Aryl Hydrocarbon Hydroxylase Research Articles

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene-induced experimental lung cancer.

Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P-induced lung cancer-bearing animals displayed cachexia-like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma-glutamyl transpeptidase, 5'-nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P-induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P-induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P-induced animals downregulated phosphatidylinositol 3-kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase-3, and p53 with a parallel increase in antiapoptotic Bcl-2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P-induced experimental lung tumorigenesis.

Evaluation of toxic effects of petroleum hydrocarbon on Mytilus coruscus under different salinity based on an integrated biomarker response index

ABSTRACT An oxidative stress experiment of crude oil in Pinghu on Mytilus coruscus under different salinities (10, 15 and 20) for 15 days was carried out in this study. Oxidative stress of oil pollutants in digestive glands was measured by several typical biomarkers, the levels of ethoxyresourufin-O-deethylase (EROD) activities and aryl hydrocarbon hydroxylase (AHH) activities, CYP1A1mRNA content and DNA damage degree. The integrated biomarker response index (IBR) was introduced in for the quantitative evaluation of the responses of M. cephalus to the toxic effects of crude oil in Pinghu under different salinities. The results showed that the different salinities of crude oil in Pinghu can induce toxic effects on the digestive glands of M. coruscus to different extents, and the order of the degrees of toxicity, which were higher than those of the control groups, was 20 salinity > 15 salinity > 10 salinity. .

Use of computational toxicology tools to predict in vivo endpoints associated with Mode of Action and the endocannabinoid system: A case study with chlorpyrifos, chlorpyrifos-oxon and Δ9Tetrahydrocannabinol

Currently, there is a lack of knowledge about the effects of co-exposures of cannabis, contaminated with pesticides like chlorpyrifos (CPF) and the toxic metabolite CPF-oxon (CPFO). CPF/CPFO residues, and Δ9Tetrahydrocannabinol (Δ9THC), the main component in cannabis, are known to disrupt the endocannabinoid system (eCBS) resulting in neurodevelopmental defects. Although there are in vivo data characterizing CPF/CPFO and Δ9THC, there are mechanistic data gaps and deficiencies. In this study, an investigation of open access CompTox tools and ToxCast/Tox21 data was performed to determine targets relating to the modes of action (MOA) for these compounds and, given the available biological targets, predict points of departure (POD). The main findings were as follows: 1) In vivo PODs for each chemical were from open literature, 2) Concordance between ToxCast/Tox21 assay targets and known targets in the metabolic and eCBS pathways was evaluated, 3) Human Equivalent Administered Dose (EADHuman) PODs showed the High throughput toxicokinetic (HTTK) 3 compartment model (3COMP) was more predictive of in vivo PODs than the PBTK model for CPF, CPFO and Δ9THC, 4) Age-adjusted 3COMP HTTK-Pop EADHuman, with CPF and CPFO ToxCast/Tox21 AC50 values as inputs were predictive for ages 0–4 when but not Δ9THC compared to in vivo PODs. 5) Age-related refinements for CPF/CPFO were primarily from ToxCast/Tox21 active hit-calls for nuclear receptors, CYP2B6 and AChE inhibition (CPFO only) associated with the metabolic pathway. Only one assay target (arylhydrocarbon hydroxylase receptor) was common between CPF/CPFO and Δ9THC. While computational refinements may select some sensitive events involved in the metabolic pathways; this is highly dependent on the cytotoxicity limits, availability of metabolic activity in the ToxCast/Tox21 assays and reliability of assay performance. Some uncertainties and data gaps for Δ9THC might be addressed with assays specific to the eCBS. For CPF, assays with appropriate metabolic activation could better represent the toxic pathway.

Chemoprotective effect of atorvastatin against benzo(a)pyrene-induced lung cancer via the inhibition of oxidative stress and inflammatory parameters.

BackgroundLung cancer affects approximately 9% of women and 17% of men worldwide, and has a mortality rate of 17%. Previously published studies have suggested that oxidative stress expansion can lead to lung cancer. The aim of the current study was to analyze the possible inhibitory pathway of atorvastatin against lung cancer cells in an in vivo model.MethodsThe cytotoxic effects of atorvastatin on lung cancer cell lines H460 and A549 were analyzed, as well as cell cycle arrest and cell morphology. Benzo(a)pyrene (BaP) was used for the induction of lung cancer in experimental rats, and atorvastatin (5, 10, and 20 mg/kg body weight) was used for treatment in a dose-dependent manner. Body weight and lung tumors were calculated at regular intervals. Antioxidants, pro-inflammatory cytokines, phase I and II antioxidant enzymes, polyamine enzymes, and apoptosis markers were determined at end of the experimental study.ResultsCell cycle arrest occurred at the G2/M phase after atorvastatin treatment. Atorvastatin increased cytochrome C expression and caspase activity in a dose-dependent manner, and increased the activity of antioxidative enzymes, such as GPx, SOD, GST, reduced glutathione, and catalase, and reduced the level of nitrate and LPO. It also altered the xanthine oxidase (XO), Lactic Acid Dehydrogenase (LDH), quinone reductase (QR), UDP-glucuronosyltransferase (UDP-GT), adenosine deaminase (ADA), Aryl hydrocarbon hydroxylase (AHH), 5'-nucleotidase, cytochrome P450, cytochrome B5 and NADPH cytochrome C reductase levels. Atorvastatin was found to modulate polyamine enzyme levels, such as histamine, spermine, spermidine, and putrescine, and significantly (P<0.001) reduced the pro-inflammatory cytokine levels, such as tumor necrosis factor-α. Interleukin (IL)-6 and interleukin-1β (IL-1β) increased caspase-3 and caspase-9 levels in a dose-dependent manner.ConclusionsOur findings indicate that atorvastatin can inhibit lung cancer through apoptosis.

Anticancer Effect of Troxerutin in Human Non-Small-Cell Lung Cancer Cell A549 and Inhibition of Tumor Formation in BALB/c Nude Mice.

This study is intended to explore the anticancer, antiproliferative, and chemopreventive action of troxerutin (TX) in human non-small-cell lung cancer cell (A549) using BALB/c nude mice. 2 × 106 A549 cells were subcutaneously injected into mice, along with 10 μM and 20 μM/kg body weight of TX orally for 19 days. On the last day, tumor weight and volume were assessed. Stress marker enzymes such as Aryl hydrocarbon hydroxylase (AHH), lactate dehydrogenase (LDH), 5'Nucleotidase (5'ND), and γ-glutamyltranspeptidase (γ-GT) were estimated in the lung tissues. Cytotoxicity of TX was assessed using MTT assay. Expression of carcinoembryonic antigen (CEA) and inflammatory cytokines were also analyzed. Histopathological examination of tissue sections and immunohistochemical examination of proliferating cell nuclear antigen (PCNA) were also performed. mRNA expression of p53, p21, cyclin D1, P13k, Akt, and mTOR were analyzed using RT-PCR. TX administered orally in a dose-dependent manner markedly reverted the level of stress marker enzymes to a significant extent. TX also exhibited significant protection against lung cancer cells, as evidenced by cytotoxicity assay and histopathological studies. It was also found to reduce the expression of PCNA, cyclin D1, P13k, Akt, and mTOR, but increase the expression of p53 and p21. TX has also been shown to reduce cancer cell inflammation, as was evidenced by reduced expression of inflammatory cytokines. Thus TX could be used as an effective chemopreventive and anticancer agent in treating cancer.

Management of early lung tumorigenesis by corilagin via modulation of proliferating cell nuclear antigen and apoptotic pathway

Background: Corilagin is vastly found in plants and incorporated in countless traditional medicinal systems to treat various ailments including cancer disease. However, till now, no scientific study has been done to validate its efficiency with appropriate experimental evidence. Resulting, this study examined the ameliorative effects of corilagin in benzo(a)pyrene (B[a] P)-induced lung cancer in vivo. Methods: Experimentally, the B(a)P (50 mg/kg body weight [b.wt.]) was administered orally to initiate lung cancer in mice, and the supplementation of prophylactic and therapeutic treatment by corilagin (30 mg/kg b.wt.) was observed for changes in b.wt. and lung weight, tumor incidence, oxidative stress marker (lipid peroxidation), tumor markers (carcinoembryonic antigen, neuron-specific enolase, aryl hydrocarbon hydroxylase, lactate dehydrogenase, γ-glutamyl transpeptidase, 5′-nucleotidase, alpha-keto dehydrogenase, citric acid cycle enzymes isocitrate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase), histological and immunohistochemical analysis (proliferating cell nuclear antigen), and apoptotic mRNA gene expression (Bax, Bcl-2, caspase-3, caspase-9, and cytochrome-c). Results: B(a)P-induced animals exhibited unusual changes in b.wt. and lung weight, tumor incidence, oxidative stress marker, enzymatic antioxidants, tumor markers, histological lung tissue damage, number of proliferating cell nuclear antigen, and apoptotic mRNA gene expression. On prophylactic and therapeutic treatment of corilagin, the animals showed reinstatement of all the above alterations to the near normal. Conclusion: These findings of all the analyzed data demonstrate that the B(a)P-induced animals of pre- and post-treated with corilagin may prevent initiation of lung cancer, hence establishing its chemopreventive effect against lung tumorigenesis.

Bioaccumulation and oxidative damage of polycyclic aromatic hydrocarbon mixtures in Manila clam Ruditapes philippinarum.

The aim of this study was to investigate the bioaccumulation and oxidative damage of Manila clam, Ruditapes philippinarum, exposed to four selected mixtures of polycyclic aromatic hydrocarbons (PAHs; benzo (a) pyrene (BaP), benzo (a) anthracene (BaA), benzo (b) fluoranthene (BbF), and chrysene (Chr) in equal proportion. For this purpose, clams were exposed to PAHs (BaP:BbF:BaA:Chr=1:1:1:1) at different concentrations (0.05, 0.5, and 5μg/L) for 21 days, followed by a 15-day depuration period. All four PAHs accumulated in the gill, digestive gland, adductor muscle, and soft tissue of Manila clams, and all PAH treatment groups showed clear time and dose dependence. The decreasing order of bioaccumulation for the four PAHs in the exposure experiment was Chr>BaA>BaP>BbF. Moreover, the order of PAH bioaccumulation for the four tissues during the whole experiment was digestive gland>gill>soft tissues>adductor muscles. Although the initial concentrations of the four PAHs were the same, the final accumulated contents were different. Therefore, we also determined the detoxification processes of the four PAH mixtures in gills and digestive glands. The bioaccumulation of Chr was higher than the other three PAHs, probably because clams have a lower metabolic capacity for Chr than for BaP, BbF, and BaA. Exposure to PAH mixtures can result in oxidative damage, as indicated by the fact that DNA strand breaks, lipid peroxidation (LPO), and protein carbonyl (PC) were induced significantly (P<0.05), except in the low-dose groups of PAHs, and different trends were detected with time of exposure. According to the correlation analysis, aryl hydrocarbon hydroxylase, glutathione s-transferase, superoxide dismutase, DNA strand break, PC, and LPO in both the gill and digestive gland are potential early indicators of PAH mixtures. We investigated the accumulation rules of R. philippinarum exposed to the selected PAHs and screened the potential biomarkers. The results of our study provide important scientific information for the purpose of monitoring marine pollution.

Synthesis, Characterization, Computation of Global Reactivity Descriptors and Antiproliferative Activity of N-(4-nitrophenyl)Acrylamide

In this article N-(4-nitrophenyl)acrylamide has been synthesized and characterized both experimentally and theoretically. The synthesized monomer was characterized experimentally by Fourier Transform Infrared, Nuclear Magnetic Resonance spectroscopic techniques and theoretically by Density Functional Theory and Time-Dependent Density Functional Theory methods at Coulomb Attenuated Method level. To investigate the natural toxicity and reactivity of the title molecule optimized at the Density Functional Theory/Coulomb Attenuated Method- Becke three-parameter Lee-Yang-Parr level, the chemical reactivity descriptors were calculated based on the rotational barriers. Using the Parr formula, the interaction between N-(4-nitrophenyl)acrylamide molecule and nucleic acid bases (adenine, thymine, cytosine, uracil and guanine) phenylalanine and histidine an Aryl Hydrocarbon hydroxylase receptors were investigated. Charge transfer that is important in the formation of chemically bonded adducts causing cancer has been calculated quantitatively. In addition, in vitro cytotoxicity of N-(4-nitrophenyl)acrylamide on HeLa cell lines has been studied. It has been found that the half maximal inhibitory concentration value of N-(4-nitrophenyl)acrylamide is 1 mM in HeLa cells. Our results show that N-(4-nitrophenyl)acrylamide, an acrylamide-based molecule that is accepted as toxic by the World Health Organization, has low toxicity on cancer cells by experimental study and, in theory, it has low toxicity according to calculations of reactivity descriptors, therefore can be used for biomedical research.

Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic acid as antioxidants.

Tramadol is an analgesic used to treat moderate to severe pain caused by cancer, osteoarthritis, and other musculoskeletal diseases. Cytochrome P450 system metabolizes tramadol and induces oxidative stress in different organs. Therefore, the present study aims at investigating the changes in the activities and the protein expressions of CYPs isozymes (2E1, 3A4, 2B1/2), antioxidants status, free radicals levels after pretreatment of rats with Curcumin and/or Gallic as single- and/or repeated-doses before administration of tramadol. In repeated-dose treatments of rats with tramadol, the activities of cytochrome P450, cytochrome b5, and NADPH-cytochrome-c-reductase, and the antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the liver and the kidney of rats. Interestingly, such changes caused by tramadol restored to their normal levels after pretreatment of rats with either Curcumin and/or Gallic acid. On the other hand, repeated-dose treatment of rats with tramadol increased the activities of both dimethylnitrosamine N-demethylase I (DMN-dI), and aryl hydrocarbon hydroxylase (AHH) compared to the control group. However, pretreatment of rats with Curcumin and/or Gallic acid prior to administration of tramadol restored the inhibited DMN-dI activity and its protein expression (CYP 2E1) to their normal levels. On the other hand, tramadol inhibited the activity of ethoxycoumarin O-deethylase (ECOD) and suppressed its protein marker expression (CYP2B1/2), whereas Curcumin, Gallic acid and/or their mixture restored such changes to their normal levels. In conclusion, Curcumin and/or Gallic acid alleviated the adverse effects caused by tramadol. In addition, patients should be advice to take Curcumin and/or Gallic acid prior to tramadol treatment to alleviate the hepatic and renal toxicities caused by tramadol.

PIPERINE: A NATURAL BIOENHANCER

Herbal sources have been explored recently at very high frequency owing to their lower risk benefit ratio as compared to the modern allopathic medicine systems. Herbal bioenhancer is an agent of herbal origin or any phytomolecule, which is capable of enhancing bioavailability and bioefficacy of a particular drug or nutrient with which it is combined, without any typical pharmacological activity of its own at the dose used. The active compound of both Long pepper ( Piper longum ) and Black pepper ( Piper nigrum ) is piperine (1-piperoyl piperidine), which is responsible for bioenhancing effect. Piperine enhances absorption from gastrointestinal tract by various mechanisms and reduces gut metabolism of drugs. Piperine modulates membrane dynamics and lipid environment and increases permeability at site of absorption. Thus, piperine acts as absorption enhancer and is a potent inhibitor of drug metabolism as it inhibits various metabolizing enzymes like human p-glycoproteins, CYP3A4, UDP-glucose dehydrogenase (UDP-GDH), aryl hydrocarbon hydroxylase (AAH) and UDP-glucuronyl transferase. The current review also describes the mechanism of action of piperine and bioavailability action of piperine on drugs and nutrients.

Toxic effects upon exposure to polycyclic aromatic hydrocarbon (chrysene) in scallop Chlamys farreri during the reproduction period.

This study aims to investigate potential toxic effects of chrysene (CHR) on mature scallop Chlamys farreri during the reproduction period, using indicators of antioxidant defences and oxidative stress. Scallops were exposed to 0.2, 0.8 and 3.2μg/L waterborne CHR for 21 days, at day 10 scallops were induced to spawn. At days 1, 3, 6, 10, 11, 15 and 21, aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin-O-deethylase (EROD), glutathione-s-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), lipid peroxidation (LPO), protein carbonyl (PC) and DNA strand breaks in digestive glands were examined by separately analysing male and female scallops. During the pre-spawn period, Levels of enzymatic activities and oxidative stress were all induced by the exposure to CHR for females and males. GST activity presented a good time- and dose-dependent relationship only in males, and GSH content showed a dose-dependent manner in both sexes. During the post-spawn period, different trends were observed, while PC contents maintained growth in time- and dose-dependent manner. Overall, males were more sensitive than females to CHR exposure in enzyme activities, and correspondingly, females suffered from more serious oxidative damages. Both GSH and PC contents seemed to be potential biomarkers for PAH exposure. These results will offer the information on toxicity of CHR in this species, and ensure the influence of gender and reproductive status on PAH detoxification metabolism.

Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats.

Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along with its corresponding enzyme marker ECOD activity. It is concluded that changes in the expression and activity of phase I drug-metabolising enzymes could change the normal metabolic pathways and might enhance the deleterious effects of exogenous as well as endogenous compounds.

QSAR Studies of the Dioxins and Interaction of OCDD with Calix(4) Arene Using DFT

Quantum chemical calculations, based on Density Functional Theory (DFT) method, were performed on Calix[4]arene and Polychlorinated Dibenzo-p-dioxins (PCDDs) in gas and liquid phases for comparison purposes. The simulation results show the 1,2,3,4, 6,7,8,9-octachlorodibenzo-p-dioxin (OCDD) is quite a reactive dioxin. This paper attempts to examine the possibility of dioxin adsorption by Calix[n]arene from the environment. The interaction between Calix[4]arene and OCDD is investigated using the B3LYP method and LANL2DZ level of DFT in both gas and liquid phases. The results show that the OCDD acts as an electron acceptor and Calix[4]arene acts as an electron donor. A linear model of Quantitative Structure Activity Relationship (QSAR) has been approximated to calculate the binding affinity (BA) and induction potencies of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD). According to this model, the calculated BA of the dioxins were found to be close to their experimental values.

Biomarker responses in the bivalve Chlamys farreri to the water-soluble fraction of crude oil

To investigate the effect of the water soluble fraction of crude oil (WSF) on marine bivalves, the scallop Chlamys farreri was exposed to three WSF concentrations (0.18 mg/L, 0.32 mg/L, and 0.51 mg/L, respectively) in seawater. Petroleum hydrocarbon contents in scallops and a suite of enzymes [7-Ethoxyresorufin-O-deethylase (EROD), aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase (GST), and glutathione peroxidase (GPx)] in gills and digestive glands were monitored over 10 days. The results revealed that WSF affected the activity of the four enzymes in the gills and digestive glands. EROD activity in the gills was significantly induced in most individuals of the three test groups, while in the digestive gland it was significantly induced in the low-concentration group within 4 days but was inhibited in the middle- and high-concentration groups on days 1, 4, and 10. AHH activity in the gills of all treatment groups was significantly induced on day 1. In the digestive gland, AHH activity was induced in most individuals from the treatment groups. In all treatment groups, GST activity was significantly inhibited from days 2 to 10 in the gills and was induced after day 4 in the digestive gland. GPx activity in the gills was significantly inhibited throughout the exposure period in all treatment groups. There was no overall significant difference in GPx activity in the digestive gland between the control and treatment groups. Our results also revealed that petroleum hydrocarbon concentrations in the tissues increased linearly with exposure time. EROD activity in the digestive gland and GST and GPx activity in the gill tissue were negatively correlated with petroleum hydrocarbon body burden. These enzymes play important roles in detoxification and can act as potential biomarkers for monitoring petroleum hydrocarbon contaminants in the marine environment.

Curcumin and resveratrol in combination modulate drug-metabolizing enzymes as well as antioxidant indices during lung carcinogenesis in mice.

This study investigated combined chemopreventive potential of curcumin and resveratrol during benzo(a)pyrene (BP)-induced lung carcinogenesis in mice. The mice were segregated into five groups that included normal control, BP-treated, BP + curcumin-treated, BP + resveratrol-treated, and BP + curcumin + resveratrol-treated groups. A statistically significant increase in the levels of lipid peroxidation (LPO) was observed in the lungs of mice after 22 weeks of single dose of benzo(a)pyrene. Further, BP treatment also resulted in a significant increase in the enzyme activities of aryl hydrocarbon hydroxylase as well as drug-metabolizing enzymes, namely cytocrome P450 and cytochrome b5. On the other hand, reduced glutathione (GSH) levels, the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione-S-transferase (GST) were found to be significantly decreased following BP treatment. Supplementation with curcumin and resveratrol to BP-treated mice significantly decreased the LPO levels, GSH levels, and enzyme activities of drug-metabolizing enzymes. Further, treatment of curcumin and resveratrol to BP-treated mice significantly elevated the activities of SOD, GR, and GST. Histoarchitectural studies showed well-differentiated signs of lung carcinogenesis following BP administration to mice. However, combined treatment with curcumin and resveratrol resulted in a noticeable improvement in the lung histoarchitecture. This study, therefore, concludes that curcumin and resveratrol when supplemented in combination regulate drug-metabolizing enzymes as well as antioxidant enzymes during lung carcinogenesis in mice.

The detoxification process, bioaccumulation and damage effect in juvenile white shrimp Litopenaeus vannamei exposed to chrysene

This study aimed to evaluate the effect of chrysene (CHR) on detoxification enzymes, bioaccumulation and effect of CHR on biomolecule damage in different organs of the juvenile white shrimp Litopenaeus vannamei. In this study, juvenile white shrimp L. vannamei were exposed to CHR for 21 days at four different concentrations as 0, 0.3, 2.1 and 14.7μg/L. Results showed that CHR bioaccumulation increased rapidly at first then reached a plateau. The activities of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH), glutathione-S-transferase (GST), sulfotransferase (SULT) and uridinediphosphate glucuronyltransferase (UGT) were induced and then became stable gradually. Moreover, 2.1 and 14.7μg/L CHR treatments increased activity of superoxide dismutase (SOD) in gills and hepatopancreas, while total antioxidant capacity (T-AOC) and GSH/GSSG were suppressed after CHR exposure. Additionally, lipid peroxidation (LPO) levels, protein carbonyl (PC) contents and DNA damage were induced throughout the exposure period, and different trends were detected with time of exposure. Overall, these novel findings of CHR bioaccumulation and resulted toxicity demonstrate that CHR could affect the physical status of L. vannamei. This study will form a solid basis for a realistic extrapolation scientific data for aquaculture water monitoring and food security.

Protective role of Solanum trilobatum (Solanaeace) against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

ObjectiveTo investigate the protective effect of leaf extract of Solanum trilobatum (ELEST) against benzo(a)pyrene (BP) induced lung carcinogenesis. MethodsExperiment was designed with the treatment regimen of ELEST [200mg/kg body weight dissolved in dimethyl sulphoxide(DMSO)] for 4weeks before (pre-initiation) and from 12th week after B(a)P (50mg/kg body weight) induced lung carcinoma(post-initation). ResultsAdministration of BP (50mg/kg body weight) resulted in increased lipid peroxidation (LPO) and marker enzymes, such as arylhydrocarbon hydroxylase (AHH), gamma-glutamyl transpeptidase (γGT), 5′-nucleotidase (5′ND) and lactate dehydrogenase (LDH) along with decrease in the levels of tissue antioxidants, like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C in mice. Significantly, ELEST modulated these alterations suggest the efficacy of ELEST in the chemotherapeutics of lung cancer. The histopathological studies also evidenced the protective efficiency of the extract against lung carcinogenesis. Further, significant increase in the levels of Cytochrome P450, Cytochrome b5, NADPH Cyt c reductase and decrease in UDP-glucuronyl transferase and quinone reductase was observed in microsomal fraction of lung and liver of BP-induced mice, whereas the treatment with ELEST resulted in reversal of modulations observed in the activities of detoxification enzymes. ConclusionsCollectively, the present observations indicate that the treatment with ELEST exhibited protective and antioxidant effect against BP-induced lung carcinogenesis.

Metabolites analysis, metabolic enzyme activities and bioaccumulation in the clam Ruditapes philippinarum exposed to benzo[a]pyrene

A study was performed on clams (Ruditapes philippinarum) exposed to 0.03, 0.3 and 3μg/L benzo[a]pyrene (B[a]P) for 21 days. B[a]P metabolite contents, activities of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH), dihydrodiol dehydrogenase (DD), glutathione-S-transferase (GST), sulfotransferase (SULT) and uridinediphosphate glucuronyltransferase (UGT) and B[a]P bioaccumulation were assayed in gills and digestive glands. Results showed that the order of B[a]P phase I metabolite contents was 9-hydroxy-B[a]P>B[a]P-1,6-dione>B[a]P-7,8-dihydrodiol, and the concentration of B[a]P-7,8-dihydrodiol sulfate conjugates was higher than that of B[a]P-7,8-dihydrodiol glucuronide conjugates. B[a]P accumulation and the activities of AHH, EROD, EH, DD, SULT and UGT increased first and then reached equilibrium. GST activity was induced first and then depressed. The concentration of B[a]P was far higher than that of its metabolites. Besides, there were no significant differences between enzyme activities in gills and those in digestive glands. These results provided information on B[a]P metabolic mechanism in bivalve and scientific data for pollution monitoring and food security.

The Toxicological Effects of Halogenated Naphthalenes: A Review of Aryl Hydrocarbon Receptor-Mediated (Dioxin-like) Relative Potency Factors

There is no doubt that chloronaphthalenes (PCNs) and their brominated counterparts (PBNs) are dioxin-like compounds, but there is less evidence for mixed bromo/chloronaphthalenes (PXNs). In this article we review information relating to the dioxin-like potency of PCNs and PBNs obtained in vivo, in vitro, and in silico. The aim was to help and improve the quality of data when assessing the contribution of these compounds in the risk analysis of dioxin-like contaminants in foods and other sample types. In vivo and in vitro studies have demonstrated that PCN/PBN congeners are inducers of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase, and luciferase enzymes that are features specifically indicative of planar diaromatic halogenated hydrocarbons such as dioxin and dioxin-like compounds. PCNs in the environment are of multisource origin. The limited data on PBNs in the environment suggest that these also appear to originate from different sources. The toxicological data on these compounds is even scarcer, most of it directed toward explaining the exposure risk from accidental contamination of feed with the commercial PBN containing product, Firemaster BP-6. The occurrence of PBNs and PXNs is possible as ultra-trace environmental and food-chain contaminants produced at least from combustion processes at unknown concentrations. Available toxicological and environmental data enable a focus on PCNs as dioxin analogues to an extent that specific local or regional environmental influences could result in a risk to human health. There is the possibility that they may act synergistically with the better-known classic dioxin and other dioxin-like compounds. PBNs and PXNs are much less studied than the dioxins, but are known to be products of anthropogenic processes that contaminate the environment. A continuously increasing use of bromine for manufacture of brominated flame retardants over the past three decades is anticipated as a stream of “brominated” wastes, that when degraded (combusted), will release PBNs and PXNs. This calls for advanced analytical methods and greater interest toxicologically to understand and control pollution and exposure by PBNs and PXNs. Particular congeners of bromonaphthalene in single studies were found to be much more toxic than their chlorinated counterparts. In addition, brominated/chlorinated naphthalenes also seem to be more potent toxicants than PCNs.About 20% of PCN congeners exhibit a dioxin-like toxicity with relative potencies varying between around 0.003 and 0.000001, but additional and more rigorous data are needed to confirm these figures. Recent food surveys have estimated a small but relevant human exposure to these compounds in foods, giving an additional source of dioxin-like toxicity to those compounds already covered by the World Health Organization–Toxic Equivalency Factors (TEFs) scheme. Given the additivity of response postulated for other dioxin-like compounds, it would seem unwise to ignore this additional contribution. Few data available showed that PBN congeners also exhibit a dioxin-like toxicity and are even more potent than PCN congeners, but the relative potency values were not derived for them until now. There are no toxicological data available for PXNs.

Association of CYPA1 gene polymorphism with plasma nitric oxide levels in COPD

Background Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation, abnormal permanent distal air-space enlargement and emphysema in the lungs. Increased oxidative burden in COPD is because of both directly a result of smoking and indirectly by the release of increasing amount of ROS from airways leukocytes. The CYP1A1 gene modifies the phase I enzyme aryl hydrocarbon hydroxylase (AHH) belonging to the cytochrome P450 system that plays a major role in the metabolism of exogenous toxins generated by cigarette smoke [1]. The aim of the present study is to assess the role of CYP1A1 gene polymorphism and to measure the plasma nitric oxide levels in the etiology of COPD in South Indian Population from Andhra Pradesh.