The aim of the current study was to prepare organo-modified nano montmorillonite (OMNM) and to evaluate its chemopreventive effects against the hapatonephrotoxicity induced by aflatoxin B1 (AFB1) and ochratoxin A (OA) singly or in combination in rats. OMNM was prepared using Cetyltrimethylammoniumbromide (CTAB) as organic modifier. Eighty male Sprague Dawley were divided into 8 groups and treated for 8 weeks as follow: the control group; the group treated orally with AFB1 (80 µg/kg b.w.); the group treated with OA (100 µg/kg b.w.); the group treated with AFB1 plus OA, the group treated with OMNM (5 g/kg diet) and the groups treated with AFB1 and/or OA plus OMNM. At the end of treatment period, blood and tissue samples were collected from all animals for biochemical and histological analysis. The results revealed that the expansion in the basal spacing of the montmorillonite due to the intercalation of CTAB was 7.20 Å and the average particle size of OMNM was 120 nm. The in vivo results indicated that treatment with both AFB1 and OA singly or in combination resulted in a significant increase in liver and kidney function parameters, oxidative stress and tumor markers accompanied with a significant decrease in antioxidant enzyme activities and significant histological changes in liver and kidney tissues. These changes * Corresponding author. M. A. Abdel-Wahhab et al.
22were severe in the group received the combined treatment of AFB1 and OA. OMNM alone did not show any toxic effect and it succeeded to prevent or at least diminish the toxic effects and the histological changes in liver and kidney. It can be concluded that treatment with AFB1 and OA has a synergistic toxic effects and OMNM is safe and it is a promise candidate as an additive to protect against the exposure to multi-mycotoxins in high risk population.
A new series of 1,4-benzodiazepine-2,5-dione structurally related to cyclopenin has been synthesized. The new compounds were assayed in vivo and in vitro for their ability to inhibit acetylcholinesterase enzyme and were found to have potent reversible anticholinesterase activity when tested in vitro for isolated frog rectus abdominis and guinea pig ileum in addition to increasing brain cholinesterase level in rats when percentage inhibition were tested in vivo, moreover compounds 5a, 5b, 5c and 5g were the most active. LD(50) was performed for these derivatives and they displayed high safety margin.
Background: Paracetamol exerts toxic effects on liver cells through its metabolism into N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with cellular glutathione (GSH). Once GSH is depleted, NAPQI stimulates a range of oxidative reactions that result in cell necrosis. The aim of the present investigation is to find a new strategy that would selectively protect normal hepatic tissues and sensitize liver cancer cells to the toxic effects of paracetamol or its metabolite. This may lead to the development of a targeted therapy for liver cancer. Methods: The antiproliferative effects of paracetamol and buthionine sulfoximine BSO (a glutathione depleting agent) alone and in combination on the liver cancer cells HepG2 and normal rat hepatocytes were investigated by sulphorhodamine-B assay. Effects on cell cycle regulation and induction of apoptosis were tested by flow cytometry. The level of prostaglandin expression was measured by ELISA. Results: The present study showed that both agents alone or in combination have anti-proliferative effects on both cell types. Surprisingly, BSO showed a cytoprotective effects on normal hepatocytes treated with high concentrations (1.75 and 2 mM) of paracetamol. This was confirmed by cell cycle analysis that recorded decreased fraction of sub-G1 cells indicating reduction of apoptosis in normal hepatocytes. Analysis of prostaglandin E2 revealed differential effects of paracetamol on normal and liver cancer cells. A significant increase in PGE2 level over the control was observed in normal hepatocytes whereas a significant decrease was seen in HepG2 cells after treatment with paracetamol. Conclusion: These results indicate that combination of paracetamol/BSO has
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