decreased expression of SV40 Tag oncoprotein as well as inhibition of DNA synthesis and proliferation of epithelial cells in neoplastic lesions of the ventral prostate. Microarray analysis further showed leuprorelin acetate to significantly inhibit testicular steroidogenesis, suppressing the expression of SV40 Tag oncoprotein and altering the expression of a large number of genes which might be involved in the inhibition of prostate cancer progression in this rat model. (Cancer Sci 2006; 97: 459–467)