Vol.5 No.2 – 10 : Citicoline Ameliorates Neuro- and Genotoxicity Induced by Acute Malathion Intoxication in Rats

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By: Asmaa F. Galal1*, Lamiaa M. Salem2, Mahrousa M. Hassanane2, Somaia A. Nada3,  Omar M. E. Abdel-Salam1 

1 Narcotics, Ergogrnics and Poisons Department, National Research Centre, Giza, Egypt. Affiliations ID: 60014618.

2Department of Cell Biology, National Research Centre, Giza, Egypt. Affiliations ID: 60014618.

3 Pharmacology Department, National Research Centre, Giza, Egypt. Affiliations ID: 60014618.

Abstract

Objective: In the present study, we explored the therapeutic potential of citicoline in preventing malathion induced neurotoxicity and genotoxicity. Citicoline has been shown to act as a neuroprotective in experimental animal models of ischemia and other types of brain injuries.Methods: Acute malathion intoxication was induced by intraperitoneal injection of malathion (150 mg/Kg, once per day) for two successive days. Citicoline was co-administered in three doses (100, 200, 300 mg/kg, p.o.). Serum Butyrylcholine esterase (BChE) and Paroxonase-1 (PON-1) were assessed as exposure biomarkers. Oxidative stress biomarkers were assessed in different brain region (cortex, striatum, and subcortex) in addition to TNF-α. Genotoxicity was tested by chromosomal aberrations, mitotic index, DNA fragmentation, and micronucleus tests. Results: Malathion administration resulted in marked suppression of serum BChE and PON-1 activities. Also, the exposure  to the pesticide led to elevated malondialdehyde (MDA), nitric oxide (NO) and decreased reduced glutathione (GSH) levels in investigated brain regions in addition to elevated striatal tumor necrosis factor-α (TNF-α) level. Malathion also caused profound structural chromosomal aberrations, increased liver DNA fragmentation and mitotic index. These effects were alleviated with administration of citicoline dose dependently. Conclusion: Our data indicate that citicoline can protect against malathion neurotoxic and genotoxic potential, possibly through antioxidant, anti-inflammatory activities and restoring energy stores.

Citicoline Ameliorates Neuro- and Genotoxicity Induced by Acute Malathion Intoxication in Rats-converted

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Vol.5 No.2 – 9 : Berberine attenuates cancer cell growth via modulating the cell cycle dynamics but not apoptosis in human colorectal HCT-116 3D spheroid model

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By: Ahmed A. Soffar

Division of Molecular Biology, Department of Zoology, Faculty of Science,

Alexandria University, Alexandria, Egypt

Abstract

Colorectal carcinoma is a cosmopolitan type of cancer with poor prognosis, motivating seeking novel strategies to prevent disease development and progression. The poor prognosis is attributed to the severe toxic side effects of the current therapeutic regimes. Hence, novel less toxic treatment strategies are urgently warranted. Berberine is a natural compound with several biological and pharmacological properties, including anti-fungal, anti-diabetic, cardioprotective effects. Some reports showed that berberine inhibits cell growth by inducing cell cycle arrest and promotion of apoptosis in cancer cells. Importantly, the anticancer potential of berberine in colorectal cancer has not been previously investigated. Hence, this work aims to investigate whether berberine possess anticancer properties against colorectal HCT116 cancer cells. The potential effect of berberine on cell cycle regulation and apoptosis will also be deeply investigated. This work was conducted using the more physiological 3D spheroid culture model that mimics better the impact of the tumor microenvironment as well as the cell-cell interaction in the cellular response to therapy. When compared to the previous studies, this work will explain the mode of action of berberine in more physiological conditions that better mimics the in vivo situation. In order to achieve the goal of this work, spheroid growth assay as well as proliferation assay were performed. Spheroid cell suspensions were further investigated using flow cytometry to assess the cell cycle distribution of cells upon berberine application. BrdU immunostaining was performed to elucidate the S-phase fraction of cells. The proliferation potential and the level of apoptosis were also investigated by Ki67 and Annexin V labelling, respectively. The results showed that berberine attenuated tumor spheroid growth and limits the proliferative capacity of HCT116 cells. This could be attributed to the berberine-mediated G1-phase cell cycle delay. The S-phase fraction of cells was significantly decreased upon berberine application. Unexpectedly, berberine did not induce a significant difference in the % of apoptotic cell fraction of cells as compared to the controls. Collectively, these results suggest that berberine possesses an anti-tumor efficacy in 3D culture preparations via modulating the cell cycle progression. Specifically, berberine induces G1-phase cell cycle delay and decreases the S-phase fraction of cells. Thus, it limits the proliferative capacity of cells. Also, berberine did not induce programmed cell death in the HCT116 spheroids.


Berberine attenuates cancer cell growth via modulating the cell cycle dynamics but not apoptosis in human colorectal HCT-116 3D spheroid model-converted

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Vol.5 No.2 – 8 : The curative effect of Cymbopogon citrates volatile oil against chlorambucil drug toxicity

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By: ZakariaTeleb1, KamiliaTaha2, Sobhy Hassab El-Nabi3, Islam El-Garawani3, Gouda T. Dawoud2, Samraa S. El-Shafey3 and Hanaa M. El-Esawy3

1 Department of Biochemistry, National Organization for Drug Control and Research, MHP, Egypt.

2 Department of Phytochemistry, National Organization for Drug Control and Research, MHP, Egypt

3 Department of Zoology, Faculty of Science, Menoufia University, Egypt.

Abstract

Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent and immunosuppressant. CLB mutagenicity, teratogenicity and carcinogenicity are indicated based on their structure and clinical history. This study aims to evaluate the antigenotoxic effect of Cymbopogon citratus essential oil, CC, (75 mg/kg) against CLB (7.5 mg/kg) genotoxicity in rats. GC/MS for essential oil has identified 19 compounds representing approximately 99.7% Geranial was the most abundant (53.5%) followed by Neral (35%) and Myrcene (5.3%).  The lowest was α-Muurolene (0. 1%). The marked damage was observed in total genomic DNA and total protein profile of CLB-intoxicated rat’s spleen tissues. Lymphocytes single strand breaks of treated rats were examined by comet assay after CC had ameliorated these effects in a time dependent manner (5, 10 and 15 days) for spleen and after 48 hours for lymphocytes. In conclusion, this study suggests that Cymbopogon citrates oil possesses antigenotoxic potential in CLB-intoxicated rats. It can constitute natural, new and safe co-therapeutics.

The curative effect of Cymbopogon citrates volatile oil against chlorambucil drug toxicity-converted

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