Neuroprotective effect of standardized extracts of three Lactuca sativa Linn. varieties against 3-NP induced Huntington's disease like symptoms in rats.

OBJECTIVES: The study was aimed to evaluate the efficacy of three commonly consumed Lactuca sativa (LS) Linn. varieties viz., Grand rapid, Lollo rosso and Iceberg (Asteraceae) against 3-NP induced HD like symptoms in rats. METHODS: Ethanol extracts of leaves of three LS varieties were prepared, and standardized on the basis of quercetin content using HPLC. These extracts (100 and 200 mg kg, p.o. for 20 days) were evaluated for their neuroprotective effect against 3-NP (10 mg/kg, i.p. for 14 days) induced neurotoxicity in male Wistar rats. The extract that exhibited maximum activity was successively fractionated using hexane, ethyl acetate, n-butanol and aqueous in increasing order of polarity. These fractions were also evaluated (dose equivalent to the dose of the extract of LS variety exhibiting maximum activity) for their neuroprotective effect. The protective effect of extracts and fractions was evaluated using different behavioral (rota rod, actophotometer, beam walk and Morris water maze) and biochemical (malondialdehyde, nitrite, superoxide dismutase, catalase and reduced glutathione) parameters. RESULTS: 3-NP elicit marked deterioration in motor coordination, locomotor activity and memory in comparison to control group. Standardized ethanol extract of grand rapid (200 mg/kg) exhibited maximum activity amongst the three tested varieties. Therefore, its fractions were also evaluated, and n-butanol fraction (40 mg/kg) exhibited maximum attenuation of 3-NP induced HD like symptoms which was evident from improved behavioral and biochemical parameters. DISCUSSION: The results exhibit that LS (Grand rapid variety) prophylaxis mitigated 3-NP induced neurotoxicity and HD like symptoms in rats due to its potent antioxidant potential.

Exposure to 1-Butanol Exemplifies the Response of the Thermoacidophilic Archaeon Sulfolobus acidocaldarius to Solvent Stress.

Sulfolobus acidocaldarius is a thermoacidophilic crenarchaeon with optimal growth at 80°C and pH 2 to 3. Due to its unique physiological properties, allowing life at environmental extremes, and the recent availability of genetic tools, this extremophile has received increasing interest for biotechnological applications. In order to elucidate the potential of tolerating process-related stress conditions, we investigated the response of S. acidocaldarius toward the industrially relevant organic solvent 1-butanol. In response to butanol exposure, biofilm formation of S. acidocaldarius was enhanced and occurred at up to 1.5% (vol/vol) 1-butanol, while planktonic growth was observed at up to 1% (vol/vol) 1-butanol. Confocal laser-scanning microscopy revealed that biofilm architecture changed with the formation of denser and higher tower-like structures. Concomitantly, changes in the extracellular polymeric substances with enhanced carbohydrate and protein content were determined in 1-butanol-exposed biofilms. Using scanning electron microscopy, three different cell morphotypes were observed in response to 1-butanol. Transcriptome and proteome analyses were performed comparing the response of planktonic and biofilm cells in the absence and presence of 1-butanol. In response to 1% (vol/vol) 1-butanol, transcript levels of genes encoding motility and cell envelope structures, as well as membrane proteins, were reduced. Cell division and/or vesicle formation were upregulated. Furthermore, changes in immune and defense systems, as well as metabolism and general stress responses, were observed. Our findings show that the extreme lifestyle of S.acidocaldarius coincided with a high tolerance to organic solvents. This study provides what may be the first insights into biofilm formation and membrane/cell stress caused by organic solvents in S. acidocaldariusIMPORTANCEArchaea are unique in terms of metabolic and cellular processes, as well as the adaptation to extreme environments. In the past few years, the development of genetic systems and biochemical, genetic, and polyomics studies has provided deep insights into the physiology of some archaeal model organisms. In this study, we used S. acidocaldarius, which is adapted to the two extremes of low pH and high temperature, to study its tolerance and robustness as well as its global cellular response toward organic solvents, as exemplified by 1-butanol. We were able to identify biofilm formation as a primary cellular response to 1-butanol. Furthermore, the triggered cell/membrane stress led to significant changes in culture heterogeneity accompanied by changes in central cellular processes, such as cell division and cellular defense systems, thus suggesting a global response for the protection at the population level.

Metabolites of Aliphatic Alcohols Detected in Alcoholic Beverages Inhibit Phagocytosis.

AIMS: The aim of our study was to measure granulocyte and monocyte phagocytosis following treatment of cells with some metabolites of aliphatic alcohols alone and in combination with acetaldehyde. METHODS: The cells were separated from human peripheral blood prior to determination of phagocytosis of opsonized zymosan particles by granulocytes and monocytes treated individually with metabolites of aliphatic alcohols including formaldehyde, 1-propanal, acetone, 1-butanal, and 2-butanone and in combination with acetaldehyde. RESULTS: The findings revealed that metabolites of aliphatic alcohols inhibited phagocytosis by granulocytes and monocytes in a concentration-dependent manner and when combined with acetaldehyde, they caused a further decrease in phagocytic activity. CONCLUSION: Due to their additive effects, it is possible that, in combination with acetaldehyde, metabolites of aliphatic alcohols may inhibit phagocytosis at physiologically realistic concentrations in episodic heavy drinkers, thereby contributing to their increased susceptibility to infectious diseases.

Butanol fraction of Alstonia boonei De Wild. leaves ameliorate oxidative stress and modulate key hypoglycaemic processes in diabetic rats.

OBJECTIVE: The effect of Alstonia boonei fractions on glucose homeostasis was investigated via in vitro enzyme inhibition activity, ex vivo glucose uptake assay, and in vivo methods in diabetic rats. METHODOLOGY: A. boonei fractions were subjected to in vitro α-glucosidase inhibitory assay and then ex vivo glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the in vivo assay since it showed more activity in the initial tests conducted. ABBF was administrated via oral dosing to six-weeks old fructose-fed STZ-induced type 2 diabetic rats over a 5-week experimental period. RESULTS: ABBF treatment at a low dose of 150 mg/kg bw, significantly (p < .05) reduced blood glucose level, enhanced oral glucose tolerance ability, restored insulin secretion and hepatic glycogen synthesis as well as promoted islet regeneration than the high dose (300 mg/kg bw). CONCLUSION: These results suggest that ABBF could be exploited as a therapeutic potential for treating T2D.

Effect of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and benzo[a]pyrene exposure on the development of metabolic syndrome in mice.

AIM: The prevalence of metabolic syndrome (MetS), a cluster of serious medical conditions that raise the risk of lung cancer, has increased worldwide. Tobacco smoking (TS) potentially increases the risk of developing MetS. Despite the potential association of MetS with lung cancer, preclinical models that mimic human diseases, including TS-induced MetS, are limited. Here we evaluated the impact of exposure to tobacco smoke condensate (TSC) and two representative tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNK) and benzo[a]pyrene (BaP), on MetS development in mice. MATERIALS AND METHODS: FVB/N or C57BL/6 mice were exposed to vehicle, TSC, or NNK and BaP (NB) twice weekly for 5 months. The serum levels of total cholesterol (TCHO), triglycerides, high-density lipoprotein (HDL), blood glucose, and metabolites, along with glucose tolerance and body weight, were measured. KEY FINDINGS: Compared with those of vehicle-treated mice, mice with TSC or NB exposure displayed major phenotypes associated with MetS, including increased serum levels of TCHO, triglycerides, and fasting and basal blood glucose and decreased glucose tolerance, and serum levels of HDL. These MetS-associated changes were found in both FVB/N and C57BL/6 mice that were susceptible or resistant to carcinogen-induced tumorigenesis, respectively, indicating that tumor formation is not involved in the TSC- or NB-mediated MetS. Moreover, oleic acid and palmitoleic acid, which are known to be associated with MetS, were significantly upregulated in the serum of TSC- or NB-treated mice compared with those in vehicle-treated mice. SIGNIFICANCE: Both TSC and NB caused detrimental health problems, leading to the development of MetS in experimental mice.

Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin-induced pulmonary fibrosis based on metabolomics.

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor ß (TGF-ß) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-ß1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-ß1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model.

Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)-Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)-Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)-Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)-Combination 4; provided ~30% (30 ± 1.1), 70% (12 ± 0.4; P < 0.01), 60% (19 ± 0.2; P < 0.05) and 90% (05 ± 0.1; P < 0.001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0.3) protection (P > 0.05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P < 0.05-0.001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3rd hour of cisplatin administration. In continuation, at the 18th of cisplatin administration reduction in dopamine (P < 0.001) in the AP and 5HT in the brain stem and intestine (P < 0.001) was observed. The said combination did not change the neurotransmitters basal levels and their respective metabolites any significantly. In conclusion, all the tested combinations offered protection against cisplatin induced vomiting to variable degrees, where combination 4 provided enhanced attenuation by antiserotonergic mechanism at the 3rd hour while a blended antidopaminergic and antiserotonergic mechanism at the 18th hour after cisplatin administration.

Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session.

OBJECTIVES: To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure. DESIGN: Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure. SETTINGS: Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. PARTICIPANTS: 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls. OUTCOME MEASURES: 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels. RESULTS: MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls. CONCLUSIONS: MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.

BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. OBJECTIVES: The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. METHOD: Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. RESULTS: The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. CONCLUSION: We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

A review of the environmental fate and aquatic effects of a series of C4 and C8 oxo-process chemicals.

Environmental fate and aquatic effects data were examined for a series of C4 (butyl acetate, 1-butanol, isobutyl alcohol) and C8 (2-ethylhexanol and 2-ethylhexanoic acid) oxo-process chemicals. Manufacturing of these chemicals requires enclosed equipment, so environmental releases are generally limited to volatilization during their use, handling or transport. C4 compounds are more soluble and volatile, and would bind to soil and sediment to a lesser extent than C8 compounds. All five compounds were readily biodegradable based on OECD and APHA tests conducted up to 28 days. Atmospheric photo-oxidation half-lives range from 0.43 to 3.8 days. Toxicity data show that all five compounds pose generally low concern to fish, invertebrates, algae, and microorganisms. Overall, the data show that inadvertent releases of these compounds into the environment would be rapidly biodegraded in soil and water, volatilize to the atmosphere subject to photo-oxidation, while any residues remaining in water would pose a negligible threat to aquatic life.

Time course of sensory eye irritation in humans exposed to N-butanol and 1-octene.

In this study, we investigated the time course effect of sensory eye irritation in 16 subjects exposed (i.e., eye only) to n-butanol and 1-octene. Half the subjects were exposed to n-butanol, and the remaining subjects were exposed to 1-octene. Each subject was studied on 5 different days; during each day each subject was exposed in three runs (i.e., run 1, run 2, and run 3) to a constant concentration of either n-butanol or 1-octene. We performed run 1 and run 3, both of which lasted 15 min each, to evaluate persistence in "sensitization." We performed run 2, which lasted 60 min, to study the time course of sensory irritation. Ratings of ocular irritation intensity were obtained continuously during all three runs. The exposure concentrations for n-butanol were 0 mg/m3, 300 mg/m3, 900 mg/m3, and 3 000 mg/m3, and the exposure concentrations for 1-octene were 0 mg/m3, 6 000 mg/m3, 10 400 mg/m3, and 18 000 mg/m3. During run 2, we observed a slight increase in perceived eye irritation intensity for the lower concentrations of 1-octene and for all exposure concentrations of n-butanol. However, the threshold for irritation was clearly exceeded for only the 1-octene 10 400-mg/m3 and 18 000-mg/m3 exposures. During these two exposures, the response increased 10-fold following 20-40 min of exposure during run 2, after which the response remained constant. We investigated the existence of persistence in "sensitization" by comparing intensity of responses between run 1 and run 3. Persistence in "sensitization" was apparent for only the 1-octene exposure.

[Obstructive sleep apnea syndrome caused by occupational exposure to solvents]. / Obstruktives Schlafapnoesyndrom durch eine berufliche Lösungsmittelexposition.

HISTORY AND ADMISSION FINDINGS: A 52-year-old man working in a chemical laboratory was referred with the possible diagnosis of toxic encephalopathy. For 17 years he had been exposed to high concentrations of perchlorethylene and n-butanol vapours which every day had caused acute symptoms of organic solvent intoxication. Current complaints were autonomic nervous system symptoms, loss of concentration and memory, and fatigue in the second half of the day. The patient was obese but in good general condition. INVESTIGATIONS: Neuropsychiatric examination confirmed the reported loss of concentration and planning ability at work. The polysomnogram indicated an increased number of largely obstructive apnoea attacks. DIAGNOSIS, TREATMENT AND COURSE: As the patients had an obstructive type of sleep apnoea treatment consisted of positive pressure ventilation at night and weight reduction. The occupational exposure to organic solvents was the likely cause. CONCLUSIONS: As the symptoms of encephalopathy and sleep apnoea syndrome overlap, the latter should be considered before an encephalopathy is diagnosed. Because a rare cause of the sleep apnoea syndrome is prolonged and marked occupational exposure to organic solvents this should be asked about in taking the history. If indeed there has been occupational exposure, it should cease at once and be reported.

Irritation of the human eye mucous membrane caused by airborne pollutants.

OBJECTIVES: The purpose of this study was to investigate the different irritative effects of carbon dioxide and n-butanol exposure on the ocular mucous membrane. MATERIAL AND METHODS: Provocation by the gases was at the same sensory level, which was 50% of maximum on a linear scale. The experiment was performed on nine healthy subjects with the aim of identifying the relationship between eye irritation and the human physiological response to this irritation. A goggle exposure system, invented at the Department of Occupational and Environmental Medicine, Aarhus University, was used for the experiment. The exposures lasted for 30 min each. RESULTS: There were no changes in tear film stability and conjunctival corrosion (lissamine staining) after carbon dioxide and n-butanol exposures leading to 50% sensory eye irritation. However, the study showed a delayed inflammatory response after carbon dioxide exposure when compared with clean air. The significant change was seen for tear fluid neutrophilic granulocytes 22 h after carbon dioxide (CO(2)) exposure only. CONCLUSIONS: It is concluded that the type of exposure made no difference to the elicited physiological responses and that tear film stability and epithelium damage were not affected by sensory irritation itself.