Several chemicals, including environmental toxicants and clinically useful drugs, cause severe cellular damage to different organs of our body through metabolic activation to highly reactive substances such as free radicals. Carbon tetrachloride is an organic compound of which chemical formula is CCl₄. CCl4 is strong toxic in the kidney, testicle, brain, heart, lung, other tissues, and particularly in the liver. CCl4 is a powerful hepatoxic, nephrotoxic and prooxidant agent which is widely used to induce hepatotoxicity in experimental animals and to create hepatocellular carcinoma, hepatic fibrosis/cirrhosis and liver injury, chemical hepatitis model, renal failure model, and nephrotoxicity model in recent years. The damage-causing mechanism of CCl4 in tissues can be explained as oxidative damage caused by lipid peroxidation which starts after the conversion of CCl4 to free radicals of highly toxic trichloromethyl radicals (•CCl₃) and trichloromethyl peroxyl radical (•CCl₃O2) via cytochrome P450 enzyme. Complete disruption of lipids (i.e., peroxidation) is the hallmark of oxidative damage. Free radicals are structures that contain one or more unpaired electrons in atomic or molecular orbitals. These toxic free radicals induce a chain reaction and lipid peroxidation in membrane-like structures rich in phospholipids, such as mitochondria and endoplasmic reticulum. CCl4-induced lipid peroxidation is the cause of oxidative stress, mitochondrial stress, endoplasmic reticulum stress. Free radicals trigger many biological processes, such as apoptosis, necrosis, ferroptosis and autophagy. Recent researches state that the way to reduce or eliminate these CCl4-induced negative effects is the antioxidants originated from natural sources. For normal physiological function, there must be a balance between free radicals and antioxidants. If this balance is in favor of free radicals, various pathological conditions occur. Free radicals play a role in various pathological conditions including Pulmonary disease, ischemia / reperfusion rheumatological diseases, autoimmune disorders, cardiovascular diseases, cancer, kidney diseases, hypertension, eye diseases, neurological disorders, diabetes and aging. Free radicals are antagonized by antioxidants and quenched. Antioxidants do not only remove free radicals, but they also have anti-inflammatory, anti-allergic, antithrombotic, antiviral, and anti-carcinogenic activities. Antioxidants contain high phenol compounds and antioxidants have relatively low side effects compared to synthetic drugs. The antioxidants investigated in CCI4 toxicity are usually antioxidants from plants and are promising because of their rich resources and low side effects. Data were investigated using PubMed, EBSCO, Embase, Web of Science, DOAJ, Scopus and Google Scholar, Carbon tetrachloride, carbon tetrachloride-induced toxicity, oxidative stress, and free radical keywords. This study aims to enlighten the damage-causing mechanism created by free radicals which are produced by CCl4 on tissues/cells and to discuss the role of antioxidants in the prevention of tissue/cell damage. In the future, Antioxidants can be used as a therapeutic strategy to strengthen effective treatment against substances with high toxicity such as CCl4 and increase the antioxidant capacity of cells.
Objective: It was aimed to determine the antitumor and antiproliferative activity of whey protein (whey) obtained from sheep colostrum isolation on colorectal cancer cells (Caco-2). Method: Colostrum was separated into fractions as whey proteins using the isoelectric point. Before cell culture was studied, whey protein was sterilized by a membrane filter. Antitumoral activity levels of different concentrations of lyophilized proteins were measured by MTT viability test on cells and IC50 values were determined. Results: Sheep whey proteins were incubated with Caco-2 cells for 24, 48 and 72 hours with serial dilutions starting with 3200 µg/ml and decreasing. When incubated with sheep whey Caco-2 cells, cell viability: 66.34% at 24 h; IC50 value of 8.414 µg/ml; IC50 value of 46.61% at 48 h was 5,838 µg/ml; The IC50 value of 4.61% at 72 h was found to be 4,741 µg/ml. Conclusion: It was concluded that whey proteins obtained from sheep colostrum isolation have apoptotic and anticarcinogenic effects on Caco-2 cancer cell line and significantly inhibit the growth of tumor cells. We think that the results of this study will lead to studies to be carried out in vitro.
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