scholarly journals TO THE MECHANISM OF SEASONAL VARIATIONS IN CARBON TETRACHLORIDE TOXICITY

2019 ◽  
Vol 98 (3) ◽  
pp. 328-331
Author(s):  
Sergey V. Skupnevskii
Keyword(s):  
Alkaline Phosphatase ◽  
Carbon Tetrachloride ◽  
Toxic Effect ◽  
Toxic Hepatitis ◽  
Malonic Dialdehyde ◽  
Biological Rhythms ◽  
Metabolic Activation ◽  
Negative Control ◽  
Male Wistar Rats

Introduction. Seasonal biorhythms can modify the toxic effect of xenobiotics. Natural fluctuations in hormone levels in the blood which can modify the metabolic processes in the liver can be the base of one of the mechanisms in this phenomenon. The study of the effector role of testosterone in seasonal chrono-reactivity can reveal one new link in the pathogenesis and will improve health risk assessment, especially in patients taking hormone therapy. The aim of the study was to reveal the role of testosterone in the mechanisms of chrono-reactivity the toxic effect for carbon tetrachloride in warm-blooded animals. Material and Methods. Studies were conducted on adult male Wistar rats, divided into negative control groups, a model with CCl4-induced toxic hepatitis, and experimental in which CCl4 exposure was carried out following a preliminary 7-day course of testosterone administration. Direct and total bilirubin, cholesterol, alkaline phosphatase, AlAT and AsAT, hydroperoxide and malondialdehyde were determined by standard methods. The experiment was repeated twice: both in winter and spring. Results. The amplitude of the damage to the structures and functions of hepatocytes from a single injection of the same poison dosage in winter and spring manifested in varying degrees, revealing the modulatory role of biological rhythms. Under premedication with testosterone, a similar tendency was observed in both series of the experiment (winter, spring): the toxic effect of CCl4 increased. This was recorded by the following biochemical changes: bilirubin increased by 55%, cholesterol - 19%, alkaline phosphatase - 12%, AlAT - 17%, AsAT - 35%, hydroperoxide - 29%, and malonic dialdehyde slightly (relative to groups with model toxic hepatitis). Conclusion. The male sex hormone regulating the metabolic activation of cytochromes in hepatocytes performing biotransformation is one of the effector links in the seasonal chrono-reactivity phenomena. The discovery of the whole mechanism will allow developing an effective system of chronoprophylaxis and reducing the risks of toxic poisoning in individuals during periods of maximum chrono-reactivity.

scholarly journals THE SEASONAL VARIATIONS OF CARBON TETRACHLORIDE TOXICITY

2019 ◽  
Vol 98 (3) ◽  
pp. 324-327
Author(s):  
V. N. Rakitskii ◽  
Sergey V. Skupnevskii
Keyword(s):  
Carbon Tetrachloride ◽  
Human Health Risk ◽  
Malonic Dialdehyde ◽  
Toxicity Testing ◽  
Biological Rhythms ◽  
Diagnostic Methods ◽  
Control Group ◽  
And Control ◽  
Metabolism Of Xenobiotics

Biological rhythms are genetically fixed as a universal form of adaptation to cyclically changing environmental factors. Many organs including the liver and body systems function in an oscillatory mode. Its central role in the process of detoxification may determine the variability of toxic effects in the metabolism of xenobiotics. The including of chronobiological patterns in the procedures of toxicological and hygienic studies will allow more accurate assessing of the properties of tested substances. The aim of the study was to identify variations in the seasonal chrono-reactivity of warm-blooded animals to the hepatotoxic effects of carbon tetrachloride. In studies there were used Wistar rats, divided into experimental (CCl4-induced toxic hepatitis) and control groups in the winter, spring, summer, and autumn. Standard laboratory diagnostic methods studied key indices characterizing the functional activity of the liver and the antioxidant status of the organism (direct and total bilirubin, cholesterol, alkaline phosphatase, ALAT, ASAT, hydroperoxide, malonic dialdehyde, catalase in the liver tissues). According to the results of the conducted research, seasonal biorhythms have a modulating effect on the organism of warm-blooded animals, and the amplitude of the detected fluctuations was observed to be wider in terms of modeled pathology. The calculation of the variation values of numerical indices shows fluctuations to take place in the range of 10-60% in control group, and within the range of 60-300% in the pathology. The most labile index was catalase. Since the mechanism of carbon tetrachloride toxicity is mediated through the initiation of lipid peroxidation, this may explain the observed phenomena of seasonal chronoreactivity. Thus, taking into account the modulating role of biorhythms in protocols for toxicity testing can optimize the currently used procedures of human health risk assessment.

scholarly journals Resveratrol Regulates Antioxidant Status, Inhibits Cytokine Expression and Restricts Apoptosis in Carbon Tetrachloride Induced Rat Hepatic Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Souvik Roy ◽  
Santanu Sannigrahi ◽  
Subhabrota Majumdar ◽  
Balaram Ghosh ◽  
Biswajit Sarkar
Keyword(s):  
Body Weight ◽  
Carbon Tetrachloride ◽  
Antioxidant Status ◽  
Hepatic Injury ◽  
Human Cancer ◽  
Oxidative Status ◽  
Hepatic Tissue ◽  
Injury Model ◽  
Male Wistar Rats

Recent studies indicate the chemopreventive role of resveratrol in many animal models like ischemia, rheumatoid arthritis, human cancer, and diabetes. The present study was designed to investigate the chemopreventive potential of resveratrol in rat hepatic injury model by carbon tetrachloride. Male Wistar rats were treated with carbon tetrachloride (0.4 g/kg body weight) intraperitoneally daily for 8 weeks. Resveratrol (100 mg/kg, 200 mg/kg body weight) was given orally from first day until the last day of experiment. The investigation assesses the effect of resveratrol on morphological, oxidative status, histopathological, immunohistochemical, and apoptotic analysis in carbon tetrachloride-challenged liver tissue. The study indicated that the inflammatory cytokines TNF-αand IL-6 were profoundly expressed in experimental rats, whereas resveratrol decreases the immunopositivity of TNF-αand IL-6 and restored the altered architectural structure of challenged hepatic tissue. Resveratrol also protects liver cells by suppressing oxidative stress and apoptosis.

scholarly journals THE INFLUENCE OF COPTISINE BISULFATE ON THE EVOLUTION OF ACUTE TOXIC HEPATITIS

World Science ◽  
2016 ◽  
Vol 2 (8(36)) ◽  
pp. 42-46
Author(s):  
Peredelcu Rodica ◽  
Gonciar Veaceslav ◽  
Scutari Corina ◽  
Cazacu Vasile
Keyword(s):  
Alkaline Phosphatase ◽  
Lactate Dehydrogenase ◽  
Carbon Tetrachloride ◽  
Toxic Hepatitis ◽  
Albumin Level ◽  
Chelidonium Majus ◽  
White Rats ◽  
Acute Toxic Hepatitis ◽  
Hepatic Cytolysis ◽  
Acute Toxic

In the experiments made on white rats was studied the influence of coptisine bisulfate, alkaloid extracted from Chelidonium majus, in the following doses: 10 mg/kg and 20 mg/kg on acute toxic hepatitis cause by carbon tetrachloride. It was established that the researched substance reduced hepatic cytolysis and cholestasis through reestablishment of the transaminases activity and lactate dehydrogenase, while lowering the alkaline phosphatase/alanine aminotransferase ratio and modulated the deflection of the metabolic parameters of acute toxic hepatitis. Coptisine bisulfate corrected the carbon tetrachloride caused hypoproteinemia when administered for 7 days and normalized the albumin level at 14th day of treatment of acute toxic hepatitis.

Role of Kupffer cells in CCl4-induced hepatocytic toxicity: A preliminary study

1993 ◽  
Vol 51 ◽  
pp. 392-393
Author(s):  
S. Yamashiro ◽  
T. Bast ◽  
R.A. Towner ◽  
E.G. Janzen ◽  
L.A. Reinke
Keyword(s):  
Kupffer Cells ◽  
Corn Oil ◽  
Cell Damage ◽  
Peroxy Radical ◽  
Metabolic Activation ◽  
Experimental Models ◽  
Male Wistar Rats ◽  
Preliminary Study ◽  
Cytochrome P 450

Carbon tetrachloride (CCl4) hepatotoxicity is one of the most frequently used experimental models to study the mechanism of cell damage by metabolites of xenobiotics (1,2). Cytochrome P-450 enzymes are considered to be involved in the metabolic activation of CCl4 to generate the trichloromethyl (.CCl3), which in turn may be converted to the peroxy radical (.00-CCl3) (3,4). In our previous studies, we have demonstrated CCl4-induced edematous response by using proton magnetic resonance imaging and electron microscopy (2,5). However, these studies have not given any consideration to Kupffer cells, which could act as an interphase between the sinusoid and hepatocytes.Three male Wistar rats (200-250 g) were given two doses of CCL4 one hour apart (160 μl/kg bodyweight, with 5% Emulphor in 0.85% saline) intraperitoneally (i.p.). The same number of rats received phenyl tert-butyl nitrone (PBN), 25 mg/200 g in a 0.07 M pH 7.4 phosphate buffer and corn oil i.p. 30 min prior to the administration of CC14 as above.

Interaction of metallothionein and carbon tetrachloride on the protective effect of zinc on hepatotoxicity

1986 ◽  
Vol 64 (8) ◽  
pp. 1104-1110 ◽  
Author(s):  
I. S. Clarke ◽  
E. M. K. Lui
Keyword(s):  
Carbon Tetrachloride ◽  
Protective Effect ◽  
Binding Capacity ◽  
Metabolic Activation ◽  
Male Rats ◽  
Chromatographic Study ◽  
Saturation Method ◽  
Hepatic Metallothionein

To study the influence of hepatic metallothionein (MT) on the hepatotoxic response to carbon tetrachloride (CCl4), adult male rats were pretreated with a 10 mg∙kg−1 dose of zinc (Zn) 24 h prior to CCl4 (i.p., 1 mL∙kg−1) treatment. Zn pretreatment increased the hepatic MT concentrations markedly and reduced the magnitudes of the CCl4-induced reduction of cytochrome P450 concentration as well as elevation of serum alanine aminotransferase and aspartate aminotransferase activities when determined at 4 or 24 h following CCl4 treatment. Treatment of Zn-exposed animals with CCl4 also resulted in significant reduction of the concentrations of hepatic MT (as determined by the cadmium-saturation method) as well as cytosolic Zn. Sephadex G-75 chromatographic study of hepatic cytosols showed that MT-bound Zn was selectively depleted by CCl4 exposure. Moreover, it was demonstrated that CCl4, after metabolic activation, reduced the cadmium binding capacity of Zn-induced hepatic MT in vitro. To examine the possible protective effect of Zn independent of induction of MT synthesis, CCl4 was administered 2 h following Zn pretreatment and the hepatotoxic response was examined 4 h later. This study revealed limited protection by Zn prior to the induction of MT synthesis. These data further support a role of MT in the modulation of CCl4 hepatotoxicity.

ROLE OF THE STROMAL CELLULAR COMPONENT IN COMPENSATORY PROCESSES IN DIFFUSE LIVER DAMAGE

2018 ◽  
pp. 32-37 ◽  
Author(s):  
Z. A. Shafigullina ◽  
S. Yu. Medvedeva ◽  
I. G. Danilova
Keyword(s):  
Toxic Hepatitis ◽  
Intraperitoneal Administration ◽  
Sharp Decrease ◽  
Cellular Component ◽  
Ki 67 ◽  
Sinusoidal Cells ◽  
Toxic Damage ◽  
Stromal Component ◽  
Regeneration Processes

The aim of the study was to assess the role of the cellular component of the stroma in liver regeneration after its toxic damage. The experimental model of toxic hepatitis caused by intraperitoneal administration of tetrachloromethane (CCl4) showed that regeneration processes in the liver on the 3rd day are manifested in an increase in binuclear hepatocytes, Ki-67 + cells and hepatocytes dividing by mitosis. The reaction of the stromal component is expressed in an increase in the number of CD45 +, mast and sinusoidal cells (SC). On the 7th day of the development of toxic hepatitis the hepatocyte alteration increases, that is accompanied by a sharp decrease in the mitotic index and the number of Ki-67 + cells. In the stromal component there is a decrease in the number of sinusoidal cells, CD45 + and a significant increase in mast cells with a high secretion granule content.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

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