Biochemical and genetic alterations of oxidant/antioxidant status of the brain in rats treated with dexamethasone: protective roles of melatonin and acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-carnitine

The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-l-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group, (2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group. Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue. The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role in modulation of neurotoxicity induced by DM.     

Efficiency of certain miscible oils and chlorpyriphos methyl insecticide against the soft scale insect,Kilifia acuminata Signoret (Homoptera: Coccidae) and their toxicities on rats

Abstract

The toxicity and efficacy of using three miscible oils; cabl-2, citrole and bio-dux and a chemical insecticide (chlorpyrifos-methyl) were studied against a soft scale insect, Kilifia acuminata (Signoret) infesting mango trees. The sub-chronic toxicity of tested chemicals on white albino rats was also studied. Considering the general mean number of K. acuminata stages after 3 months post spraying, chlorpyrifos methyl and capl-2 were the most efficient compounds followed by citrol and bio-dux in descending order. Chlorpyrifos-methyl was the most effective treatment for all months after spraying, the mean reduction percentage being 94.10, 91.63 and 92.00% while it gave the highest toxic effect after three months; 90.27, 87.84 and 89.73% reduction in infestation on pre-adult, adult and gravid female stages, respectively. Results also indicate that the general mean percent reduction in K. acuminata infestation were 82.62, 86.67, 78.87 and 89.28% in treated trees by citrole, cabl-2, bio-dux and chlorpyrifos-methyl, respectively. Citrole, bio-dux, cabl-2 and chlorpyrifos-methyl caused significant increase in WBCs counts, ALT and AST activities of treated rats after 15 and 30 days from treatment comparison with control. Changes occurring in the creatinine concentration showed a significant increase in rats treated with the tested chemicals 30 days from treatment, except in the case of bio-dux oil, while there were no significant changes after 15 days in rats treated with tested oils. On the contrary, tested chemicals caused a significant decrease in RBCs count and hemogobin values after 15 and 30 days form treatment, except in rats treated with bio-dux oil. Hemoglobin content showed no significant changes over the same periods.     

Selenium Nanoparticles Induce the Chemo-Sensitivity of Fluorouracil Nanoparticles in Breast and Colon Cancer Cells

Drug resistance is a major challenge of breast and colon cancer therapies leading to treatment failure. The main objective of the current study is to investigate whether selenium nanoparticles (nano-Se) can induce the chemo-sensitivity of 5-fluorouracil (FU)-encapsulated poly (D, L-lactide-co-glycolide) nanoparticles (nano-FU) in breast and colon cancer cell lines. Nano-Se and nano-FU were synthesized and characterized, then applied individually or in combination upon MCF7, MDA-MB-231, HCT 116, and Caco-2 cancerous cell lines. Cytotoxicity, cellular glucose uptake, and apoptosis, as well as malondialdehyde (MDA), nitric oxide (NO), and zinc (Zn) levels, were investigated upon the different treatments. We have resulted that nano-FU induced cell death in MCF7 and Caco-2 more effectively than MDA-MB-231 and HCT 116 cell lines. Moreover, nano-FU plus nano-Se potentiate MCF7 and Caco-2 chemo-sensitivity were higher than MDA-MB-231 and HCT 116 cancerous cell lines. It is relevant to note that Se and FU nano-formulations inhibited cancer cell bioenergetics via glucose uptake slight blockage. Furthermore, nano-FU increased the levels of NO and MDA in media over cancer cells, while their combinations with nano-Se rebalance the redox status with Zn increment. We noticed that MCF7 cell line is sensitive, while MDA-MB-231 cell line is resistant to Se and nano-Se. This novel approach could be of great potential to enhance the chemo-sensitivity in breast and colon cancer cells.

     

Selenium Overcomes Doxorubicin Resistance in Their Nano-platforms Against Breast and Colon Cancers

Biological Trace Element Research - Colon cancer in men and breast cancer in women are regarded as major health burdens, accounting for majority of cancer diagnoses globally. Doxorubicin (DOX)...