Therapeutic Role of Secondary Metabolites from Probiotic Strains for Ehrlich Solid Tumors in Mice.

This study aimed to screen the bioactive components in Streptococcus equinus WC1 (SE-WC1) and Limosilactobacillus reuteri GM4 (LR-GM4) and estimate the therapeutic role in Ehrlich solid tumors (EST) mice model. Forty-four male albino EST mice were assigned into 7 groups and treated daily for 2 weeks, including the EST group, the EST mice that received SE-WC1 at a low or a high dose (0.5 ml *106 or 0.5 ml *108 cfu), the EST mice that received LR-GM4 at the low or the high dose (0.5 ml *106 or 0.5 ml *108 cfu), and the EST mice that received SE-WC1 plus LR-GM4 at the low or the high dose. Tumors were harvested, weighed, examined, and used for the determination of apoptosis-related gene expression. Samples of the intestine, liver, and kidney were gathered for histological examination. The GC-MS identified 24 and 36 bioactive compounds in SE-WC1 and LR-GM4, respectively. The main compound in SE-WC1 was lupeol; however, the main compound in LR-GM4 was retinaldehyde. EST mice showed disturbances in Bcl-2, Bax, and p53 mRNA expression along with histological changes in the intestine, liver, and kidney. Administration of both bacterial strains reduced the tumor weight, alleviated the disturbances in the gene expression, and improved the histological structure of the intestine, liver, and kidney in a dose-dependent. Moreover, LR-GM4 was more effective than SE-WC1 due to its higher content of bioactive compounds. It could be concluded that these strains of probiotics are promising for the treatment of solid tumors.

Evaluation of the cytotoxicity and genotoxicity potential of synthetic diacetyl food flavoring in silico, in vivo, and in vitro.

Diacetyl is a common ingredient that creates a buttery flavor in baked goods and other food products. The cytotoxic impact of diacetyl on a normal human liver cell line (THLE2) indicated an IC50 value of 41.29 mg/ml through MTT assay and a cell cycle arrest in the G0/G1 phase relative to the control. Administration of diacetyl at two-time points (acute-chronic) led to a significant increase in DNA damage indicated by the increase in tail length, tail DNA%, and tail moment. The mRNA and protein expression levels of genes in the rats' livers were then measured using real-time PCR and western blotting. The results showed an activation of the apoptotic and necrosis mechanism, with an upregulation of p53, Caspase 3, and RIP1 and a downregulation of Bcl-2 at the mRNA level. The ingestion of diacetyl disrupted the liver's oxidant/antioxidant balance, as evidenced by alterations in levels of GSH, SOD, CAT, GPx, GR, MDA, NO, and peroxynitrite. Additionally, heightened levels of inflammatory cytokines were shown. Histopathological examinations revealed necrotic foci and congested portal areas in the rats' liver cells after treatment with diacetyl. Diacetyl may interact moderately with Caspase, RIP1, and p53 core domain through In-silico, possibly resulting in upregulated gene expression.

Evaluation of the Cytotoxicity and Apoptotic Induction in Human Liver Cell Lines Exposed to Three Food Additives.

BACKGROUND: Rapid lifestyle, especially among people living in urban areas, has led to increasing reliance on the processed food market. Unfortunately, harmful effects caused by the excessive use of food additives in such type of industry are often neglected. OBJECTIVE: This proposal investigates in vitro cytotoxic and apoptotic effects of three food preservatives commonly consumed in daily meals; sodium sulphite, boric acid, and benzoic acid. METHODS: The effect of the three preservatives on cell viability was tested on two different cell lines; normal liver cell line THLE2 and human hepatocellular carcinoma cancer cell line HepG2 using MTT assay. Cell cycle arrest was measured using flow cytometry by propidium iodide. Measurement of expression levels of two central genes, p53 and bcl-2 that play key roles in cell cycle and apoptosis was carried out in HepG2 cells using real time-PCR. RESULTS: Although the effect was more significantly realized in the HepG2 cell line, the viability of both cell lines was decreased by all of the three tested compounds. Flow cytometric analysis of HepG2 cells treated with sodium sulphite, boric acid, and benzoic acid has revealed an increase in G2/M phase cell cycle arrest. In Sodium sulphite and boric acid-treated cells, expression levels of p53 were up-regulated, while that of the Bcl2 was significantly down-regulated. On the other hand, Benzoic acid has shown an anti-apoptotic feature based on the increased expression levels of Bcl-2 in treated cells. CONCLUSION: In conclusion, all of the tested compounds have decreased the cell line viability and induced both cell cycle arrest and apoptotic events indicating their high potential of being cytotoxic and genotoxic materials.