To evaluate the cytotoxicity effects of luteolin (LUT) and kaempferol (KAE) via reactive oxygen species (ROS) mediated mitochondrial targeting on hepatocytes obtained from the liver of hepatocellular carcinoma (HCC) rats. In this study, HCC induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF). In the following, rat liver hepatocytes and mitochondria were isolated and tested for every eventual apoptotic and anti-HCC effects of LUT and KAE. The results of MTT assay showed that LUT and KAE were able to induce selective cytotoxicity in hepatocytes of HCC group in a dose- and time-dependent manner. Treatment of mitochondria from hepatocytes of HCC group with LUT and KAE were accompanied by loss of mitochondrial membrane potential (MMP) and mitochondrial swelling and release of cytochrome c (P < 0.001) via reactive oxygen species (ROS) generation before cytotoxicity ensued. LUT and KAE also increased activation of caspase-3 (P < 0.001 and P < 0.01, respectively). Flow-cytometry analysis indicated that the mode of cell death induced by these flavonoids were mostly apoptosis. Importantly, LUT and KAE were nontoxic for healthy hepatocytes and mitochondria. Therefore, we suggest that LUT and KAE are a good candidate for the complementary therapeutic agent against HCC.
This study investigated the influence of pulsed low-level laser therapy (LLLT) on the healing of a third-degree burn in a rat model. Two third-degree burns (distal and proximal) were made in the skin of 74 rats. Rats were divided into four groups. In group 1, the distal burn received LLLT with laser switched off; in groups 2 and 3, distal burns were treated with a 3,000 Hz-pulsed infrared diode laser with 2.3 and 11.7 J/cm 2 energy densities, respectively. In group 4, the distal burns were treated topically with 0.2% nitrofurazone. The proximal burn of all groups was considered a control burn. We assessed the response to treatment both microbiologically and macroscopically. The chi-square test showed that the incidence of Staphylococcus epidermidis, Lactobacillus, and diphtheria decreased significantly in laser-treated groups compared with other groups. Independent sample t-test showed that LLLT with 11.7 J/cm 2 energy density significantly increased wound-closure rate at 3 and 4 weeks after burning compared with their relevant control burns (p = 0.018 and p = 0.01, respectively). Pulsed LLLT with 11.7 J/cm 2 /890 nm of a third-degree burn in a rat model significantly increased wound-closure rate compared with control burns.
Akkermansia muciniphila
, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease.
Dracocephalum kotschyi Boiss. (Labiatae) is a native Iranian medicinal plant which has been used in combination with Peganum harmala L. as a remedy for many forms of human cancer especially leukemia and gastrointestinal malignancies. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In this investigation HCC was induced by a single intraperitoneal injection of diethylnitrosamine (DEN) in corn oil at 200 mg/kg body weight to rats. Two weeks after DEN administration, cancer development was promoted with dietary 2-acetylaminofluorene (2-AAF) (0.02%, w/w) for 2 weeks. Serum alpha-fetoprotein (AFP) concentration, serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities were also determined for confirmation of hepatocellular carcinoma induction. Then rat hepatocytes were isolated with collagen perfusion technique and tumoral hepatocytes were sorted by flow cytometry. Finally isolated mitochondria obtained from both tumoral and nontumoral hepatocytes were used for any probable toxic effect of Dracocephalum kotschyi ethanolic extract. Our results showed that D. kotschyi extract (250 µg/mL) induced reactive oxygen species (ROS) formation, mitochondrial membrane permeabilization (MMP), and mitochondrial swelling and cytochrome c release only in tumoral but not nontumoral hepatocyte. These findings propose Dracocephalum kotschyi as a promising candidate for future anticancer research.
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