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1.
Nat Prod Res ; 37(10): 1698-1701, 2023 May.
Article in English | MEDLINE | ID: mdl-35904413

ABSTRACT

Myroxylon pereirae resin (MP; balsam of Peru) is a botanical balsam which is derived from a tree known as Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms, balsamum. This natural substance has a long history of medicinal use (antiseptic and for wound healing) but surprisingly there is a lack of toxicological data. The medicinal application of Peru balsam has been documented throughout a period of at least 30 years, however, due to the high risk of sensitisation and other treatment options available in the proposed indication, the medicinal use of MP in EU today is limited. The aim of this article is deriving Permitted Daily Exposure (PDE) values for MP for regulatory purposes using various toxicological strategies due to the problems with toxicological data. The results described in this article fills a gap in the literature on toxicological aspects of MP for the first time.


Subject(s)
Balsams , Myroxylon , Resins, Plant/toxicity
2.
Regul Toxicol Pharmacol ; 127: 105076, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34742868

ABSTRACT

Myrrh is a flavoring agent and food additive. Here, we performed a subchronic toxicity study of Myrrh in male and female F344 rats by feeding at 5,000, 15,000 and 50,000 ppm for 90 days. No deaths or clinical signs were observed. Suppression of body weight gain was observed from the early phase of administration in both males and females in the 50,000 ppm group. Because there were no obvious changes in food intake in any of the Myrrh groups compared with the control group, suppression of body weight gain was considered an adverse effect of Myrrh. Hematology and serum biochemistry parameters with significant changes observed in the Myrrh groups were considered to have no toxicological significance. We observed a significant increase in relative kidney weight in male rats treated with 50,000 ppm Myrrh; this effect was considered to be related to the appearance of hyaline droplets in the epithelium of the proximal tubules histopathologically observed in this group. Immunohistochemical staining with anti-α2u-globulin antibodies suggested that these hyaline droplets were caused by factors other than α2u-globulin deposition. Thus, the no-observed-adverse-effect level of Myrrh was determined to be 15,000 ppm (males: 0.85 g/kg/day, females: 0.95 g/kg/day).


Subject(s)
Commiphora/toxicity , Flavoring Agents/toxicity , No-Observed-Adverse-Effect Level , Resins, Plant/toxicity , Animals , Dose-Response Relationship, Drug , Female , Hyalin/drug effects , Kidney/drug effects , Male , Organ Size/drug effects , Particle Size , Random Allocation , Rats , Rats, Inbred F344
3.
Molecules ; 26(13)2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34201875

ABSTRACT

The increased complexity due to the emergence and rapid spread of new viral infections prompts researchers to search for potential antiviral and protective agents for mucous membranes among various natural objects, for example, plant raw materials, their individual components, as well as the products of their chemical modification. Due to their structure, resin acids are valuable raw materials of natural origin to synthesize various bioactive substances. Therefore, the purpose of this study was to confirm the possibility of using resin acid derivatives for the drug design. As a result, we studied the cytotoxicity and biological activity of resin acid derivatives. It was shown that a slight decrease in the viral load in the supernatants was observed upon stimulation of cells (II) compared with the control. When using PASS-online modeling (Prediction of Activity Spectra for Substances), the prediction of the biological activity spectrum showed that compound (I) is capable of exhibiting antiviral activity against the influenza virus. The use of the SWISS-ADME webserver to reveal the drug-like properties of compounds did not directly indicate the presence of antiviral activity. These results indicate the potential of resin acid derivatives as a starting point for extensive research in the study of biological activity.


Subject(s)
Antiviral Agents/pharmacology , Influenza, Human/drug therapy , Orthomyxoviridae/drug effects , Resins, Plant/chemistry , Resins, Plant/pharmacology , A549 Cells , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacillus subtilis/drug effects , Candida tropicalis/drug effects , Cell Survival/drug effects , Drug Design , Escherichia coli/drug effects , Humans , Resins, Plant/toxicity , Structure-Activity Relationship
4.
Toxicol In Vitro ; 70: 105053, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33212168

ABSTRACT

Oakmoss and treemoss absolutes are the major natural extracts of concern as potential sources of skin sensitizers in cosmetics and personal care products (PCP). Two single constituents, atranol and chloroatranol, have been identified as primary culprits in both lichens, and industrial self-regulation has been proposed to limit their contents to less than 100 ppm. Nonetheless, evidence points to the presence of additional candidate skin sensitizers in these multicomponent extracts. These observations, along with a lack of data from non-animal alternative methods and the chemical variability of commercial absolutes, prompted further investigation of oakmoss absolute along with altranol-like compounds in these extracts. The major chemical constituents of a commercial sample were identified by two independent analytical techniques, GC-MS and HPLC-DAD-MS. The crude oakmoss extract and pure compounds were assayed with two in chemico methods (HTS-DCYA and DPRA) to gauge their chemical reactivity. Activation of inflammatory responses in vitro was also investigated by KeratinoSens™ and human cell line activation tests (h-CLAT). Based on weight of evidence, orcinol, ethyl orsellinate, and usnic acid were classified as candidate sensitizers, along with both atranols and oakmoss extract.


Subject(s)
Benzaldehydes/toxicity , Benzofurans/toxicity , Haptens/toxicity , Resins, Plant/toxicity , Resorcinols/toxicity , Terpenes/toxicity , Animal Testing Alternatives , Cell Line , Humans
5.
Exp Parasitol ; 195: 44-53, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30339984

ABSTRACT

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC50 = 3.90) and CUP (EC50 = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC50 = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis.


Subject(s)
Plant Extracts/therapeutic use , Resins, Plant/chemistry , Toxoplasmosis, Animal/drug therapy , Tracheophyta/chemistry , Acute Disease , Animals , Ascitic Fluid/parasitology , Brain/parasitology , Brain/pathology , Chronic Disease , Disease Models, Animal , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes/toxicity , Female , Liver/parasitology , Liver/pathology , Mice , Microscopy, Electron, Scanning , Nitric Oxide/blood , Peritoneal Lavage , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plant Stems/chemistry , Random Allocation , Resins, Plant/pharmacology , Resins, Plant/toxicity , Spectrophotometry, Infrared , Spleen/parasitology , Spleen/pathology , Survival Rate , Toxoplasma/drug effects , Toxoplasma/growth & development , Toxoplasma/ultrastructure , Toxoplasmosis, Animal/mortality
6.
Arch Toxicol ; 92(12): 3565-3583, 2018 12.
Article in English | MEDLINE | ID: mdl-30251054

ABSTRACT

Dammar resin is a natural food additive and flavoring substance present in many foods and drinks. The present study evaluates the chronic toxicity and carcinogenicity of dietary dammar resin in F344 rats. Dietary concentrations in the 52-week chronic toxicity study were 0, 0.03, 0.125, 0.5, or 2%. The major treatment-related deleterious effects were body weight suppression, increased relative liver weight, and low hemoglobin levels in males and females. Foci of cellular alteration in the liver were observed in the male 2% group, but not in any other group. The no-observed-adverse-effect level for chronic toxicity was 0.125% for males (200.4 mg/kg b.w./day) and females (241.9 mg/kg b.w./day). Dietary concentrations in the 104-week carcinogenicity study were 0, 0.03, 0.5, or 2%. Dammar resin induced hemorrhagic diathesis in males and females, possibly via the inhibition of extrinsic and intrinsic coagulation pathways. Incidences of hepatocellular adenomas and carcinomas were significantly increased in the male 2% group, but not in any other group. In the 4-week subacute toxicity study, the livers of male rat-fed diet-containing 2% dammar resin had increased levels of protein oxidation and increased the expression of two anti-apoptotic and seven cytochrome P450 (CYP) genes. There was also an increased tendency of oxidative DNA damage. These findings demonstrate that dammar resin is hepatocarcinogenic in male F344 rats and underlines the roles of inhibition of apoptosis, induction of CYP enzymes, and oxidative stress in dammar resin-induced hepatocarcinogenesis.


Subject(s)
DNA Damage/drug effects , Food Additives/toxicity , Liver/drug effects , Resins, Plant/toxicity , Animals , Apoptosis/drug effects , Body Weight/drug effects , Carcinogenicity Tests/methods , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Dose-Response Relationship, Drug , Female , Food Additives/administration & dosage , Hemoglobins/metabolism , Liver/pathology , Liver Neoplasms/chemically induced , Liver Neoplasms/pathology , Male , Oxidative Stress/drug effects , Rats , Rats, Inbred F344 , Resins, Plant/administration & dosage , Sex Factors , Toxicity Tests, Chronic/methods , Toxicity Tests, Subacute/methods
7.
BMC Complement Altern Med ; 18(1): 50, 2018 Feb 05.
Article in English | MEDLINE | ID: mdl-29402248

ABSTRACT

BACKGROUND: Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. METHODS: In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. RESULTS: In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. CONCLUSION: This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.


Subject(s)
Dracaena/chemistry , Resins, Plant/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Drinking/drug effects , Eating/drug effects , Female , Heart/drug effects , Kidney/drug effects , Male , Methanol , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Resins, Plant/administration & dosage , Toxicity Tests, Acute , Toxicity Tests, Subchronic
9.
Pharm Biol ; 55(1): 472-480, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27937036

ABSTRACT

CONTEXT: The resin from the trunk wood of Virola oleifera (Schott) A. C. Smith (Myristicaceae) is used in folk medicine to hasten wound repair and to treat pain and inflammatory conditions, and our previous report indicated the anti-oxidative properties in other oxidative stress model. OBJECTIVE: To investigate the protective effects of resin from V. oleifera in two experimental models of gastric ulcer oxidative-stress dependent. MATERIALS AND METHODS: Plant material was collected and the resin was subjected to partitioning with organic solvents. The buthanol fraction was subjected to chromatographic and spectrometric methods for isolation and structural elucidation. The resin was quantified for polyphenols and flavonoids by colorimetric methods. Furthermore, the antioxidant activity of resin was determined by three different methods. The ulcers were induced acutely in Swiss male mice with ethanol/HCl and indomethacin using single-doses of 10 and 100 mg/kg. The gastroprotection of the experimental groups was comparable to reference control lansoprazole (3 mg/kg). RESULTS: The high content of polyphenols (∼82%) and the presence of epicatechin and eriodictyol were determined. The LD50 was estimated at 2500 mg/kg. At minimum (10 mg/kg) and maximum (100 mg/kg) dosage of resin, both in ethanol/HCl as indomethacin ulcer induction models demonstrate reduction of lesions (minimum: ∼97% and ∼66%; maximum: ∼95% and ∼59%). DISCUSSION: The gastroprotection might be related to tannins, phenolic acids and flavonoids present in the resin by antioxidant properties. CONCLUSIONS: The results indicate that this resin has gastroprotective activity probably associated with the presence of phenolic antioxidant substances.


Subject(s)
Antioxidants/pharmacology , Gastric Mucosa/drug effects , Myristicaceae/chemistry , Plant Extracts/pharmacology , Resins, Plant/pharmacology , Stomach Ulcer/prevention & control , Animals , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/toxicity , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/toxicity , Benzothiazoles/chemistry , Chromatography, Thin Layer , Disease Models, Animal , Ethanol , Flavonoids/isolation & purification , Flavonoids/pharmacology , Gastric Mucosa/pathology , Hydrochloric Acid , Indomethacin , Lethal Dose 50 , Male , Mice , Phytotherapy , Plant Bark , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Plants, Medicinal , Polyphenols/isolation & purification , Polyphenols/pharmacology , Resins, Plant/chemistry , Resins, Plant/isolation & purification , Resins, Plant/toxicity , Solvents/chemistry , Spectrometry, Mass, Electrospray Ionization , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology , Sulfonic Acids/chemistry , Tandem Mass Spectrometry
10.
Proc Biol Sci ; 283(1822)2016 Jan 13.
Article in English | MEDLINE | ID: mdl-26763703

ABSTRACT

Growing evidence suggests that plant secondary compounds (PSCs) ingested by mammals become more toxic at elevated ambient temperatures, a phenomenon known as temperature-dependent toxicity. We investigated temperature-dependent toxicity in the desert woodrat (Neotoma lepida), a herbivorous rodent that naturally encounters PSCs in creosote bush (Larrea tridentata), which is a major component of its diet. First, we determined the maximum dose of creosote resin ingested by woodrats at warm (28-29°C) or cool (21-22°C) temperatures. Second, we controlled the daily dose of creosote resin ingested at warm, cool and room (25°C) temperatures, and measured persistence in feeding trials. At the warm temperature, woodrats ingested significantly less creosote resin; their maximum dose was two-thirds that of animals at the cool temperature. Moreover, woodrats at warm and room temperatures could not persist on the same dose of creosote resin as woodrats at the cool temperature. Our findings demonstrate that warmer temperatures reduce PSC intake and tolerance in herbivorous rodents, highlighting the potentially adverse consequences of temperature-dependent toxicity. These results will advance the field of herbivore ecology and may hone predictions of mammalian responses to climate change.


Subject(s)
Herbivory , Larrea/chemistry , Resins, Plant/toxicity , Sigmodontinae/physiology , Temperature , Toxins, Biological/metabolism , Animals , Climate Change , Feeding Behavior , Sigmodontinae/metabolism , Toxicity Tests
11.
J Pharm Pharmacol ; 67(12): 1744-55, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26407531

ABSTRACT

OBJECTIVES: The hormonal treatment for endometriosis frequently fails to completely eradicate endometriotic implants. A new therapeutic treatment is needed. This study investigates the in-vitro effect of Copaifera langsdorffii oil-resin on human eutopic and ectopic endometrium stromal cell cultures (EuESCs and EctESCs). METHODS: A nanocomposite system containing the copaiba oil-resin (NanoCOR) was developed and acute toxicity test was performed. Endometrial stromal cells (ESCs) from non-endometriotics controls (CESCs), EuESCs and EctESCs were isolated and treated with different concentrations of NanoCOR, at different time intervals to evaluate its effect on cell morphology, proliferation, viability, necrosis and apoptosis induction. KEY FINDINGS: When treated with 50 µg/ml of NanoCOR, the morphology of EctESCs changed, as the actin microfilaments were disorganized, disassembled or disrupted. Moreover, at 24 h of treatment with NanoCOR, the EctESCs viability was inhibited, and a significant number of these cells underwent apoptosis. In EuESCs, these effects were observed only at 48 h. Finally, the treatment of EctESCs with NanoCOR increased the lactate dehydrogenase release into the extracellular medium more than in EuESCs. CONCLUSIONS: Our data indicate that NanoCOR has a greater impact on the behaviour of human endometriotic stromal cells than on the eutopic endometrium stromal cells, supporting the idea that NanoCOR should be further investigated as a novel and valuable alternative to treat endometriosis.


Subject(s)
Cell Shape/drug effects , Endometriosis/drug therapy , Endometrium/drug effects , Fabaceae/chemistry , Plant Oils/pharmacology , Resins, Plant/pharmacology , Stromal Cells/drug effects , Trees , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/pathology , Animals , Apoptosis/drug effects , Case-Control Studies , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Endometriosis/pathology , Endometrium/pathology , Female , Humans , Male , Mice , Nanoparticles , Necrosis , Phytotherapy , Plant Oils/isolation & purification , Plant Oils/toxicity , Plants, Medicinal , Rainforest , Resins, Plant/isolation & purification , Resins, Plant/toxicity , Stromal Cells/pathology , Time Factors , Tropical Climate
12.
Curr Drug Deliv ; 12(4): 454-63, 2015.
Article in English | MEDLINE | ID: mdl-25895614

ABSTRACT

Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-ß-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Boswellia , Inflammation/prevention & control , Resins, Plant/pharmacology , Triterpenes/pharmacology , Administration, Oral , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/toxicity , Boswellia/chemistry , Carrageenan , Cellulose/chemistry , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Disease Models, Animal , Drug Carriers , Female , Indomethacin/pharmacology , Inflammation/chemically induced , Microscopy, Electron, Scanning , Phytotherapy , Plants, Medicinal , Polyethylene Glycols/chemistry , Rats, Wistar , Resins, Plant/administration & dosage , Resins, Plant/chemistry , Resins, Plant/isolation & purification , Resins, Plant/toxicity , Solubility , Solvents/chemistry , Spectrophotometry, Ultraviolet , Stomach Ulcer/chemically induced , Triterpenes/administration & dosage , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/toxicity
13.
Inhal Toxicol ; 25 Suppl 2: 34-45, 2013.
Article in English | MEDLINE | ID: mdl-24341845

ABSTRACT

CONTEXT: Cigarettes often have a small identifying mark (monogram) printed either on the cigarette paper toward the filter end of the cigarette or on the tipping paper. OBJECTIVE: A battery of tests was used to compare the toxicology of mainstream smoke from experimental cigarettes manufactured with different monogram inks. Cigarettes with different concentrations of different pigments were compared with cigarettes without ink, and with a control ink. MATERIALS AND METHODS: Smoke from each of the experimental cigarettes was evaluated using analytical chemistry and in vitro bacterial mutagenicity (Salmonella, five strains, ± S9) and cytotoxicity (neutral red uptake) assays. RESULTS: No differences were observed between experimental cigarettes printed with three different pigment loads of iron oxide-based Black pigment and non-printed cigarettes. In general, no dose response was observed. However, increases in certain smoke constituents were found to correlate with Pigment Yellow 14 (also known as benzidine yellow) and Pigment Blue 15 (copper phthalocyanine). Increases in bacterial mutagenicity were observed for high-level print of Pigment Yellow 14 in TA98 and TA1537 and the high-level print of Pigment Blue 15 in TA98. In vitro cytotoxicity of mainstream smoke was unaffected by the presence of monogram ink on cigarettes. CONCLUSION: Statistically significant dose-responsive constituent changes and an increase in mutagenicity were observed with inclusion of Pigment Yellow 14 and Pigment Blue 15. Other pigments showed minimal toxicological activity.


Subject(s)
Coloring Agents/toxicity , Consumer Product Safety , Ink , Smoke/adverse effects , Tobacco Products/toxicity , Adhesives/chemistry , Adhesives/toxicity , Air Filters , Animals , BALB 3T3 Cells , Cell Survival/drug effects , Cellulose/analogs & derivatives , Cellulose/chemistry , Cellulose/toxicity , Coloring Agents/chemistry , Lethal Dose 50 , Linseed Oil/chemistry , Linseed Oil/toxicity , Materials Testing , Mice , Mutagenicity Tests , Mutagens/analysis , Mutagens/chemistry , Mutagens/toxicity , Paper , Resins, Plant/chemistry , Resins, Plant/toxicity , Smoke/analysis , Nicotiana/chemistry , Nicotiana/toxicity , Tobacco Products/analysis , Toxicity Tests
14.
Mutat Res ; 748(1-2): 29-35, 2012 Oct 09.
Article in English | MEDLINE | ID: mdl-22766412

ABSTRACT

Dammar resin has long been used in foods as either a clouding or a glazing agent. In a recent study, 2% Dammar resin showed significant hepatocarcinogenicity in a rat 2-year bioassay. Therefore, for an accurate estimate of human risk, it is necessary to understand whether Dammar resin induces liver genotoxicity and the underlying mechanisms of its hepatocarcinogenicity. Modifying effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a typical genotoxic carcinogen produced during cooking of protein-rich foods, was also studied in the present study. Exposure of gpt delta mice to Dammar resin at a dose of 2% for 12 weeks did not induce any obvious mutagenicity in the liver. However, the index of cell proliferation, the level of 8-OHdG, and bax, bcl-2, p53, cyp1a2, cyp2e1, gpx1 and gstm2 gene expression were all significantly increased when compared with the control group. In the IQ treatment group, at a dose of 300ppm, mutagenicity was readily detected, the index of cell proliferation increased, and p53, cyp2e1 and gpx1 gene expression was down-regulated in the liver. Down-regulation of p53, P450s, and gpx1 in the livers of IQ treated mice are consistent with its genotoxic mechanism of carcinogenicity observed in a 675-day study. In contrast, our results using gpt delta mice suggest that Dammar resin is not genotoxic. Instead, the Dammar resin-induced hepatocarcinogenicity seen in our previous 2-year study with rats may have been mediated by non-genotoxic mechanisms, including increased P450 enzyme activity, increased oxidative stress, altered gene expression, and promotion of cell proliferation.


Subject(s)
Carcinogens/toxicity , DNA Damage , Food Additives/toxicity , Hypoxanthine Phosphoribosyltransferase/genetics , Mice, Transgenic , Mutagens/toxicity , Plant Extracts/toxicity , Quinolines/toxicity , Resins, Plant/toxicity , Animals , Body Weight/drug effects , Cell Proliferation/drug effects , Cytochrome P-450 Enzyme System/metabolism , Liver/drug effects , Male , Mice , Oxidative Stress
15.
Asian Pac J Trop Biomed ; 2(3): 210-4, 2012 Mar.
Article in English | MEDLINE | ID: mdl-23569899

ABSTRACT

OBJECTIVE: To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. METHODS: In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2 500 and 5 000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. RESULTS: The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5 000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. CONCLUSIONS: The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia.


Subject(s)
Minerals/administration & dosage , Minerals/toxicity , Resins, Plant/administration & dosage , Resins, Plant/toxicity , Animals , Case-Control Studies , Female , Liver/drug effects , Liver/pathology , Male , Rats , Rats, Wistar , Spleen/drug effects
16.
Inhal Toxicol ; 23 Suppl 1: 41-69, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21651429

ABSTRACT

CONTEXT: A total of 32 essential oils and resins were added individually to experimental cigarettes. OBJECTIVE: A battery of tests was used to compare the toxicity of mainstream smoke from these experimental cigarettes. The lowest target inclusion level was 100 ppm and the highest was 100,000 ppm. MATERIALS AND METHODS: Smoke from each of the experimental cigarette was evaluated using analytical chemistry and in vitro bacterial (Salmonella, five strains) mutagenicity and cytotoxicity (neutral red uptake) assays. For seven of the ingredients (carob bean, carob bean extract, carrageenan, chamomile flower Hungarian oil, guar gum, peppermint oil, and spearmint oil), 90-day smoke inhalation studies with rats were also performed. RESULTS: In general, inclusion levels resulted in minimal changes in smoke chemistry; the exceptions were PO and SO, where reductions to 40-60% of control values were noted, possibly indicating a tobacco displacement effect. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for a dose-related reduction in cytotoxicity for SO. There were very few statistically significant differences within any of the seven inhalation studies; when present, the differences were sporadic and inconsistent between sexes. The addition of SO appeared to depress body weight gain and increase the atrophy of olfactory epithelia, but only in males. CONCLUSION: The essential oils and resins tested here as ingredients in experimental cigarettes show minimal toxicological sequelae, even at high inclusion levels. The highest inclusion level for SO showed some equivocal responses.


Subject(s)
Nicotiana/toxicity , Oils, Volatile/toxicity , Resins, Plant/toxicity , Smoking/adverse effects , Xenobiotics/toxicity , Administration, Inhalation , Animals , Body Weight/drug effects , Cell Survival/drug effects , Cells, Cultured , Excipients/analysis , Excipients/toxicity , Female , Flavoring Agents/analysis , Flavoring Agents/toxicity , Male , Oils, Volatile/analysis , Rats , Rats, Sprague-Dawley , Resins, Plant/analysis , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Smoke/adverse effects , Smoke/analysis , Nicotiana/chemistry , Toxicity Tests
17.
Chem Biodivers ; 7(8): 1871-84, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20730953

ABSTRACT

Nineteen known triterpenoids, 1-19, and one known sesquiterpenoid, 20, were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid (1), was converted to fourteen derivatives, namely, an alcohol, 21, an aldehyde, 22, and twelve L-amino acid conjugates, 23-34. Compounds 1-34 were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12-14, 16, and 17, showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of beta-carotene, a known natural antitumor promoter. In addition, (20S)-20-hydroxy-3,4-secodammara-4(28),24-dien-3-al (22) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1-34 against human cancer cell lines showed that reduction (i.e., 21 and 22) or conjugation with L-amino acids (i.e., 23-34) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Resins, Plant/pharmacology , Resins, Plant/toxicity , Triterpenes/pharmacology , Triterpenes/toxicity , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dipterocarpaceae/chemistry , Humans , Mice , Molecular Structure , Papilloma/drug therapy , Resins, Plant/chemistry , Skin Neoplasms/drug therapy , Triterpenes/chemistry
18.
Pharm Biol ; 48(3): 242-6, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20645807

ABSTRACT

Several Ferula (Umbelliferae) species have been used in Iranian traditional medicine as antiflatulent, antispasmodic, anticonvulsant, expectorant, etc. In the present study, cytotoxicity and anticonvulsant activity of the methanol extracts from several Ferula species were evaluated. Air-dried samples of different parts of these plants (Ferula diversivittata Regel & Schmalh. (roots), Ferula persica Willd. (aerial parts), Ferula ovina (Boiss.) Boiss. (roots), Ferula badrakema Kos.-Pol. (roots), Ferula diversivittata (flowers), Ferula latisecta Rech. F. & Aell. (roots), and Ferula badrakema (fruits)) were macerated with methanol for 3 days. The mixtures were then filtered, concentrated and dried. For determination of the cytotoxicity of the extracts and also the oleo-gum-resin of F. assafoetida L., the brine shrimp (Artemia salina) was employed as a model assay system since it provides a convenient in-house pre-screening method for evaluating general cytotoxicity. The methanol extracts of different Ferula species and the oleo-gum-resin of F. assafoetida exhibited cytotoxic effect with LC(50) values in the range of 6-321 microg/mL. For the anticonvulsant testing, seizure was induced by injection of pentylenetetrazole (PTZ), 90 mg/kg intraperitoneally (i.p.). This dose was given to 10 groups, each consisting of 6 mice, which were pretreated i.p. with the extracts (300 mg/kg), Diazepam (10 mL/kg) or saline (10 mL/kg). The results showed that none of the tested Ferula species can prevent PTZ-induced seizure at the used dose. In conclusion, all of the extracts and the oleo-gum resin of F. assafoetida showed dose-dependent cytotoxicity which was highest in F. badrakema fruits and lowest in F. badrakema roots. Our findings also revealed that the methanol extracts and F. assafoetida oleo-gum resin do not possess anticonvulsant activity.


Subject(s)
Anticonvulsants/therapeutic use , Ferula/chemistry , Medicine, Traditional , Phytotherapy , Plant Extracts/toxicity , Plant Extracts/therapeutic use , Seizures/prevention & control , Animals , Artemia/drug effects , Convulsants/toxicity , Iran , Lethal Dose 50 , Male , Mice , Pentylenetetrazole/toxicity , Resins, Plant/therapeutic use , Resins, Plant/toxicity , Seizures/chemically induced
19.
Rev. méd. Minas Gerais ; 20(2,supl.2): S84-S87, abr.-jun. 2010.
Article in Portuguese | LILACS | ID: lil-562249

ABSTRACT

Relata-se, neste artigo, um caso de Dermatite de Contato Alérgica (DCA) Ocupacional à resina de Pinus oocarpa em uma trabalhadora rural atendida no Centro de Referência Estadual em Saúde do Trabalhador de Minas Gerais (CEREST/MG). Trata-se de patologia comum e com repercussões financeiras importantes. O objetivo do trabalho é relatar, discutir e chamar a atenção da classe médica em geral para a causa ocupacional da DCA, que pode causar um impacto significativo na qualidade de vida dos trabalhadores.


A case report of an Occupational Allergic Contact Dermatitis (ACD) caused by Pinus oocarpa resin in a female rural worker referred to the Worker's Health State Reference Center of Minas Gerais (CEREST/MG). The disease is extremely frequent and may pose an appreciable economic impact. The objective of this paper is to report, discuss and alert the doctors about the occupational cause of ACD, a disease that may produce an important impact on workers' quality of life.


Subject(s)
Humans , Female , Adult , Dermatitis, Allergic Contact/economics , Pinus/toxicity , Resins, Plant/toxicity , Occupational Diseases
20.
Water Environ Res ; 82(5): 440-6, 2010 May.
Article in English | MEDLINE | ID: mdl-20480765

ABSTRACT

Benthal solids accumulated in aerated stabilization basins (ASBs) must be dredged to regain treatment capacity. While dredging restores treatment performance, it has been associated occasionally with the failure to meet regulatory effluent toxicity limits at the time of dredging. A first study of its kind was undertaken to investigate the implications of ASB dredging on potential effluent toxicity to fish. The study showed that benthal solid slurry removed from the quiescent zone of an ASB with a hydraulic dredge was toxic to rainbow trout with a 96-hour median lethal concentration (LC50) of 2.2%. The high ammonia concentration in the sample was the main cause of fish mortality. Hydrogen sulfide and resin and fatty acids also were present in the dredged material at concentrations that could cause fish mortality. These findings have led to best management practices that can be used to mitigate or eliminate fish toxicity issues during dredging operations.


Subject(s)
Industrial Waste/adverse effects , Oncorhynchus mykiss , Waste Disposal, Fluid , Water Pollutants, Chemical/toxicity , Ammonia/toxicity , Animals , Bacteria/metabolism , Fatty Acids/toxicity , Hydrogen Sulfide/toxicity , Hydrogen-Ion Concentration , Oxygen/chemistry , Oxygen/metabolism , Paper , Resins, Plant/toxicity , Water Pollution, Chemical/legislation & jurisprudence , Water Pollution, Chemical/prevention & control
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