Nutrition & Metabolism | |
Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats | |
Sultan El-Shehry1  Ahmed Rady1  Ibrahim M Alhazza3  Samir AE Bashandy4  Hossam Ebaid2  | |
[1] Department of Zoology, College of Science, King Saud University, KSA, P.O.Box, 2455, Riyadh, 11451, Saudi Arabia;Department of Zoology, College of Science, El-Minia University, El-Minia, Egypt;Fetal Programming of Disease Research Chair, King Saud University, KSA, Riyadh, Saudi Arabia;Department of Pharmacology, National Research Center, Cairo, Egypt | |
关键词: Anti-inflammatory effects; Oxidative stress; Akt1; Folic acid; Melatonin; Hepatic injury-markers; | |
Others : 852107 DOI : 10.1186/1743-7075-10-20 |
|
received in 2012-09-29, accepted in 2013-01-22, 发布年份 2013 | |
【 摘 要 】
This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-γ), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-α) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.
【 授权许可】
2013 Ebaid et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140719021024515.pdf | 1727KB | download | |
Figure 2. | 185KB | Image | download |
Figure 1. | 244KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Brattin WJ, GlendeJr EA, Recknagel RO: Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med 1985, 1:27-38.
- [2]Rikans LE, Hornbrook KR, Cai Y: Carbon tetrachloride hepatotoxicity as a function of age in female Fischer 344 rats. Mech Ageing Dev 1994, 76:89-99.
- [3]Sheweita SA, El-Gabar MA, Bastawy M: Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: role of antioxidants. Toxicology 2001, 169:83-92.
- [4]Sagai M, Tappel AI: Effect of vitamin E on carbon tetrachlorideinduced lipid peroxidation as demonstrated by in vivo pentane production. Toxicology Lett. 1978, 2:149-155.
- [5]Letelier ME, Jara-Sandoval J, Molina-Berríos A, Faúndez M, Aracena-Parks P, Aguilera F: Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism. Chem Biol Interact 2010, 185:208-214.
- [6]Ackermann K, Stehle JH: Melatonin synthesis in the human pineal gland: advantages, implications, and difficulties. Chronobiol Int 2006, 23:369-379.
- [7]Simonneaux V, Ribelayga C: Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 2003, 55:325-395.
- [8]Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z: Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol 2003, 50:1129-1146.
- [9]Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ: Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 2004, 36:1-9.
- [10]Cuesta S, Kireev R, García C, Forman K, Escames G, Vara E, Tresguerres JA: Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model. Mech Ageing Dev 2011, 132:573-582.
- [11]Cuesta S, Kireev R, Forman K, García C, Escames G, Ariznavarreta C, Vara E, Tresguerres JA: Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8). Exp Gerontol 2010, 45:950-956.
- [12]Gitto E, Romeo C, Reiter RJ, Impellizzeri P, Pesce S, Basile M, Antonuccio P, Trimarchi G, Gentile C, Barberi I, Zuccarello B: Melatonin reduces oxidative stress in surgical neonates. J Pediatr Surg 2004, 39:184-189.
- [13]Hsu JT, Kuo CJ, Chen TH, Wang F, Lin CJ, Yeh TS, Hwang TL, Jan YY: Melatonin prevents hemorrhagic shock-induced liver injury in rats through an Akt-dependent HO-1 pathway. J Pineal Res 2012, 53(4):410-416.
- [14]Verhaar MC, Stroes E, Rabelink TJ: Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 2002, 22:6-13.
- [15]Manzoor M, Runcie J: Folate-responsive neuropathy: report of 10 cases. Br Med J 1976, 1:1176-1178.
- [16]Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM: Folate levels and neural tube defects.Implications for prevention. JAMA J Am Med Assoc 1995, 274:1698-1702.
- [17]Duthie SJ, Narayanan S, Brand GM, Pirie L, Grant G: Impact of folate deficiency on DNA stability. J Nutr 2002, 132:2444S-2449S.
- [18]Nakano E, Higgins JA, Powers HJ: Folate protects against oxidative modification of human LDL. Br J Nutr 2001, 86:637-639.
- [19]Moens AL, Champion HC, Claeys MJ, Tavazzi B, Kaminski PM, Wolin MS, Borgonjon DJ, Van Nassauw L, Haile A, Zviman M, Bedja D, Wuyts FL, Elsaesser RS, Cos P, Gabrielson KL, Lazzarino G, Paolocci N, Timmermans JP, Vrints CJ, Kass DA: High-dose folic acid pretreatment blunts cardiac dysfunction during ischemia coupled to maintenance of high-energy phosphates and reduces postreperfusion injury. Circulation 2008, 117:1810-1819.
- [20]Solini A, Santini E, Ferrannini E: Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects. Int J Obes (Lond) 2006, 30:1197-1202.
- [21]Rizzo P, Raffone E, Benedetto V: Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles, A prospective clinical trial. Eur Rev Med Pharmacol Sci 2010, 14:555-561.
- [22]Fournier I, Ploye F, Cottet-Emard JM, Brun J, Claustrat B: Folate deficiency alters melatonin secretion in rats. J Nutr 2002, 132:2781-2784.
- [23]Makni M, Chtourou Y, Fetoui H, Garouiel M, Boudawara T, Zeghal N: Evaluation of the antioxidant, anti-inflammatory and hepatoprotective properties of vanillin in carbon tetrachloride-treated rats. Eur J Pharmacol 2011, 668:133-139.
- [24]Malek FA, Möritz KU, Fanghänel J, Bienengräberc V: Reduction of procarbazine-induced cleft palates by prenatal folic acid supplementation in rats. Pathol Res Pract 2004, 200:33-40.
- [25]Okhawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979, 95:351-358.
- [26]Moron MS, Depierre JW, Mannervik B: Levels of GSH, GR and GST activities in rat lung and liver. Biochim Biophys Acta 1979, 582:67-78.
- [27]Aebi H: Catalase in vitro. Method Enzymol 1984, 105:121-126.
- [28]Subramanian P, Mirunalini S, Pandi-Perumal SR, Trakht I, Cardinali DP: Melatonin treatment improves the antioxidant status and decreases lipid content in brain and liver of rats. Eur J Pharmacol 2007, 571:116-119.
- [29]Hwang SY, Siow YL, Au-Yeung KK, House JOK: Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney. Am J Physiol Renal Physiol 2010, 300:F189-F198.
- [30]Ebaid H, Salem A, Sayed A, Metwalli A: Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats. Lipids Health Dis 2011, 10:235.
- [31]Basu S: Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003, 189:113-127.
- [32]Ramaiah SK, Rittling S: Role of osteopontin in regulating hepatic inflammatory responses and toxic liver injury. Expert Opin Drug Metab Toxicol 2007, 3:519-526.
- [33]Niemela O, Parkkila S, Yla-Herttuala S, Halsted C, Witztum JL, Lanca A, Israel Y: Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation. Lab Invest 1994, 70:537-546.
- [34]Reiter RJ: Melatonin: lowering the high price of free radicals. News Physiol Sci 2000, 15:246-250.
- [35]Vitaglione P, Morisco F, Caporaso N, Fogliano V: Dietary antioxidant compounds and liver health. Crit Rev Food Sci Nutr 2004, 44:575-586.
- [36]Kadiska MB, Gladen BC, Baird DD, Dikalov AE, Sohal RS, Hatch GB, Jones DP, Mason RP, Barret JC: Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl4 poisoning? J Free Rad Biol Med 2000, 28:838-845.
- [37]Paulis L, Simko F: Blood pressure modulation and cardiovascular protection by melatonin: potential mechanisms behind. Physiol Res 2007, 56:671-684.
- [38]Comporti M: Three models of free radical-induced cell injury. Chem Biol Interact 1989, 72:1-56.
- [39]Lim Y, Levy M, Bray TM: Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice. J Nutr 2004, 134:811-816.
- [40]Cheh N, Chipitsyna G, Gong Q, Yeo CJ: Arafat HA: Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB (Oxford) 2009, 11:373-381.
- [41]Bassiouny AR, Zaky A, Kandeel KM: Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats. Ann Hepatol 2011, 10:516-530.
- [42]Mita A, Hashikura Y, Tagawa Y, Nakayama J, Kawakubo M, Miyagawa S: Expression of Fas ligand by hepatic macrophages in patients with fulminant hepatic failure. Am J Gastroenterol 2005, 100:2551-2559.
- [43]Zhang L, Wang X, Zheng W, Shi M: The effects of interleukin-10 on the expression of Fas and FasL in rat hepatic stellate cells. Med Chem 2006, 2:611-616.
- [44]Nagata S: Apoptosis by death factor. Cell 1997, 88:355-365.
- [45]Recknagel RO, Glende EA, Dolak JA, Waller RL: Mechanisms of carbon tetrachloride toxicity. Pharmacol. Therapeut. 1989, 43:139-154.
- [46]Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, Gilbert C, Coffer P, Downward J, Evan G: Suppression of c-Myc-induced apoptosis by Rassignalling through PI (3)K and PKB. Nature 1997, 385:44-548.
- [47]Huang FZ, Deng G, Liu XY, Luo CQ: Akt gene therapy for cirrhotic rats with portal hypertension. Zhong Nan Da XueXueBao Yi Xue Ban 2008, 33:31-37.
- [48]Ezell SA, Polytarchou C, Hatziapostolou M, Guo A, Sanidas I, Bihani T, Comb MJ, Sourvinos G, Tsichlis PN: The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY. Proc Natl Acad Sci U S A 2012, 109:E613-E621.
- [49]Kaur S, Sassano A, Dolniak B, Joshi S, Majchrzak-Kita B, Baker DP, Hay N, Fish EN, Platanias LC: Role of the Akt pathway in mRNA translation of interferon-stimulated genes. Proc Natl Acad Sci U S A 2008, 105:4808-4813.
- [50]Kane LP, Andres PG, Howland KC, Abbas AK, Weiss A: Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines. Nat Immunol 2001, 2:37-44.
- [51]Chan TY, Tang PL: Effect of melatonin on the maintenance of cholesterol homeostasis in the rat. Endocrinol. Res. 1995, 21:681-696.
- [52]Muller-Wieland D, Behnke B, Koopmann K, Krone W: Melatonin inhibits LDL receptor activity and cholesterol synthesis in freshly isolated human mononuclear leucocytes. Biochem Biophys Res Commun 1994, 202:416-421.
- [53]Dietschy JM: Theoretical considerations of what regulates low-density lipoprotein and high-density lipoprotein cholesterol. Am J Clin Nutr 1997, 65:1581S-1589S.
- [54]Marucci L, Alpini G, Glaser SS, Alvaro D, Benedetti A, Francis H, Phinizy JL, Marzioni M, Mauldin J, Venter J, Baumann B, Ugili L, LeSage G: Measurement of catalytic levels of enzymes. Part2. IFCC method for aspartate aminotransferase. J Clin Chem Clin Biochem 2002, 24:497-510.
- [55]Gomez TS, Hamann MJ, McCarney S, Savoy DN, Lubking CM, Heldebrant MP, Labno CM, McKean DJ, McNiven MA, Burkhardt JK, Billadeau DD: Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nat Immunol 2005, 6:261-270.
- [56]Fuse S, Zhang W, Usherwood EJ: Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the recall response. J Immunol 2008, 180:1148-1157.