Cytotoxic Effects of Ethanolic Extract of Polypodium Vulgare on Human Malignant Melanoma Cell Line.

BACKGROUND: Melanoma is a malignant tumor that originates from the skin's melanocytes and has the highest death rate from skin cancer. Developing more efficacious anticancer medications with fewer adverse effects is the key to effective cancer management. Natural products are considered relevant and cost-effective sources of treatment. The plant (Polypodium vulgare) is a small and evergreen fern. One of the most important chemical compounds in the extract of this herb is flavonoids, which are thought to have beneficial effects in the treatment of melanoma through antioxidant properties. OBJECTIVES: Due to the limitations of current cancer management and cytotoxic drugs available in the country, the need to study drugs of natural origin has become more prominent. In this regard, the present study aims to investigate the cytotoxic effects of the ethanolic extract of Polypodium vulgare on A375 melanoma cells. METHODS: Polypodium vulgare was extracted in 80% ethanol by the maceration. Then, its effects on the cell death of the melanoma cell line A375 compared to the AGO-1522 cell line as control were measured using the MTT-assay technique. The amount of cellular lipid peroxidation was estimated by TBARS assay. The amount of cellular ROS was calculated by fluorescent reagent 2,7-dichlorofluorescein diacetate. Cytochrome c concentration was measured by a cytochrome c immunoassay kit. RESULTS: In this experiment, the anticancer effects of Polypodium vulgare ethanolic extract on human melanoma cell lines were investigated for the first time. Herb extract with a concentration of 0.123 mg/ml significantly increased the death of A375 melanoma cells (p < 0.001), lipid peroxidation (p < 0.01), and reactive oxygen species (ROS) (p < 0.01) and cytochrome c concentration (p < 0.001). Meanwhile, the same amount was ineffective and safe on AGO-1522 normal fibroblast cells. CONCLUSION: A 0.123 mg/ml concentration of Polypodium vulgare increases apoptosis in melanoma cells. Meanwhile, the same amount was safe on healthy cells. So, it could be considered an effective treatment without side effects in human melanoma.

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity.

Sofosbuvir, the oral direct-acting antiviral, is a medication, which used as the effective treatment for hepatitis C infection. Although sofosbuvir thought to have few adverse-effects, there have been some experiences of serious drug-induced hepatotoxicity. In this research, the molecular/cellular pathways that lead to sofosbuvir-induced hepatotoxicity were evaluated on isolated rat hepatocytes. Rat hepatocytes were isolated using collagenase reperfusion technique. In evaluating the different pathways of sofosbuvir-induced hepatotoxicity, ROS formation, mitochondrial membrane potential collapse, lysosomal membrane damage, glutathione depletion, and the percentage of apoptosis versus necrosis were determined. Our data demonstrated that the cytotoxic effect of sofosbuvir in lower concentrations (25, 50 and 100 µM) is mediated by above stream pathways. On the other hand, sofosbuvir acts in opposite directions at higher concentrations (400 µM) and acts as an antioxidant and hepatoprotective. We concluded that sofosbuvir while looking toxic and pro-oxidant in lower concentrations, acts as protective and antioxidant in higher concentrations.

Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review.

The liver is a vital metabolic organ for drug and xenobiotic metabolism which is influenced by chemical and natural toxins. Liver injury is associated with systemic oxidative stress, which leads to cellular necrosis, fibrosis, tissue lipid peroxidation, and depletion in glutathione levels. Considering the lack of reliable hepato-protective drugs in modern medicine, plant-derived phytoconstituents seem to be a noteworthy option. Naringin is an abundant flavonoid found in citrus fruits with various pharmacological benefits such as antioxidant, anti-inflammatory, and antiapoptotic, activities. In this review, we summarize available data from recent studies about the hepatoprotective effects of naringin against chemical toxicants and discuss the possible mechanisms of actions.