Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicana extracts

Elvia Coballase-Urrutia; Noemí Cárdenas-Rodríguez; María Carolina González-García; Eithan Núñez-Ramírez; Esaú Floriano-Sánchez; María Eva González-Trujano; Berenice Fernández-Rojas; José Pedraza-Chaverrí; Hortencia Montesinos-Correa; Liliana Rivera-Espinosa; Aristides Iii Sampieri; Liliana Carmona-Aparicio

doi:10.1016/j.jsps.2016.06.008

Biochemical and molecular modulation of CCl₄-induced peripheral and central damage by Tilia americana var. mexicana extracts

Saudi Pharm J. 2017 Mar;25(3):319-331. doi: 10.1016/j.jsps.2016.06.008. Epub 2016 Jul 12.

Affiliations

¹ Laboratory of Neuroscience, National Institute of Pediatrics, 04530 D.F. Mexico, Mexico.
² Military School of Graduate of Health, Multidisciplinary Research Laboratory, SEDENA, 11270 D.F. Mexico, Mexico.
³ Laboratory of Neuropharmacology of Natural Products, National Institute of Psychiatry Ramon de la Fuente Muñiz, 14370 D.F. Mexico, Mexico.
⁴ Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04150 D.F. Mexico, Mexico.
⁵ Service of Endocrinology, National Institute of Pediatrics, 04530 D.F. Mexico, Mexico.
⁶ Laboratory of Pharmacology, National Institute of Pediatrics, 04530 D.F. Mexico, Mexico.
⁷ Department of Comparative Biology, Faculty of Sciences, National Autonomous University of Mexico, 04150 D.F. Mexico, Mexico.

Abstract

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl₄-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl₄-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl₄-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

Keywords: ALB, serum albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Ac.E, ethyl acetate extract group; Antioxidant; Aq.E, aqueous extract group; Aq.E + CCl4, aqueous extract-CCl4 group; BACT, β-actin; BB, total bilirubin; CAT, catalase; CCl3OO•, trichloromethylperoxy radical; CCl4, carbon tetrachloride; CCl4-induced damage; CDNB, 1-chloro-2,4-dinitrobenzene; CK, creatine kinase; COX-2, cyclooxygenase; CREA, creatinine; DMPO, 5,5-dimethyl-1-pyrrolin-N-oxide; EDTA, ethylenediaminetetraacetic acid disodium salt; G6PDH, glucose-6-phosphate dehydrogenase; GAPDH, glyceraldehyde-3 phosphate dehydrogenase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; GST, glutathione-S-transferase; H2O2, hydrogen peroxide; HO-1, heme oxygenase-1; He.E, hexane extract group; He.E + CCl4, hexane extract-CCl4 group; Hepatoprotective effects; MDA, malondialdehyde; Me.E, methanol extract group; Me.E + CCl4, methanol extract-CCl4 group; NADPH, nicotinamide adenine dinucleotide phosphate; NBT, nitro blue tetrazolium; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Neuroprotective effects; Nrf2, nuclear factor erythroid-derived 2-like 2; O.O, olive oil group; Oxidative stress; PPARγ, peroxisome proliferator-activated receptor gamma; RNA, ribonucleic acid; ROS, reactive oxygen species; SOD, superoxide dismutase; SOD1, superoxide dismutase-1; SOD2, superoxide dismutase-1; TNF-α, tumor necrosis factor; Tilia americana var. mexicana; UK, United Kingdom; USA, United States of America; Var., variant; [Formula: see text], trichloromethyl; bp, base pair; i.p., intraperitoneal administration; iNOS, inducible nitric oxide synthase; oxo8-dG, 8-hydroxy-2′-deoxyguanosine; γ-GLOB, γ-globulin.