The effects of carvacrol on oxidative stress, inflammation, and liver function indicators in a systemic inflammation model induced by lipopolysaccharide in rats
Abstract
Abstract: The effect of carvacrol (CAR) on oxidative stress, inflammation, and liver dysfunction induced by lipopolysaccharide (LPS) was explored. The rats (n=40) were daily injected (2 weeks) by saline as control, LPS (1 mg/kg, i.p.), and 25, 50 or 100 mg/kg CAR (i.p.) before LPS. LPS increased aspartate transaminase (AST: 162±13 U/L), alanine aminotransferase (ALT: 74.6±2.15 U/L), alkaline phosphatase (ALK-P: 811±51 U/L), interlukine-1β (IL-1β: 1254±51 pg/g tissue), malondialdehyde (MDA: 32±1.09 nM/g tissue), and nitric oxide (NO: 224±13.5 nM/g tissue) (P<0.01–P<0.001) while, decreased total protein(4.08±0.38 g/dl), albumin(2.79±0.16 g/dl), thiol (5.16±0.19 μM/g tissue), superoxide dismutase (SOD: 10.57±0.13 U/g tissue), and catalase (CAT: 0.78±0.02 U/g tissue) compared to control (P<0.001). CAR reversed the effects of LPS (P<0.05–P<0.001). In the rats treated by 100 mg/kg CAR, the indicators were as follows: AST: 118±10.1 U/L, ALT: 42.5±4.13 U/L, ALK-P: 597±39.91 U/L, IL-1β: 494±15 pg/g tissue, and NO: 141±5.35 nM/g tissue. Both 50 and 100 mg/kg CAR corrected oxidative stress indicators and in the group treated by 100 mg/kg CAR, they were: MDA: 23.4±0.91 nM/g tissue, thiol: 7.98±0.18 μM/g tissue, SOD: 21±0.8 U/g tissue, and CAT: 1.12±0.02 U/g tissue(P<0.05–P<0.001). In conclusion, CAR improved liver function, accompanied with antioxidant and antiinflammatory effects.
References
1 . The effect of omega-3 and vitamin E on oxidative stress and inflammation: Systematic review and meta-analysis of randomized controlled trials. Int J Vitam Nutr Res. 2020;90(5–6):553–63.
2 Upregulation of mitochondrial Nox4 mediates TGF-β-induced apoptosis in cultured mouse podocytes. Am J Physiol Renal Physiol. 2014;306(2):F155–67.
3 Oxidative & nitrosative stress in depression: why so much stress? Am J Physiol Renal Physiol. 2014;45:46–62.
4 . Protective effect of aminoguanidine against lipopolysaccharide-induced hepatotoxicity and liver dysfunction in rat. Drug Chem Toxicol. 2019;1–7.
5 . Protective effect against brain tissues oxidative damage as a possible mechanism for beneficial effects of L-arginine on lipopolysaccharide induced memory impairment in rats. 2018;41(2):175–81.
6 Boletus aereus protects against acute alcohol-induced liver damage in the C57BL/6 mouse via regulating the oxidative stress-mediated NF-κB pathway. Pharm Biol. 2020;58(1):905–14.
7 . High day-to-day and diurnal variability of oxidative stress and inflammation biomarkers in people with type 2 diabetes mellitus and healthy individuals. Redox Report. 2020;25(1):64–9.
8 . Reactive Oxygen Species: Drivers of Physiological and Pathological Processes. J Inflamm Res. 2020;13:1057.
9 . The reactive oxygen species in macrophage polarization: reflecting its dual role in progression and treatment of human diseases. Oxid Med Cell Longev. 2016;2016.
10 Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway. PloS one. 2016;11(6):e0157246.
11 TNF-alpha and leptin in experimental liver fibrosis models induced by carbon tetrachloride and by common bile duct ligation. Biochem Funct. 2004;22(6):359–63.
12 . Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats. Phytother Res. 2008;22(10):1372–9.
13 Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204–18.
14 . Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology. 2008;47(5):1483–94.
15 Lipopolysaccharide exposure induces oxidative damage in Caenorhabditis elegans: protective effects of carnosine. BMC Pharmacol Toxicol. 2020;21(1):1–9.
16 . Lung Epithelial TRPA1 Mediates Lipopolysaccharide-Induced Lung Inflammation in Bronchial Epithelial Cells and Mice. Front Physiol. 2020;11:1521.
17 . The role of Kupffer cells and TNF-α in monocrotaline and bacterial lipopolysaccharide-induced liver injury. Toxicol Sci. 2003;71(1):124–32.
18 . Lipopolysaccharide-induced liver apoptosis is increased in interleukin-10 knockout mice. Biochim Biophys Acta Mol Basis Dis. 2006;1762(4):468–77.
19 . Molecular mechanisms behind free radical scavengers function against oxidative stress. Antioxidants. 2017;6(3):51.
20 . Protective effects of carvacrol against oxidative stress induced by chronic stress in rat’s brain, liver, and kidney. Biochem Res Int. 2016;2016.
21 . The effect of carvacrol on healthy neurons and N2a cancer cells: some biochemical, anticancerogenicity and genotoxicity studies. Cytotechnology. 2014;66(1):149–57.
22 . Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. Eur J Pharmacol. 2013;699(1–3):112–7.
23 . Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats. Asian Pac J Trop Med. 2013;6(3):205–11.
24 . Ameliorative role of metformin on lipopolysaccharide-mediated liver malfunction through suppression of inflammation and oxidative stress in rats. Toxin Reviews. 2020;1–9.
25 Carvacrol Ameliorates Pathological Cardiac Hypertrophy in Both In-vivo and In-vitro Models. Int Immunopharmacol. 2019;18(3):1380–94.
26 The effects of anesthetic regimen in 90% hepatectomy in rats. Acta Cir Bras. 2012;27(10):702–6.
27 Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice. Int Immunopharmacol. 2012;12(4):682–8.
28 The role of the liver in the response to LPS: experimental and clinical findings. J Endotoxin Res. 2002;8(5):319–27.
29 . Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr Med Chem. 2012;19(28):4850–60.
30 . Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082.
31 . Antioxidants as therapeutic agents for liver disease. Liver Int. 2011;31(10):1432–48.
32 . Effect of alpha–Lipoic acid on LPS-induced oxidative stress in the heart. Acta Physiol Pol. 2009;60(1):61.
33 . The hepatic inflammatory response after acetaminophen overdose: role of neutrophils. Toxicol Sci. 2000;54(2):509–16.
34 . Role of caspase-1 and interleukin-1β in acetaminophen-induced hepatic inflammation and liver injury. Toxicol Appl Pharmacol. 2010;247(3):169–78.
35 . Plasminogen activator inhibitor-1 limits liver injury and facilitates regeneration after acetaminophen overdose. Toxicol Sci. 2008;104(2):419–27.
36 . Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1-and TNFR2-dependent liver toxicity in mice. Immunol Lett. 2000;74(2):165–72.
37 Importance of Kupffer cells for T-cell-dependent liver injury in mice. Am J Pathol. 2000;157(5):1671–83.
38 . Relevance of the NLRP3 inflammasome in the pathogenesis of chronic liver disease. Front Immunol. 2017;8:1728.
39 . Enzymatic antioxidant system in vascular inflammation and coronary artery disease. World J Exp Med. 2015;5(4):218.
40 . Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in lipid peroxidation. Free Radic Biol Med. 1998;24(4):511–21.
41 Carvacrol and human health: A comprehensive review. Phytother Res. 2018;32(9):1675–87.
42 . The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response. Cytotechnology. 2016;68(4):1131–46.
43 Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats. Mol Cell Biochem. 2012;360(1–2):51–60.
44 . Anticholinesterase and antioxidant effects of the ethanol extract, ethanol fractions and isolated flavonoids from Cistus laurifolius L. leaves. Food Chem. 2012;131(2):626–31.
45 . Carvacrol may alleviate vascular inflammation in diabetic db/db mice. Int J Mol Med. 2020;46(3):977–88.
46 . Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2019;98(5):2026–33.
47 Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats. Neurotox Res. 2020;37(4):965–76.
48 . Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: A randomized double-blind clinical trial. J Clin Pharm Ther. 2018;43(5):664–74.
49 . The effect of carvacrol on inflammatory mediators and respiratory symptoms in veterans exposed to sulfur mustard, a randomized, placebo-controlled trial. Respir Med. 2019;150:21–9.
50 . A double-blind, randomized, placebo-controlled clinical trial on the effect of carvacrol on serum cytokine levels and pulmonary function tests in sulfur mustard induced lung injury. Cytokine. 2019;113:311–8.