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ObjectiveTo determine the effect of the most commonly abused drugs (tramadol and morphine), on acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ as biomarkers of neurotoxicity.MethodsTramadol - as a weak μ opioid receptor agonist- and morphine - as opiate analgesic drugs, were chosen for the present study. Four series of experimental animals were conducted for either tramadol or morphine: control series; repeated single equal doses (therapeutic dose) series; cumulative increasing doses series and delay (withdrawal) series (96 hours withdrawal period after last administration), at time period intervals 7, 14 and 21 days. Acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ were measured in cerebral cortices of experimental rats.ResultsAcetylcholine esterase (AChE) activity in the brain cerebral cortex increased after the administration of therapeutic repeated doses of either tramadol (20 mg/kg b.w.) or morphine (4 mg/kg b.w.) in different groups. The daily intraperitoneal injection of cumulative increasing dose levels of either tramadol 20, 40 and 80 mg/kg or morphine 4, 8 and 12 mg/kg revealed a significant increase in the mean of acetylcholine esterase activities. The withdrawal groups of either tramadol or morphine showed significant decreases in their levels. Na+/K+ ATPase activity in the brain cerebral cortex of either repeated therapeutic doses of tramadol (20 mg/kg) or morphine repeated therapeutic doses (4 mg/kg) for 21 consecutive days at different intervals 7, 14 and 21 days, induced a significant decrease in the levels of Na+/K+-ATPase in all groups. Withdrawal groups showed a significant decrease in Na+/K+-ATPase level. Furthermore, the daily intraperitoneal injection of cumulative increasing dose levels of either tramadol (20, 40 and 80 mg/kg b.w.) or morphine (4, 8 and 12 mg/kg b.w.) induced significant decreases in Na+/K+-ATPase levels in all studied groups. Regarding Na+ and K+, concentrations of either repeated therapeutic doses or cumulative increasing doses at different time intervals, showed different fluctuations in their levels.ConclusionThe recorded data suggest that both drugs exert potent effects on AChE and Na+/K+-ATPase activities which could contribute to cerebral cortex malfunction including, memory deficits and the decline in cognitive function observed in chronic users.

This study evaluates the influence of estrogen hormone on the experimentally induced asthma in male mice. The animals were divided into four groups, with 20 mice in each group; group I (control mice) included mice that received no treatment, group II included mice that received intraperitoneal estrogen injection (0.25 mg/kg body weight (bw), twice on day 28 of the experiment), group III (asthmatic mice) included asthmatic mice that received intraperitoneal injection of two doses of ovalbumin (OVA; 2 µg of OVA mixed with 100 µg of aluminum potassium sulfate) on days 1 and 14 of the experiment and then challenged intranasally with a single dose of OVA (50 µg dissolved in 0.05 ml phosphate-buffered saline; PBS) on day 28 of the experiment, and group IV (asthmatic mice treated with estrogen) included asthma model male mice that received the estrogen (0.5 mg/kg bw in 40 ml PBS, twice on the day 28 of the experiment). The immunohistochemical studies observed a marked intensity of CD15 immunoreactivity in the lung tissues of asthma model mice. Physiological results recorded that the total and differential count of leukocytes in bronchoalveolar lavage fluid (BALF) of asthma model mice recorded a significant increase in the number of leukocytes especially in the number of eosinophil cells. The BALF of asthma model mice showed high levels of interleukins 4 and 5 (IL-4 and IL-5), and there was a significant decrease in both the levels of IL-4 and IL-5 in BALF of asthma model mice treated with estrogen. In conclusion, the obtained results indicated that the asthma is responsible for certain immunohistochemical and physiological alterations induced in lung tissues of mice. The administration of estrogen to asthmatic male mice could improve these changes. For this reason, the present findings support the possible role of estrogen in modulating the inflammatory effects caused by asthma in male mice and may be helpful to cure many asthmatic progressions.

Aim: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the sixth most common cancer worldwide. The resistance to chemotherapy is a major obstacle in the treatment of HCC, necessitating the discovery of additional agents. There is a growing use of anticancer complementary and alternative medicine worldwide. Therefore, the aim of present study was focused on the confirmation of the suitability and validity of the new markers which would be achieved by demonstrating their significant change and reproducible expression during disease and disease management. Methods: HepG 2 cell line was used to provide a source for HCC cells. The cell cultures were divided into 4 groups: control untreated group, 5-fluorouracil (5-FU) treated group as a standard chemotherapy for HCC (positive control) with the following doses (15.625, 31.2, 62.5, 125, 250 µg/mL), Kochia indica extract treated group with the following concentration (12.5, 25, 50, 100, 200 µg/mL) and the group treated with a combination of 5-FU and Kochia indica in different ratios. Results: Treatment with Kochia indica extract, 5-FU and the combined treatment showed a significant cytotoxicity to HepG 2 cells, with different IC 50 values, when compared to the control. Regarding toxic effect, 5-FU showed IC 50 = 237.56 µg/mL which is lower cytotoxic in compared to Kochia indica with IC 50 =120.5 µg/mL. The results also revealed that tumor cells were more resistant to 5-FU. Alternatively, the co-treatment with Kochia indica extract ameliorated the toxicity induced by 5-FU and enhanced its therapeutic potency, either by synergistic effect of both agents and/or due to its flavonoid components that may enhance the physiological properties of the cell membranes, facilitating 5-FU entrance into tumor cells. This decreased its therapeutic dose to less than 250 µg/mL by combination therapy. Conclusion: Present findings assume that Kochia indica extract co-therapy can ameliorate the side effects of 5-FU on HepG 2 by enhancing its cellular uptake.

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