|
1
|
Fan J, Chen CJ, Wang YC, Quan W, Wang JW, Zhang WG. Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice. World J Gastroenterol 2019; 25:1355-1365. [PMID: 30918428 PMCID: PMC6429340 DOI: 10.3748/wjg.v25.i11.1355] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 02/20/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fatty liver (FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.
AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.
METHODS Eight-week-old male C57BL/6 mice were divided into three groups randomly (control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin (HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.
RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl4 treatment. HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice on morphological examination. Hemorheological tests included whole blood viscosity (mPas, γ = 10 s-1/γ = 100 s-1) (8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ± 1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume (%) (51.00 ± 4.00, 42.00 ± 5.00, and 40.00 ± 3.00), the content of plasma fibrinase (g/L) (3.80 ± 0.50, 2.90 ± 0.80, and 2.30 ± 0.70), erythrocyte deformation index (%) (44.49 ± 5.81, 48.00 ± 15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate (mm/s per V/m) (0.55 ± 0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter (mL/min per 100 g) (94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope (μm/s) (325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02) revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller (μm) (10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79).
CONCLUSION The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.
Collapse
Affiliation(s)
- Jing Fan
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Chong-Jiu Chen
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Yu-Chen Wang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Wei Quan
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jian-Wei Wang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Wei-Guang Zhang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| |
Collapse
|
|
2
|
Ibrar M, Khan MA, Nisar M, Khan M. Evaluation of Paeonia emodi for its cardioprotective potentials: An investigative study towards possible mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2019; 231:57-65. [PMID: 30391709 DOI: 10.1016/j.jep.2018.10.041] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 08/18/2018] [Accepted: 10/31/2018] [Indexed: 05/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Paeonia emodi Wall. ex Royle (peony) is an important member of family Paeoniaceae. Different parts of the plant have been folklorically used for treatment of different diseases. Infusion of dried flowers is used to treat diarrhea, the seeds are emetic and cathartic while the rhizome has been indicated for the treatment of hysteria, abdominal spasm, nervine tonic and headache. Besides these, peony has also been used in different respiratory and cardiovascular diseases (CVDs) like hypertension, palpitations, congestive heart failure and atherosclerosis. Being a folkloric remedy for the treatment of CVDs, Paeonia emodi (P. emodi) requires to be explored scientifically for MI management. AIM The current research work was designed to explore the possible cardioprotective mechanism of P. emodi in Isoproterenol hydrochloride (ISO) induced MI in mice. MATERIALS AND METHODS Experimental animals randomly divided in different groups, received methanolic extract of P. emodi (Pe.ME) and its subsequent fractions for 15 days followed by ISO (100 mg/kg s.c) at 24 h interval for two days. The cardioprotective potential of the test samples were investigated by determining the serum levels of Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Lactate Dehydrogenase (LDH) and Creatine Phosphokinase (CPK). The ethyl acetate fraction (Pe.EA) was found potent among all the tested samples of P. emodi. Based on its high potency, Pe.EA was subjected to GC-MS analysis and further relevant experiments including anti-hyperlipidemic, antioxidant, lipid peroxidation, membrane stabilization, thrombolytic, DNA ladder assay and histopathological study. RESULTS Pe.EA exhibited significant cardioprotective activity through reduction in levels of serum biomarkers responsible for MI. It significantly reduced serum levels of ALT (p < 0.001), AST (p < 0.001), CPK (p < 0.05) and LDH (p < 0.001) at a dose of 300 mg/kg as compared to ISO treated group. The GC-MS analysis confirmed the presence of potential compounds (esculetin, methyl eugenol, isovanillic acid) which might play a role in cardioprotection. Further screening confirmed that the effect of Pe.EA is mediated through multiple targets/mechanisms, which include anti-hyperlipidemia, antioxidant, lipid peroxidation inhibition, membrane stabilization, thrombolytic and DNA protective effects. Histopathological studies revealed the palliative effect for the damage caused in myocardial tissues. CONCLUSION Findings of current study provide evidence that P. emodi is a potential candidate for the treatment and management of MI.
Collapse
Affiliation(s)
- Muhammad Ibrar
- Department of Pharmacy, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan
| | - Mir Azam Khan
- Department of Pharmacy, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan.
| | - Mohammad Nisar
- Department of Botany, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan
| | - Munasib Khan
- Department of Pharmacy, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan
| |
Collapse
|
|
3
|
Perazzoli MRA, Perondi CK, Baratto CM, Winter E, Creczynski-Pasa TB, Locatelli C. Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression. Biol Pharm Bull 2017; 40:425-434. [PMID: 28381798 DOI: 10.1248/bpb.b16-00782] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks. In both acute and chronic models, the CCl4-treated groups showed significantly increase in serum hepatic enzyme activities and histopathologic alterations, as well as a disruption in antioxidative status. In contrast, the treatment with GA and DGA restored serum hepatic enzymes activities, improved histopathologic alterations, increased glutathione (GSH) and decreased lipid peroxidation levels. The activities of liver antioxidant enzymes were increased by GA and DGA only in acute model. The expression of p53 gene increased about 3.5 times after GA and DGA treatments, which could result in cell death of damaged hepatocytes preventing of a lifelong liver failure. Thus, these results suggest that GA and DGA has the potential to prevent liver damages as the case of fibrosis condition.
Collapse
|
|
4
|
Esteban-Zubero E, Alatorre-Jiménez MA, López-Pingarrón L, Reyes-Gonzales MC, Almeida-Souza P, Cantín-Golet A, Ruiz-Ruiz FJ, Tan DX, García JJ, Reiter RJ. Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review. Pharmacol Res 2016; 105:108-120. [PMID: 26808084 DOI: 10.1016/j.phrs.2016.01.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 01/13/2016] [Accepted: 01/15/2016] [Indexed: 02/07/2023]
Abstract
The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver.
Collapse
Affiliation(s)
- Eduardo Esteban-Zubero
- Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain.
| | - Moisés Alejandro Alatorre-Jiménez
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Laura López-Pingarrón
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain
| | - Marcos César Reyes-Gonzales
- Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain
| | - Priscilla Almeida-Souza
- Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain
| | - Amparo Cantín-Golet
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain
| | - Francisco José Ruiz-Ruiz
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain
| | - Dun-Xian Tan
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - José Joaquín García
- Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain
| | - Russel J Reiter
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
| |
Collapse
|
|
5
|
Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury. Int J Biol Macromol 2014; 65:559-63. [DOI: 10.1016/j.ijbiomac.2014.02.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 01/24/2014] [Accepted: 02/03/2014] [Indexed: 11/20/2022]
|
|
6
|
Adaramoye OA, Aluko A, Oyagbemi AA. Cnidoscolus aconitifolius Leaf Extract Protects against Hepatic Damage Induced by Chronic Ethanol Administration in Wistar Rats. Alcohol Alcohol 2011; 46:451-8. [DOI: 10.1093/alcalc/agr060] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
|
|
7
|
Saravanan N, Nalini N. Effect of 2-hydroxy 4-methoxy benzoic acid on an experimental model of hyperlipidaemia, induced by chronic ethanol treatment. J Pharm Pharmacol 2010; 59:1537-42. [DOI: 10.1211/jpp.59.11.0011] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Abstract
The aim of the present study was to determine the effect of 2-hydroxy 4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India. We investigated the effect of HMBA on hyperlipidaemia induced by ethanol, exploring food intake, body weight, and hepatic and plasma lipids and lipoproteins. Male Wistar rats weighing 130–180 g were given ethanol (5 g kg−1 p.o.) daily for 30 days. Subsequently, ethanol-fed rats were given HMBA intragastrically at a dose of 200 μg kg−1 per day for 30 days. At the end of the total experimental period of 60 days, plasma concentrations of total cholesterol (CHO), triglycerides (TG), lipoproteins (LP), phospholipids (PL), free fatty acids (FFA) and lipoprotein lipase (LPL), and hepatic CHO, TG and PL were measured. Treatment of ethanol-fed rats with HMBA significantly decreased plasma CHO, TG, LP, PL and FFA and hepatic CHO, TG and PL, and increased plasma LPL concentrations compared with values in untreated ethanol-fed rats (all P < 0.05). Food intake and average body weight at the end of the experimental period were significantly increased by HMBA administration. In conclusion, administration of HMBA decreased lipids and lipoprotein concentrations significantly in an animal model of ethanol-induced hyperlipidaemia.
Collapse
Affiliation(s)
- Nadana Saravanan
- Division of Biochemistry, Rani Meyyammai College of Nursing, Annamalai University, Annamalai Nagar 602 002, Tamilnadu, India
| | - Namasivayam Nalini
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608002, Tamilnadu, India
| |
Collapse
|
|
8
|
Arulmozhi V, Krishnaveni M, Karthishwaran K, Dhamodharan G, Mirunalini S. Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity. Pharmacogn Mag 2010; 6:42-50. [PMID: 20548935 PMCID: PMC2881655 DOI: 10.4103/0973-1296.59965] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2009] [Revised: 12/07/2009] [Accepted: 02/13/2010] [Indexed: 11/20/2022] Open
Abstract
The possible protective effect of Solanum nigrum fruit extract (SNFEt) was investigated for its antioxidant and antihyperlipidemic activity against ethanol-induced toxicity in rats. The experimental animals were intoxicated with 20% ethanol (7.9 g/kg/day) for 30 days via gastric intubation. SNFEt was administered at the dose of 250 mg/kg body weight along with the daily dose of ethanol for 30 days. From the result it was observed that ethanol-induced rats showed a significant elevation in the levels of Thiobarbituric acid reactive substances (TBARS), which lowered the antioxidant defense systems, such as, reduced glutathione (GSH) and vitamins C and E, when compared to the controls. In the lipid profiles, the levels of total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL), free fatty acids (FFA), and phospholipids were significantly elevated in the ethanol-induced group, whereas, the high density lipoproteins (HDL) were found to be reduced in the plasma, and the phospholipid levels were significantly decreased in the tissues. Supplementation of SNFEt improved the antioxidant status by decreasing the levels of TBARS and altering the lipid profiles to near normal. These activities were also compared to the standard drug silymarin (25 mg/kg body weight). Thus the findings of the present study indicated a significant antioxidant and antihyperlipidemic activity of Solanum nigrum fruits, which offered protection against ethanol-induced toxicity.
Collapse
Affiliation(s)
- Vadivel Arulmozhi
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
| | - Mani Krishnaveni
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
| | - Kandhan Karthishwaran
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
| | - Ganesan Dhamodharan
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
| | - Sankaran Mirunalini
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
| |
Collapse
|
|
9
|
Kudo T, Tamagawa T, Shibata S. Effect of chronic ethanol exposure on the liver of Clock-mutant mice. J Circadian Rhythms 2009; 7:4. [PMID: 19338660 PMCID: PMC2671492 DOI: 10.1186/1740-3391-7-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2009] [Accepted: 04/01/2009] [Indexed: 01/26/2023] Open
Abstract
In humans, chronic ethanol consumption leads to a characteristic set of changes to the metabolism of lipids in the liver that is referred to as an "alcoholic fatty liver (AFL)". In severe cases, these metabolic changes result in the enlargement and fibrillization of the liver and are considered risk factors for cirrhosis and liver cancer. Clock-mutant mice have been shown to display abnormal lipid metabolism and alcohol preferences. To further understand the potential interactions between ethanol consumption, lipid metabolism, and the circadian clock, we investigated the effect of chronic ethanol intake on the lipid metabolism of Clock-mutant mice. We found that ethanol treatment produced a number of changes in the liver of Clock-mutant mice without impacting the wild-type controls. First, we found that 8 weeks of exposure to ethanol in the drinking water increased the weight of the liver in Clock-mutant mice. Ethanol treatment also increased triglyceride content of liver in Clock-mutant and wild-type mice. This increase was larger in the mutant mice. Finally, ethanol treatment altered the expression of a number of genes related to lipid metabolism in the Clock-mutant mice. Interestingly, this treatment did not impact circadian clock gene expression in the liver of either genotype. Thus, ethanol produces a number of changes in the liver of Clock-mutant mice that are not seen in the wild-type mice. These changes are consistent with the possibility that disturbance of circadian rhythmicity associated with the Clock mutation could be a risk factor for the development of an alcoholic fatty liver.
Collapse
Affiliation(s)
- Takashi Kudo
- Department of Pharmacology, School of Advanced Science and Engineering, Waseda University, Wakamatsu-cho 2-2, Shinjuku-ku, Tokyo, 162-8480, Japan.
| | | | | |
Collapse
|
|
10
|
Jeong WI, Osei-Hyiaman D, Park O, Liu J, Bátkai S, Mukhopadhyay P, Horiguchi N, Harvey-White J, Marsicano G, Lutz B, Gao B, Kunos G. Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab 2008; 7:227-35. [PMID: 18316028 DOI: 10.1016/j.cmet.2007.12.007] [Citation(s) in RCA: 241] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2007] [Revised: 11/21/2007] [Accepted: 12/17/2007] [Indexed: 12/20/2022]
Abstract
Alcohol-induced fatty liver, a major cause of morbidity, has been attributed to enhanced hepatic lipogenesis and decreased fat clearance of unknown mechanism. Here we report that the steatosis induced in mice by a low-fat, liquid ethanol diet is attenuated by concurrent blockade of cannabinoid CB1 receptors. Global or hepatocyte-specific CB1 knockout mice are resistant to ethanol-induced steatosis and increases in lipogenic gene expression and have increased carnitine palmitoyltransferase 1 activity, which, unlike in controls, is not reduced by ethanol treatment. Ethanol feeding increases the hepatic expression of CB1 receptors and upregulates the endocannabinoid 2-arachidonoylglycerol (2-AG) and its biosynthetic enzyme diacylglycerol lipase beta selectively in hepatic stellate cells. In control but not CB1 receptor-deficient hepatocytes, coculture with stellate cells from ethanol-fed mice results in upregulation of CB1 receptors and lipogenic gene expression. We conclude that paracrine activation of hepatic CB1 receptors by stellate cell-derived 2-AG mediates ethanol-induced steatosis through increasing lipogenesis and decreasing fatty acid oxidation.
Collapse
MESH Headings
- Animals
- Arachidonic Acids/metabolism
- Cannabinoid Receptor Modulators/metabolism
- Carnitine O-Palmitoyltransferase/metabolism
- Cells, Cultured
- Coculture Techniques
- Diet, Fat-Restricted
- Disease Models, Animal
- Endocannabinoids
- Ethanol
- Fatty Acid Synthases/metabolism
- Fatty Acids/metabolism
- Fatty Liver, Alcoholic/etiology
- Fatty Liver, Alcoholic/genetics
- Fatty Liver, Alcoholic/metabolism
- Fatty Liver, Alcoholic/pathology
- Fatty Liver, Alcoholic/prevention & control
- Glycerides/metabolism
- Hepatocytes/metabolism
- Lipogenesis/drug effects
- Lipogenesis/genetics
- Lipoprotein Lipase/metabolism
- Liver/drug effects
- Liver/enzymology
- Liver/metabolism
- Liver/pathology
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Oxidation-Reduction
- Paracrine Communication/drug effects
- Paracrine Communication/genetics
- Piperidines/pharmacology
- Pyrazoles/pharmacology
- Receptor, Cannabinoid, CB1/antagonists & inhibitors
- Receptor, Cannabinoid, CB1/genetics
- Receptor, Cannabinoid, CB1/metabolism
- Rimonabant
- Sterol Regulatory Element Binding Protein 1/metabolism
- Up-Regulation
Collapse
Affiliation(s)
- Won-il Jeong
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
11
|
Kunos G, Gao B. Endocannabinoids, CB1 receptors, and liver disease: hitting more than one bird with the same stone. Gastroenterology 2008; 134:622-5. [PMID: 18242226 DOI: 10.1053/j.gastro.2007.12.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
|
|
12
|
Haggarty P, Abramovich DR, Page K. The effect of maternal smoking and ethanol on fatty acid transport by the human placenta. Br J Nutr 2007. [DOI: 10.1079/bjn2001514] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas from non-smokers (n5), smokers (>ten cigarettes/d;n5) and after addition of ethanol at 2 mg/ml (n4). The maternal side was of the placenta was perfusedex vivofor 90 min with a physiological mixture of fatty acids and fatty acid:human albumin ratio. There was no effect of smoking on the transfer of linoleic (LA, 18 : 2n-6), α-linolenic (αLN, 18 : 3n-3), arachidonic (AA, 20 : 4n-6) or docosahexaenoic acid (DHA, 22 : 6n-3), expressed per perfused area (calculated from H218O exchange). However, the presence of ethanol in the perfusate at a concentration of 2 mg/ml significantly reduced (P<0·01) the absolute rate of transfer of the twon-3 polyunsaturated fatty acids, αLN and DHA. This specific effect of ethanol on αLN and DHA also resulted in an altered selectivity for transfer of individual fatty acids. In the non-smoking control group the placenta selectively transferred polyunsaturated fatty acids to the fetus in the order DHA>AA>αLN>LA. The order of selectivity was unaltered in placentas from smokers, but the addition of ethanol to the perfusion medium altered the order of selectivity to AA>αLN>LA>DHA. The presence of ethanol in the perfusate was also associated with a significant reduction (P<0·05) in the clearance of H218O. These results suggest that the presence of ethanol at a concentration of 2 mg/ml may reduce the availability of polyunsaturated fatty acids to the developing fetus.
Collapse
|
|
13
|
Maksimchik YZ, Lapshina EA, Sudnikovich EY, Zabrodskaya SV, Zavodnik IB. Protective effects of N-acetyl-L-cysteine against acute carbon tetrachloride hepatotoxicity in rats. Cell Biochem Funct 2007; 26:11-8. [PMID: 17200984 DOI: 10.1002/cbf.1382] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
In recent years, N-acetyl-L-cysteine (NAC) has been widely investigated as a potentially useful protective and antioxidative agent to be applied in many pathological states. The aim of the present work was further evaluation of the mechanisms of the NAC protective effect under carbon tetrachloride-induced acute liver injuries in rats. The rat treatment with CCl4 (4 g/kg, intragastrically) caused pronounced hepatolysis observed as an increase in blood plasma bilirubin levels and hepatic enzyme activities, which agreed with numerous previous observations. The rat intoxication was accompanied by an enhancement of membrane lipid peroxidation (1.4-fold) and protein oxidative damage (protein carbonyl group and mixed protein-glutathione disulphide formations) in the rat liver. The levels of nitric oxide in blood plasma and liver tissue significantly increased (5.3- and 1.5-fold, respectively) as blood plasma triacylglycerols decreased (1.6-fold). The NAC administration to control and intoxicated animals (three times at doses of 150 mg/kg) elevated low-molecular-weight thiols in the liver. The NAC administration under CCl4-induced intoxication prevented oxidative damage of liver cells, decreased membrane lipid peroxidation, protein carbonyls and mixed protein-glutathione disulphides formation, and partially normalized plasma triacylglycerols. At the same time the NAC treatment of intoxicated animals did not produce a marked decrease of the elevated levels of blood plasma ALT and AST activities and bilirubin. The in vitro exposure of human red blood cells to NAC increased the cellular low-molecular-weight thiol levels and retarded tert-butylhydroperoxide-induced cellular thiol depletion and membrane lipid peroxidation as well as effectively inhibited hypochlorous acid-induced erythrocyte lysis. Thus, NAC can replenish non-protein cellular thiols and protect membrane lipids and proteins due to its direct radical-scavenging properties, but it did not attenuate hepatotoxicity in the acute rat CCl4-intoxication model.
Collapse
Affiliation(s)
- Yu Z Maksimchik
- Institute of Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd., Grodno, Belarus
| | | | | | | | | |
Collapse
|
|
14
|
Avasarala S, Yang L, Sun Y, Leung AWC, Chan WY, Cheung WT, Lee SST. A temporal study on the histopathological, biochemical and molecular responses of CCl(4)-induced hepatotoxicity in Cyp2e1-null mice. Toxicology 2006; 228:310-22. [PMID: 17084009 DOI: 10.1016/j.tox.2006.09.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2006] [Accepted: 09/28/2006] [Indexed: 10/24/2022]
Abstract
Previous study using Cyp2e1-null mice showed that Cyp2e1 is required in CCl(4)-induced liver injury at 24h, what remains unclear are the temporal changes in liver damage and the spectrum of genes involved in this process. We investigated the time-dependent liver changes that occurred at morphological, histopathological, biochemical and molecular levels in both Cyp2e1(+/+) and Cyp2e1(-/-) mice after treating with either corn oil or CCl(4) (1 ml/kg) for 2, 6, 12, 24 and 48 h. A pale orange colored liver, indicative of fatty infiltration, was observed in Cyp2e1(+/+) mice treated with CCl(4) for 24 and 48 h, while the Cyp2e1(+/+) mice treated with corn oil and Cyp2e1(-/-) mice treated with either corn oil or CCl(4) showed normal reddish brown colored liver. Ballooned hepatocytes with multiple vacuoles in their cytoplasm were observed in the livers of Cyp2e1(+/+) mice 24 and 48 h after treating with CCl(4). The levels of serum alanine aminotransferase and aspartate aminotransferase, markers for liver injury, were significantly higher at 12h, peaked at 24h and gradually decreased at 48 h after CCl(4) intoxication. In contrast, this kind of damage was not apparent in the Cyp2e1(-/-) mice treated with CCl(4). Altered expressions of genes related to liver cirrhosis, apoptosis, oxidative stress, xenobiotic detoxification, lipid metabolism, chemsensory signaling or tumorigenesis, structural organization, regeneration and inflammatory response were identified, and the time-dependent changes in expression of these genes were varied. Overall, the present study provides insights into the mechanism of CCl(4)-induced hepatotoxicity in animal models.
Collapse
Affiliation(s)
- Sreedevi Avasarala
- Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | | | | | | | | | | | | |
Collapse
|
|
15
|
Nakanishi T, Oikawa D, Koutoku T, Hirakawa H, Kido Y, Tachibana T, Furuse M. Gamma-linolenic acid prevents conjugated linoleic acid-induced fatty liver in mice. Nutrition 2005; 20:390-3. [PMID: 15043857 DOI: 10.1016/j.nut.2003.12.014] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The present study was done to clarify the mechanism by which conjugated linoleic acid (CLA) induces fatty liver in mice and to attenuate this symptom by adding other dietary fatty acids. METHODS Mice were given CLA short (12 h) or long (4 wk) term or given CLA with linoleic acid (LA) or gamma-linolenic acid (GLA) in the long term (4 wk). Total lipids, triacylglycerol, and prostaglandin E(2) (PGE(2)) levels in the liver were determined. RESULTS A single administration of CLA significantly increased PGE(2) levels in the liver 12 h after administration. However, long-term administration of CLA significantly decreased the liver PGE(2) level and induced fatty liver. GLA increased PGE(2) levels, and coadministration with GLA, but not with LA, prevented the CLA-induced fatty liver. CONCLUSIONS These data suggest that CLA initially stimulates PGE(2) production followed by depletion of PGE(2) sources in the liver. The fatty liver associated with PGE(2) reduction by CLA ingestion can be attenuated by GLA in mice.
Collapse
Affiliation(s)
- Tomonori Nakanishi
- Laboratory of Advanced Animal and Marine Bioresources, Graduate School of Bioresources and Bioenvironmental Sciences, Kyushu University, Fukuoka, Japan
| | | | | | | | | | | | | |
Collapse
|
|
16
|
Hidiroglou N, Madere R. Effect of chronic ethanol consumption upon vitamine E and C tissue status in the guinea pig. Nutr Res 2000. [DOI: 10.1016/s0271-5317(00)00172-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
17
|
Aleynik SI, Leo MA, Aleynik MK, Lieber CS. Polyenylphosphatidylcholine Protects Against Alcohol but Not Iron-Induced Oxidative Stress in the Liver. Alcohol Clin Exp Res 2000. [DOI: 10.1111/j.1530-0277.2000.tb04591.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
18
|
Hidiroglou N, Madere R. Effect of chronic ethanol dosing on hepatic triglyceride and phospholipid profile and fatty acids in the guinea pig. Alcohol 1999; 19:229-33. [PMID: 10580512 DOI: 10.1016/s0741-8329(99)00051-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
An alcohol feeding study was conducted with guinea pigs to evaluate the influence of alcohol upon hepatic triglyceride and total phospholipid profile as well as phospholipid fatty acids. Twenty-seven guinea pigs were randomly assigned into four groups consisting of a control and alcohol-treated group and each group carried over a 105- or 135-day period . Alcohol was administered via the drinking water starting with a 2.5% solution (v/v) and gradually increased to 12.5% (v/v) over a 30-day period and thereafter maintained continuously for either 75 or 105 days, respectively. Control guinea pigs received glucose via the drinking water to match isocalorically the alcohol given to the test animals. At the end of the 105- and 135-day periods, animals were sacrificed and livers collected. Hepatic triglycerides were significantly elevated by alcohol dosing, whereas total phospholipid fraction remained essentially unaltered. No significant time effect was observed on hepatic triglyceride and phospholipid profiles. In ethanol-fed guinea pigs, significant increases in percentages of 18:1 n-9 and 18:2 n-6 and decreases in 16:0, 20:3 n-6 and 20:4 n-6 were observed in hepatic total phospholipid fatty acid profile compared to controls. In addition, other polyenoic acids including 22:4 n-6, 22:5 n-6, 22:5 n-3, and 22:6 n-3 were found to be highly significantly depressed in alcohol-treated animals in comparison to the controls. This study provides important baseline lipid data on guinea pig responses to ethanol and provides a starting point for the use of the guinea pig as an experimental model.
Collapse
Affiliation(s)
- N Hidiroglou
- Nutrition Research Division, Food Directorate, Health Canada, Banting Research Center, Ottawa, Ontario.
| | | |
Collapse
|
|
19
|
Guzman RE, Solter PF. Hepatic oxidative stress following prolonged sublethal microcystin LR exposure. Toxicol Pathol 1999; 27:582-8. [PMID: 10528638 DOI: 10.1177/019262339902700512] [Citation(s) in RCA: 95] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Microcystin LR (MCLR) is a naturally occurring protein phosphatase inhibitor and potent hepatotoxin produced by strains of Microcystis aeruginosa. Although its acute toxicity has been well characterized, little is known about its chronic effects. In this study, we sought to acquire evidence that oxidative stress may play a role in the pathogenesis of prolonged sublethal MCLR toxicity. Twelve rats (3 per group) weighing on average 185 g were exposed to 1 of 3 different concentrations of MCLR (16, 32, and 48 microg/kg/day) or to saline via intraperitoneal osmotic pumps for 28 days. Histologic evidence of dose-dependent hepatic inflammation was seen, including infiltration of centrilobular regions by lymphocytes, macrophages, and neutrophils, centrilobular fibrosis, apoptosis, and steatosis. Analysis of lipid peroxidation products revealed a dose-dependent increase in malondialdehyde concentrations with an approximate 4-fold increase in the livers of the high-dose rats over those of the saline-treated controls. Livers from MCLR-exposed rats were more sensitive than those of controls to the cytotoxic effects of the organic oxidizing agent tert-butyl hydroperoxide, based on an MTT (3-[dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) viability assay. These histopathologic and biochemical findings indicate that oxidative stress may play a significant role in the pathogenesis of chronic MCLR toxicosis.
Collapse
Affiliation(s)
- R E Guzman
- Department of Veterinary Pathobiology, University of Illinois, Urbana 61802, USA
| | | |
Collapse
|
|
20
|
Wong FW, Chan WY, Lee SS. Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol 1998; 153:109-18. [PMID: 9875305 DOI: 10.1006/taap.1998.8547] [Citation(s) in RCA: 190] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
CYP2E1 knockout mice (cyp2e1-/-) were used to investigate the involvement of CYP2E1 in the development of carbon tetrachloride (CCl4)-induced hepatotoxicity. Male cyp2e1-/- and wild-type (cyp2e1+/+) mice were given a single i.p. injection of 1 ml/kg (= 1.59 g/kg) CCl4 and 24 h later liver injury was assessed by elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histopathology. No significant increases in serum ALT and AST activities were observed in cyp2e1-/- mice when compared to wild-type counterparts after CCl4 exposure. No detectable abnormality in liver histology was found in cyp2e1-/- mice after CCl4 exposure. In contrast, CCl4 treatment resulted in 442- and 125-fold increases in serum ALT and AST activities, respectively, in wild-type mice. Consistent with the results of serum ALT and AST activities, severe hepatic damage was noted in livers of wild-type mice, indicating the importance of CYP2E1 in mediating the hepatic damage following CCl4 exposure in these mice. In addition, a dramatic decrease in CYP2E1-catalyzed p-nitrophenol activity and complete loss of immunoreactive CYP2E1 were observed in wild-type mice after CCl4 treatment, suggesting that CYP2E1 was degraded during the process of CCl4-induced hepatotoxicity. These studies conclusively demonstrate that CYP2E1 is the major factor involved in the CCl4-induced hepatotoxicity in mice.
Collapse
Affiliation(s)
- F W Wong
- Department of Biochemistry, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | | | | |
Collapse
|
|
21
|
Tichelaar HY, Benadé AJ, O'Keefe SJ, Jooste PL, Swanevelder SA, Van Staden E. Plasma lipids and fatty acids in urbanized Bushmen, Hereros and Kavangos of southern Africa (Namibia). Lipids 1992; 27:729-32. [PMID: 1487973 DOI: 10.1007/bf02536033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Thirty-nine urbanized ethnic Namibian people comprising 21 Bushmen (semi-urbanized), 7 Hereros and 11 Kavangos were assessed for plasma lipids and fatty acid (FA) composition. Total cholesterol and triacylglycerol concentrations were measured by enzymatic methods, and neutral lipid FA composition by gas-liquid chromatography. The results demonstrated that while total cholesterol concentrations were not significantly different, significant differences in triacylglycerol concentrations (P < 0.05) were seen between Bushmen and Kavangos. By comparing Bushmen with Hereros and Kavangos, significant differences between Bushmen and Kavangos were also observed in plasma triacylglycerol FA compositions, particularly 16:0 (32.73% vs. 25.05%), 16:1n-7 (7.00% vs. 5.06%), 18:2n-6 (9.30% vs. 22.25%) and 20:3n-6 (0.12% vs. 0.48%), while Kavangos had higher 20:4n-6 levels than Hereros (1.44% vs. 2.00%). In plasma cholesteryl esters, Bushmen were significantly different from Kavangos in 16:1n-7 (8.85% vs. 4.93%), 18:1n-9 (32.06% vs. 23.07%) and 20:4n-6 (6.91% vs. 10.00%). Significant differences were also observed between Bushmen and Hereros in 18:0 (1.08% vs. 1.29%) and 18:2n-6 (35.68% vs. 45.50%). The FA of Namibian groups were also compared with South African reference groups comprising urbanized whites and Xhosas and rural Vendas. The differences in blood lipid values can be explained primarily by excessive alcohol consumption. These results suggest that semi-urbanized Bushmen have changed their diets under urbanized conditions which may increase their risk of coronary heart disease.
Collapse
Affiliation(s)
- H Y Tichelaar
- National Research Programme for Nutritional Intervention, Tygerberg, Republic of South Africa
| | | | | | | | | | | |
Collapse
|
|
22
|
Dlugosz JW, Korsten MA, Lieber CS. The effect of the prostaglandin analogue-misoprostol on rat liver mitochondria after chronic alcohol feeding. Life Sci 1991; 49:969-78. [PMID: 1909412 DOI: 10.1016/0024-3205(91)90080-u] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding.
Collapse
Affiliation(s)
- J W Dlugosz
- Alcohol Research and Treatment Center, Bronx VA Medical Center, NY 10468
| | | | | |
Collapse
|
|
23
|
Stern Z, Korsten MA, De Carli LM, Lieber CS. Effects of arachidonic acid on hepatic lipids in ethanol-fed rats. Alcohol Clin Exp Res 1990; 14:127-9. [PMID: 2106803 DOI: 10.1111/j.1530-0277.1990.tb00459.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The effects of arachidonic acid supplementation on rats fed ethanol employing an ad libitum schedule have been reported to be different from those observed when rats are fed in more limiting, matched fashion. To reexamine this issue, rats were fed unrestricted amounts of a diet in which 36% of the energy was provided by either ethanol or isocaloric amounts of carbohydrate. In half the animals, 7% of fat consisted of arachidonic acid. Despite earlier reports to the contrary, arachidonic acid had no effect on weight gain and did not attenuate the ethanol-induced fatty liver. Arachidonate supplementation tended to increase hepatic total lipids and triacylglycerols, and to potentiate the ethanol-induced elevation of cholesterol esters. Our present results are consistent with those previously reported using pair-feeding techniques in which dietary intakes are somewhat limited. Thus, regardless of the feeding technique employed, relative arachidonic deficiency cannot be involved to explain the lipid accumulation observed after chronic ethanol consumption.
Collapse
Affiliation(s)
- Z Stern
- Section of Liver Disease and Nutrition and Alcohol Research Center, Veterans Affairs Medical Center, Bronx, New York 10468
| | | | | | | |
Collapse
|
|
24
|
Abstract
Chronic ethanol ingestion leads to hepatocellular injury and alcoholic liver disease (ALD) only if multiple factors combine to favor centrilobular hepatocellular hypoxia. It is hypothesized that these factors include a shift in the redox state, the induction of the microsomal ethanol oxidizing system (MEOS), a high blood alcohol level (BAL), a high polyunsaturated fat diet and episodic decreased O2 supply to the liver. The shift in the redox state favors a low cellular pH, decreased fatty acid oxidation and increased triglyceride formation. The increased MEOS activity increases O2 consumption and portal-central O2 gradient as well as favors acetaldehyde toxic effects including retention of hepatic lipids and export proteins causing cell swelling. The resultant increase in the concentration of acetaldehyde and lactate may stimulate fibrosis as they stimulate collagen synthesis in vitro. The resultant fatty liver narrows the sinusoids slowing sinusoid blood flow. The combination of events reduces available O2 leading to decreased levels of ATP and cellular pH making the liver vulnerable to episodes of systemic hypoxia. The role of membrane changes are reviewed, i.e., 1) membrane fluidity as related to changes in the species of phospholipids, 2) mitochondrial function as related to the changes in the lipid environment of the electron transport chain, and 3) linoleic acid-prostaglandin metabolism. Acute ethanol in vitro has been shown to affect liver cell metabolism regulation by triggering and increasing protein phosphorylation through the Ca2+-phospholipase C pathway. A high fat diet enhances the liver injury caused by chronic ethanol ingestion.
Collapse
Affiliation(s)
- S W French
- Department of Pathology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada
| |
Collapse
|
|
25
|
Cronholm T, Neri A, Karpe F, Curstedt T. Influence of dietary fats on pancreatic phospholipids of chronically ethanol-treated rats. Lipids 1988; 23:841-6. [PMID: 2846981 DOI: 10.1007/bf02536202] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Male rats were given liquid diets by pair-feeding for 24-30 days, and phosphatidylinositols in pancreas were analyzed as derivatives of diacylglycerols and fatty acids. Addition of arachidonic acid or changing the fat component (35 energy %) in the liquid diet from olive oil/corn oil to oil from Borago officinalis, which contains 22% gamma-linolenic acid, increased the fraction of arachidonoyl-containing species. This fraction was decreased by more than 50% by substituting ethanol for 36 of the 47 energy% provided by carbohydrate. A smaller difference between ethanol-fed and control rats was seen in the composition of phosphatidylcholines and phosphatidylethanolamines. There was no difference in the composition of phosphatidylinositols when fat, instead of ethanol, was used to substitute the 36 energy % in the diet containing olive oil/corn oil. Substituting ethanol for 28 of 35 energy% provided by fat as corn oil in a liquid diet had no effect on the fraction of arachidonoyl-containing species. The results indicate that the effect of ethanol on phosphatidylinositols in pancreas is not due to a deficiency of arachidonic acid, and that the effect of the ethanol-containing diet is not due to the lowered carbohydrate content. However, high contents of fat or of ethanol appear to be necessary for the effect.
Collapse
Affiliation(s)
- T Cronholm
- Department of Physiological Chemistry, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
| | | | | | | |
Collapse
|