Preventive Effects of Vitamin C on Diethylnitrosamine-induced Hepatotoxicity in Smp30 Knockout Mice

Abstract

Abstract. Vitamin C (L-ascorbic Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, resulting in approximately 0.7 million deaths each year, and the sixth most common malignancy worldwide (1-3). The recognized risk factors for HCC are hepatic disorder associated with steatosis, cirrhosis, viral hepatitis, alcohol, chemical agents, obesity, metabolic syndrome, and so forth (4). Despite recent advances in diagnosis and treatment, the effectiveness of therapy for HCC remains unsatisfactory, and HCC has a hidden development and a poor prognosis (5, 6). Therefore, there is an urgent requirement for novel therapeutic compounds for the treatment of patients with HCC. Many animal models of hepatocarcinogenesis have been established to examine the effects of therapeutic agents. Diethylnitrosamine (DEN) is frequently used as a hepatocarcinogenic agent in rodents (1). In our experimental model, externally visible foci were observed and measured by stereomicroscopy. It has been established that DEN induces HCC in animals with a developmental course similar to that of human HCC (7). Furthermore, DEN is an indirect alkylating agent that induces the generation of reactive oxygen species (ROS), which damage DNA through oxidation (8).Senescence marker protein-30 (SMP30) is a calciumbinding protein, and its levels in the liver, kidney, and lung become significantly down-regulated with aging in an androgen-independent manner (9, 10). SMP30 plays an important role in calcium (Ca 2+ ) homeostasis (11). Ca 2+ is one of the most universal and physiologically significant signaling molecules that especially affects cell apoptosis and cell necrosis (12). Other reports have indicated that SMP30 participates in controlling the activity of antioxidant enzymes 93

Red Ginseng Oil Attenuates Oxidative Stress and Offers Protection against Ultraviolet-Induced Photo Toxicity

“…For evaluating the histopathological changes, the liver tissues were fixed in 10% formalin and routinely processed in a graded ethanol series and toluene, as described previously [ 25 ]. The tissues were then embedded in paraffin and sectioned into 5- μ m-thick slices.…”

Ascorbate Is a Primary Antioxidant in Mammals

“…In vitro experiments using a cell line suggests that RGN exhibits anti-tumor effects through the suppression of histone deacetylase 4 (HDAC4). When diethylnitrosamine, a popular carcinogenic compound, is administered to RGN −/− mice, severe hepatic damage is observed, and, due to the high toxicity of this compound, all of the mice died before developing cancer [ 171 ].…”

Ascorbate is a multifunctional micronutrient whose synthesis is lacking in primates

“…The administration of N -nitrosodiethylamine causes the complete death in Rgn -KO mice within 4 months and therefore provides no information regarding tumorigenesis. ( 117 ) Although Akr1a -KO mice are also mostly dead within a half-year, a few surviving mice developed extreme hepatocellular carcinomas, and Asc-supplementation markedly suppressed hepatocellular carcinoma development. ( 118 ) Because methylation of cytosine in DNA and lysine residues in histones epigenetically suppresses the expression of genes that include tumor suppressor genes, their Asc-mediated demethylation may lead to their reactivation.…”