Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells

Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.

Antioxidant influence on poultry liver morphology and hepatocyte ultrastructure

Background and Aim: The poultry farming development is held back by necessity to use the concentrates with the increased number of crude protein, mycotoxicoses, and subclinical infections concentration. They make a significant impact on the liver, therefore affecting its morphofunctional condition. Antioxidants use can prevent the negative influence of these factors. This study aimed to examine the impact of feed supplements containing natural antioxidants and synthetic antioxidants. Materials and Methods: The Muscovy ducks, Hungarian White geese, and quails were the study object. Birds after hatching from eggs were split into two groups: Control and two experimental. The control group (40 birds of each species) received a normal diet in accordance with the type and age. The young ducklings, goslings, and quails of the first experimental group (30 birds of each species) received water with diisopropylammonium dichloroacetate (Dironax). The young ducklings, goslings, and quails of the second experimental group (30 birds of each species) received liquid multivitamin preparation, containing organic selenium form (Solvimin Selen) from the 1st day of the postembryonic development to the age of 60 days. We performed the weighing of the young ducklings, goslings, and quails, determined the live weight, liver weight, using the electronic scales (measurement inaccuracy is 0.02 g). To conduct the morphometric, histological, and electron microscopic studies liver, we killed the birds at the age of 1 day, 15 days, a month and 2 months during the postembryonic ontogenesis. Results: The performed overall studies allowed to determine the positive influence of the antioxidants on growth and development of the meat bird, whose body mass increased by 5-10% in comparison with the control parameters. The antioxidants use prevents the development of fatty, hydropic and parenchymal degeneration, hepatocyte and epithelial cells necrosis of the bile ducts, and connective tissue proliferation with its further fibrosis. Conclusion: This study proved that it is more effective to use well-digestible, fast-acting natural polyvitaminic antioxidant complex with selenium, starting from the 1st day of the postembryonic ontogeny.