RESUMO
Virgin coconut oil (VCO), prepared from fresh coconut kernel without any chemical refining, is an emerging functional food. The pharmacological benefits of VCO are believed to be due to the natural combination of phenolics. Although cell culture studies have demonstrated the antioxidant activity of VCO under different oxidative stress conditions, a valid in vivo demonstration of the antioxidant activity of VCO is yet to come. Sodium fluoride (NaF), an environmental pollutant, is widely used to induce oxidative stress in cell culture models and rodents to test the antioxidant potential of several compounds. Herein, VCO and its polyphenolic (VCOP) and non-phenolic oil fraction (VCOF) were individually tested in fluoride-exposed normal intestinal cells (IEC-6) and mice to address their contribution to the documented antioxidant potential. It was found that pretreatment of VCOP (40 µg/mL) was effective in mitigating the fluoride-induced cell death when compared to VCO (200 µg/mL) and VCOF (160 µg/mL). Further, exposure to fluoride (10 mM), increased the intracellular ROS measured based on the dichlorofluorescein (DCF) fluorescence, and this, in turn, was significantly reduced when the cells were supplemented with VCOP. Oral administration of VCO (2 mL/kg bwt) reversed the drop in the hepatic catalase and SOD activities to near normal with a minimal level of lipid peroxidation in fluoride intoxicated mice. However, VCOP and VCOF were less effective in lowering the fluoride-induced increase in hepatic oxidative stress markers. It is reasoned that the oil components of VCO complement the natural antioxidant molecules resulting in an overall increase in their bioavailability.
Assuntos
Poluentes Ambientais , Polifenóis , Camundongos , Animais , Óleo de Coco , Polifenóis/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Fluoreto de Sódio/toxicidade , Fluoretos , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismoRESUMO
We have developed a simple, reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of bisphenol A (BPA) in thermal paper cash register receipts (CRs). The method is suitable for analysis of other types of bisphenols and it involves an overnight extraction of CRs with acetonitrile (AN) at 50 °C followed by the HPLC analysis on a Supelcosil LC18 column (150 × 4.6 mm, particle size: 5 µ) using 50% AN in water as the mobile phase (5 min, isocratic). The composition of AN in the mobile phase changed to 100% over a 10 min period (linear gradient) and then held at 100% AN for 10 min (isocratic). The flow rate was set at 1 mL/min (injection volume: 20 µL) and the eluent was monitored at 234 nm. The authentic BPA eluted with a retention time of 5.9 min and gave a linear detector response in the concentration range of 0.23-50 mg/L. BPA in the CR extracts also eluted with the same retention and had identical absorbance properties as the standard. When CR extracts were co-injected with authentic BPA, they were resolved as a single peak. Further, GC/MS/EI analysis of authentic BPA and the HPLC-purified CR extracts have identical ion chromatograms and fragmentation of the molecular ion (m/z = 228). We have analyzed 170 CRs collected from 62 different vendors including supermarkets, fast food restaurants, gas stations and banking outlets. Almost all cash receipts (n = 168) showed the presence of BPA in the concentration range of 0.45-4.26% (M ± SD, 1.54 ± 0.73%).
Assuntos
Compostos Benzidrílicos/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Papel , Fenóis/análise , Calibragem , Monitoramento Ambiental/instrumentação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Louisiana , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
At room temperature, the title salt, C7H10NO+·Cl-, is ortho-rhom-bic, space group Pbca with Z' = 1, as previously reported [Zhao (2009 â¸). Acta Cryst. E65, o2378]. Between 250 and 200â K, there is a solid-state phase transition to a twinned monoclinic P21/c structure with Z' = 2. We report the high temperature structure at 250â K and the low-temperature structure at 100â K. In the low-temperature structure, the -NH3 hydrogen atoms are ordered and this group has a different orientation in each independent mol-ecule, in keeping with optimizing N-Hâ¯Cl hydrogen bonding, some of which are bifurcated: these hydrogen bonds have Nâ¯Cl distances in the range 3.1201â (8)-3.4047â (8)â Å. In the single cation of the high-temperature structure, the NH hydrogen atoms are disordered into the average of the two low-temperature positions and the Nâ¯Cl hydrogen bond distances are in the range 3.1570â (15)-3.3323â (18)â Å. At both temperatures, the meth-oxy group is nearly coplanar with the rest of the mol-ecule, with the C-C-O-C torsion angles being -7.0â (2)° at 250â K and -6.94â (12) and -9.35â (12)° at 100â K. In the extended ortho-rhom-bic structure, (001) hydrogen-bonded sheets occur; in the monoclinic structure, the sheets propagate in the (010) plane.
RESUMO
The oxidation of me-thionyl peptides can contribute to increased biological (oxidative) stress and development of various inflammatory diseases. The conformation of peptides has an important role in the mechanism of oxidation and the inter-mediates formed in the reaction. Herein, the crystal structures of the isomeric dipeptides Gly-Met (Gly = glycine and Met = me-thio-nine) and Met-Gly, both C7H14N2O3S, are reported. Both mol-ecules exist in the solid state as zwitterions with nominal proton transfer from the carb-oxy-lic acid to the primary amine group. The Gly-Met mol-ecule has an extended backbone structure, while Met-Gly has two nearly planar regions kinked at the C atom bearing the NH3 group. In the crystals, both structures form extensive three-dimensional hydrogen-bonding networks via N-Hâ¯O and bifurcated N-Hâ¯(O,O) hydrogen bonds having Nâ¯O distances in the range 2.6619â (13)-2.8513â (13)â Å for Gly-Met and 2.6273â (8)-3.1465â (8)â Å for Met-Gly.
RESUMO
We investigated the prooxidant effects of bisphenol A (BPA) phenoxyl radicals in comparison with the phenoxyl radicals of 3-tert-butyl-4-hydroxyanisole (BHA), 2,6-di-tert-butyl-methylphenol (BHT) and 4-tert-butylphenol (TBP). The phenoxyl radicals, generated in situ by 1-electron oxidation of the corresponding phenol, were allowed to react with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and rifampicin. The antioxidant activity of various phenols was examined based on the reduction of 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). It was found that the prooxidant activity of BPA phenoxyl radicals far exceeded those of BHA and BHT of phenoxyl radicals. Unlike Trolox, BPA showed minimal DPPH scavenging activity. The strong prooxidant properties of BPA phenoxyl radicals propelled us to study the markers of cellular oxidative stress in GT1-7 hypothalamic neurons exposed to BPA. It was observed that neuronal cells exposed to BPA had increased generation of intracellular peroxides and mitochondrial superoxide ([Formula: see text]). The formation of peroxides and [Formula: see text] were time- and dose-dependent and that co-incubation with N-acetyl-l-cysteine or Trolox greatly lowered their levels. The results of the present study are consistent with emerging evidence that human populations (non-institutionalized) having higher levels of urinary BPA also have increased levels of oxidative stress markers and are prone to higher risk of cardiovascular diseases, diabetes and abnormalities in hepatic enzymes.
Assuntos
Compostos Benzidrílicos/toxicidade , Radicais Livres/toxicidade , Oxidantes/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Compostos Benzidrílicos/química , Compostos de Bifenilo/química , Hidroxianisol Butilado/química , Hidroxianisol Butilado/toxicidade , Hidroxitolueno Butilado , Técnicas de Cultura de Células , Linhagem Celular , Radicais Livres/química , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , NADP/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxidantes/química , Oxirredução , Peróxidos/metabolismo , Fenóis/química , Picratos/química , Rifampina/química , Superóxidos/metabolismoRESUMO
The structure of the title compound, C10H6N4O2, reported by Smalley et al. [(2021). Cryst. Growth Des. 22, 524-534] from powder diffraction data and 15N NMR spectroscopy, is confirmed using low-temperature data from a twinned crystal. The tautomer in the solid state is alloxazine (1H-benzo[g]pteridine-2,4-dione) rather than isoalloxazine (10H-benzo[g]pteridine-2,4-dione). In the extended structure, the mol-ecules form hydrogen-bonded chains propagating in the [01] direction through alternating centrosymmetric R 2 2(8) rings with pairwise N-Hâ¯O inter-actions and centrosymmetric R 2 2(8) rings with pairwise N-Hâ¯N inter-actions. The crystal chosen for data collection was found to be a non-merohedral twin (180° rotation about [001]) in a 0.446â (4):0.554â (6) domain ratio.
RESUMO
The title compound, C12H15NO3, crystallizes with Z' = 2 in space group Pca21 with the two independent mol-ecules having almost the same conformation, differing mostly at the end of the butanamide chain. A local inversion center near 1/8, 3/4, z relates the two mol-ecules, as is common for structures in this space group with Z' = 2. The mol-ecule crystallizes as the keto tautomer, and the ß-diketone moieties are twisted out of planarity, with O-Câ¯C-O pseudo torsion angles of -74.4â (5) and -83.9â (5)°. The N-H group of each independent mol-ecule donates an inter-molecular hydrogen bond to an amide carbonyl oxygen atom by positive or negative translations along the b axis, thus forming anti-parallel chains propagating in the [010] direction.
RESUMO
The study of the oxidation of various proteins necessitates scrutiny of the amino acid sequence. Since me-thio-nine (Met) and tyrosine (Tyr) are easily oxidized, peptides that contain these amino acids are frequently studied using a variety of oxidation methods, including, but not limited to, pulse radiolysis, electrochemical oxidation, and laser flash photolysis. To date, the oxidation of the Met-Tyr dipeptide is not fully understood. Several investigators have proposed a mechanism of intra-molecular electron transfer between the sulfide radical of Met and the Tyr residue. Our elucidation of the structure and absolute configuration of l-Met-l-Tyr monohydrate, C14H20N2O4S·H2O (systematic name: (2S)-2-{[(2S)-2-amino-4-methyl-sulfanyl-butano-yl]amino}-3-(4-hy-droxy-phen-yl)propanoic acid monohydrate) is presented herein and provides information about the zwitterionic nature of the dipeptide. We suspect that the zwitterionic state of the dipeptide and its inter-action within the solvent medium may play a major role in the oxidation of the dipeptide. In the crystal, all the potential donor atoms inter-act via strong N-Hâ¯O, C-Hâ¯O, O-Hâ¯S, and O-Hâ¯O hydrogen bonds.
RESUMO
In the title compound, racemic bucetin [systematic name: N-(4-eth-oxy-phen-yl)-3-hydroxy-butanamide], C12H17NO3, the mol-ecule is in an extended conformation as illustrated by the C-O-C-C torsion angle [170.14â (15)°] in the eth-oxy group and the subsequent C-N-C-C [-177.24â (16)°], N-C-C-C [170.08â (15)°] and C-C-C-C [171.41â (15)°] torsion angles in the butanamide chain. In the crystal, the O-H group donates an inter-molecular O-Hâ¯O hydrogen bond to the amide carbonyl oxygen atom and also accepts an inter-molecular N-Hâ¯O hydrogen bond from an adjacent N-H group. The former forms 12-membered dimeric rings about inversion centers, and the latter form chains in the [001] direction. The overall hydrogen-bonded network is two-dimensional, with no propagation in the [100] direction.
RESUMO
The title compound, C9H10N2O4, crystallizes with a disordered nitro group in twinned crystals. Both the meth-oxy group and the acetamide groups are nearly coplanar with the phenyl ring, and the C-N-C-O torsion angle [0.2â (4)°] is also insignificantly different from zero. Overall, the 12-atom meth-oxy-phenyl-acetamide group is nearly planar, with an r.m.s. deviation of 0.042â Å. The nitro group is twisted out of this plane by about 30°, disordered into two orientations with opposite senses of twist. In the crystal, the N-H group donates a hydrogen bond to a nitro oxygen atom, generating chains propagating in the [101] direction. The amide carbonyl oxygen atom is not involved in the hydrogen bonding.
RESUMO
A xenoestrogen and known endocrine disruptor, bisphenol A (BPA) binds the human estrogen-related receptor-gamma (ERRγ) with high affinity (Kd ≈ 5.5 nM). It is likely that BPA undergoes oxidative biotransformation by hypochlorite/hypochlorous acid ((-)OCl/HOCl) and peroxynitrite (PN) and the products formed in these reactions may serve as secondary estrogens and contribute to the toxicodynamics of BPA. Therefore, in the present study we have examined the formation of chlorinated and nitrated BPA in reactions of BPA with (-)OCl/HOCl and PN(+CO(2)) performed around the neutral pH. We have identified four major products in these reactions and they include 3-chloro-BPA (CBPA), 3,3'-dichloro-BPA (DCBPA), 3-nitro-BPA (NBPA) and 3,3'-dinitro-BPA (DNBPA). Towards understanding the toxicodynamics and estrogenic activity of BPA in biological systems, we have performed molecular docking of BPA, CBPA, DCBPA, DNBPA and NBPA onto the ERRγ using AutoDock 4.2 software and compared the binding energies with those of estradiol, the natural ligand. Based on the genetic algorithm, the three best conformations were selected and averaged for each ligand and a detailed analysis of molecular interactions based on free energies of binding (kcal/mol) was computed. The results indicate the following rank order of binding to ERRγ: BPA (-8.78 ± 0.06) > CBPA (-8.53 ± 0.41) > NBPA (-7.36 ± 0.74) > DCBPA (-5.24 ± 0.17) > DNBPA (-4.95 ± 0.78) > estradiol (-4.94 ± 1.04). The docking studies revealed that the OH group of one of the phenyl rings forms a hydrogen bond with Glu275/Arg316, while the OH group of other phenyl ring was bound to Asp346. These results suggest that both BPA and its putative chlorinated and nitrated metabolites have strong binding affinity compared to estradiol.
Assuntos
Compostos Benzidrílicos/química , Estrogênios não Esteroides/química , Fenóis/química , Receptores de Estrogênio/química , Domínio Catalítico , Linhagem Celular , Cloro/química , Estradiol/química , Humanos , Ácido Hipocloroso/química , Nitratos/química , Ácido Peroxinitroso/química , Ligação Proteica , Conformação ProteicaRESUMO
Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses.
Assuntos
Ácido Peroxinitroso/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Relação Dose-Resposta a Droga , Masculino , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Doadores de Óxido Nítrico/antagonistas & inibidores , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Oxidiazóis/farmacologia , Penicilamina/farmacologia , Ácido Peroxinitroso/antagonistas & inibidores , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacosRESUMO
The title compound, C(13)H(15)ClN(2)O(6), was synthesized by hypochlorous acid-mediated chlorination of N-acetyl-3-nitro-l-tyrosine ethyl ester. The OH group forms an intra-molecular O-Hâ¯O hydrogen bond to the nitro group and the N-H group forms an inter-molecular N-Hâ¯O hydrogen bonds to an amide O atom, linking the mol-ecules into chains along [100]. The crystal studied was a non-merohedral twin, with a 0.907â (4):0.093â (4) domain ratio.
RESUMO
The title compound, C8H8N2O4, differs in its degree of planarity from the 3-nitro isomer and also in its hydrogen-bonding pattern. Its NH group forms an intra-molecular hydrogen bond to a nitro oxygen atom, and its OH group forms an inter-molecular hydrogen bond to an amide oxygen atom, generating [10] chains in the crystal.
RESUMO
In the title compound, C9H10N2O4, the three substituents vary in the degree of lack of planarity with the central phenyl ring. The meth-oxy group is nearest to being coplanar, with a C-C-O-C torsion angle of 6.1â (5)°. The nitro group is less coplanar, with a 12.8â (5)° twist about the C-N bond and the acetamido group is considerably less coplanar with the central ring, having a 25.4â (5)° twist about the C-N bond to the ring. The NH group forms an intra-molecular N-Hâ¯O hydrogen bond to a nitro-group O atom.
RESUMO
3ß-Hydroxy-5,6-secocholestan-6-al (cholesterol secoaldehyde or ChSeco), an oxysterol known to be formed in ozone- and singlet oxygen-mediated oxidations of cholesterol, has been detected in the atherosclerotic plaque and in the brain of patients suffering from Alzheimer's disease and Lewy body dementia. Previously, we have shown that, in H9c2 cardiomyoblasts, ChSeco induces oxidative stress followed by apoptosis involving both intrinsic and extrinsic signaling pathways. In the present study, we investigated the nature of reactive oxygen species (ROS) and its associated redox signaling in H9c2 cells upon treatment with ChSeco. Both catalase and deferoxamine, which lowered intracellular ROS, were found to alleviate the ChSeco-induced cytotoxicity. ChSeco-treated H9c2 cells showed a significant decrease in the intracellular catalase activity, suggesting the involvement of H(2)O(2) in the associated cytotoxicity. Additionally, in ChSeco-exposed cells, there was a marked increase in lipid peroxidation and pre-treatment with SB 203580 (p38 MAPK inhibitor) and MEK1/2 inhibitor (ERK1/2 and JNK inhibitor) rendered protection against the cytotoxicity. An early increase in the expression of p-SAPK/JNK or delayed p38 MAPK did not alter ATF-2 but decreased c-Jun expression in these cells. Overall, these findings are consistent with MAPK signaling resulting from increased cellular H(2)O(2) in ChSeco-induced cytotoxicity in cardiomyoblasts.
Assuntos
Colestanonas/toxicidade , Peróxido de Hidrogênio/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mioblastos Cardíacos/efeitos dos fármacos , Secoesteroides/toxicidade , Apoptose , Linhagem Celular , Humanos , Imidazóis/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mioblastos Cardíacos/enzimologia , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse FisiológicoRESUMO
The cytotoxicity of dihydroartemisinin (DHART; an active metabolite of artemisinin or ART) was investigated using murine GT1-7 hypothalamic neurons. A decrease in neuronal cell viability was observed in DHART-treated cells typically after 6 h of incubation. When neuronal cells were exposed to DHART for 24 h, the value of IC50 was found to be 24 ± 3.2 µM (n = 6). Based on acridine orange/ethidium bromide (dual) staining and increases in oligonucleosomal fragmentation, the cell death at lower concentrations of DHART (≤ 20 µM) was suggestive of apoptotic in nature. On the other hand, at higher concentrations of DHART (≥ 50 µM), the cell death appeared to be predominantly necrotic. A potentiation of cytotoxic effects was seen in Fe(II)-containing medium whereas inclusion of deferoxamine (chelator of Fe) attenuated such effects. This would imply that the cleavage of the endoperoxide bridge of DHART by Fe(II) and the subsequent formation of O- and C-centered radical(s) are important determinants of the cytotoxicity that was observed. The activities of caspase-3/7, caspase-8 and caspase-9 were maximally seen at 12-h after exposure to DHART. Inhibitors of caspase-8 (C8I) but not caspase-9 (C9I) reduced the DHART-induced increase in caspase-3/7 activity. A relatively higher activity of caspase-8 to that of caspase-9 and the inhibition of caspsase-3/7 activity by C8I suggest that DHART induces caspase-8-mediated apoptosis involving the extrinsic pathway. Taken together, this study demonstrates that DHART and, possibly, other ART derivatives have considerable neurotoxic potential and facilitate our understanding of these agents.
Assuntos
Antimaláricos/toxicidade , Apoptose/efeitos dos fármacos , Artemisininas/toxicidade , Caspase 8/metabolismo , Hipotálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Inibidores de Caspase , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Hipotálamo/enzimologia , Hipotálamo/patologia , Camundongos , Necrose/induzido quimicamente , Neurônios/enzimologia , Neurônios/patologiaRESUMO
THE TITLE COMPOUND [SYSTEMATIC NAME: 2,2'-dinitro-4,4'-(propane-2,2-di-yl)diphenol], C(15)H(14)N(2)O(6), crystallizes with two mol-ecules in the asymmetric unit. Both have a trans conformation for their OH groups, and in each, the two aromatic rings are nearly orthogonal, with dihedral angles of 88.30â (3) and 89.62â (2)°. The nitro groups are nearly in the planes of their attached benzene rings, with C-C-N-O torsion angles in the range 1.21â (17)-4.06â (17)°, and they each accept an intra-molecular O-Hâ¯O hydrogen bond from their adjacent OH groups. One of the OH groups also forms a weak inter-molecular O-Hâ¯O hydrogen bond.
RESUMO
Cholesterol oxidation product, 3ß-hydroxy-5-oxo-5,6-secocholestan-6-al (cholesterol 5,6-secosterol, ChSeco or Atheronal-A), formed at inflammatory sites, has been shown to promote monocyte differentiation into macrophages and cause elevated expression of macrophage scavenger receptors. Since inflammation is a key event at all stages of atherosclerotic plaque formation, the pro-inflammatory actions of ChSeco in human THP-1 monocytes and mouse J774 macrophages were investigated in the present study by employing ELISA, qRT-PCR, and functional assays. An increase in the secretion of interleukin-8 and platelet-derived growth factor (PDGF) isoform AA and, to a limited extent, PDGF isoform BB was observed into the culture medium of THP-1 monocytes exposed to ChSeco. However, no changes were seen in the secretion of tumor necrosis factor-alpha. In J774 macrophages treated with ChSeco, there was an upregulation of gene expression of several pro-inflammatory cytokines and their receptors. Concomitantly, there was down-regulation of gene expression of interleukin-1ß, interleukin-10, and lymphotoxin-beta. An increase in the release of interleukin-18 and chemokine (C-C motif) ligand-20 from J774 macrophages (which corroborated well with their gene expression profiles) and increased binding of THP-1 monocytes to ChSeco-exposed human aortic endothelial cells were observed. The results of the present study, for the first time, demonstrate the pro-inflammatory action of ChSeco and suggest the underlying pro-atherogenic mechanisms. These could be mediated through enhanced monocyte recruitment into the sub-endothelial space and subsequent proliferation of smooth muscle cells under the influence of monocyte-derived PDGF.
Assuntos
MonócitosRESUMO
In the present study, HFD/STZ-mediated type 2 diabetic rodent model was used to comparatively evaluate coconut oil (CO) and thermally oxidized CO (TCO) as fat sources for the development of NAFLD. Female Wistar rats (six in each group; average bwt 200 g) fed HFD containing either CO or TCO for 2 months along with an intraperitoneal injection of streptozotocin (30 mg/kg bwt) at the end of 1-month feeding were found to develop fatty liver and subsequent inflammatory changes when compared to the normal laboratory diet-fed animals over 2-month period. Dyslipidemia as well as enhanced activities of serum hepatic marker enzymes (e.g., AST, ALT, and ALP) were prominent in TCO-fed animals. Further, HFD-fed animals showed alterations in their hepatic redox equilibrium. Hepatic GSH and antioxidant enzyme activities that form the part of a protective mechanism against oxidative/carbonyl stress were found to be increased in HFD-fed rats. Supporting this, CO- and TCO-containing-HFD-fed animals had enhanced lipid peroxidation (increased TBARs). Thus, fatty liver with heightened antioxidant defense, lipid peroxidation, and inflammation indicate hepatosteatosis. Histological details of the hepatic tissues corroborated sufficiently with these observations and showed an increased incidence of macrovesicles, inflammation, and hepatocyte ballooning in the TCO-fed rats than in CO-fed animals. Further, in support of this proposition, hydroxyproline, an index of collagen formation, was found to be significantly increased in TCO-fed rats than in the CO-fed group. Overall, the study shows that the formulation of HFD incorporated with TCO as a fat source, combined with STZ injection, is an efficient dietary model for developing hepatosteatosis with fibrotic stage in rats within 2 months. Administration of this modified diet for a more extended period may be a good model for cirrhotic and hepatocellular carcinoma studies, which need to be further assessed.