Metabolic disposition of a monoterpene ketone, piperitenone, in rats: evidence for the formation of a known toxin,p-cresol

It was shown earlier that the monoterpene ketone, piperitenone (I) is one of the major metabolites of R-(+)-pulegone, a potent hepatotoxin. In the present studies, the metabolic disposition of piperitenone (I) was examined in rats. Piperitenone (I) was administered orally (400 mg/kg of the b. wt./day) to rats for 5 days. The following urinary metabolites were isolated and identified by various spectral analyses: p-cresol (VI), 6,7-dehydromenthofuran (III), p-mentha-1,3,5,8-tetraen-3-ol (IX), p-mentha-1, 3,5-triene-3, 8-diol (X), 5-hydroxypiperitenone (VIII), 7-hydroxypiperitenone (XI), 10-hydroxypiperitenone (XII), and 4-hydroxypiperitenone (VII). Incubation of piperitenone (I) with phenobarbital-induced rat liver microsomes in the presence of NADPH resulted in the formation of five metabolites which have been tentatively identified as metabolites III, VII, VIII, XI, XII, on the basis of gas chromatography retention time and gas chromatography-mass spectrometry analysis. Based on these results, a probable mechanism for the formation of p-cresol from piperitenone (I) via the intermediacy of metabolite III has been proposed

Role of neutral metabolites in microbial conversion of 3ß-acetoxy-19-hydroxycholest-5-ene into estrone

Biotransformation of 3ß-acetoxy-19-hydroxycholest-5-ene (19-HCA, 6 g) by Moraxella sp. was studied. Estrone (712 mg) was the major metabolite formed. Minor metabolites identified were 5α-androst-1-en-19-ol-3,17-dione (33 mg), androst-4-en-19-ol-3,17-dione (58 mg), androst-4-en-9α,19-diol-3,17-dione (12 mg), and androstan-19-ol-3,17-dione (1 mg). Acidic metabolites were not formed. Time course experiments on the fermentation of 19-HCA indicated that androst-4-en-19-ol-3,17-dione was the major metabolite formed during the early stages of incubation. However, with continuing fermentation its level dropped, with a concomitant increase in estrone. Fermentation of 19-HCA in the presence of specific inhibitors or performing the fermentation for a shorter period (48 h) did not result in the formation of acidic metabolites. Resting-cell experiments carried out with 19-HCA (200 mg) in the presence of α,α'-bipyridyl led to the isolation of three additional metabolites, viz., cholestan-19-ol-3-one (2 mg), cholest-4-en-19-ol-3-one (10 mg), and cholest-5-en-3ß,19-diol (12 mg). Similar results were also obtained when n-propanol was used instead of α,α'-bipyridyl. Resting cells grown on 19-HCA readily converted both 5α-androst-1-en-19-ol-3,17-dione and androst-4-en-19-ol-3,17-dione into estrone. Partially purified 1,2-dehydrogenase from steroid-induced Moraxella cells transformed androst-4-en-19-ol-3,17-dione into estrone and formaldehyde in the presence of phenazine methosulfate, an artificial electron acceptor. These results suggest that the degradation of the hydrocarbon side chain of 19-HCA does not proceed via C22 phenolic acid intermediates and complete removal of the C17 side chain takes place prior to the aromatization of the A ring in estrone. The mode of degradation of the sterol side chain appears to be through the fission of the C17-C20 bond. On the basis of these observations, a new pathway for the formation of estrone from 19-HCA in Moraxella sp. has been proposed

Asymmetric reduction of prochiral ketones by cell-free systems from Alcaligenes eutrophus

A strain of Alcaligenes eutrophus has been isolated from the soil by enrichment culture technique with nerolidol (1), a sesquiterpene alcohol, as the sole source of carbon and energy. Fermentation of nerolidol (1) by this bacterium in a mineral salts medium resulted in the formation of two major metabolites, viz. geranylacetone (2) and an optically active alcohol, (S)-(+)-geranylacetol (3). Nerolidol (1)-induced cells readily transformed 1,2-epoxynerolidol (4) and 1,2-dihydroxynerolidol (5) into geranylacetone (2). These cells also exhibited their ability to carry out stereospecific reduction of 2 into (S)-(+)-geranylacetol (3). Oxygen uptake studies clearly indicated that nerolidol-induced cells oxidized compounds 2, 3, 4, 5 and ethyleneglycol (7). Based on the nature of the metabolites isolated, the ability of nerolidol-induced cells to convert compounds 4 and 5 into geranylacetone (2), and oxygen uptake studies, a pathway for the microbial degradation of nerolidol (1) has been proposed. The proposed pathway envisages the epoxidation of the terminal double bond, opening of the epoxide and cleavage between C-2 and C-3 in a manner similar to the periodate oxidation of cis-diol. The cell-free extract prepared from nerolidol-induced cells readily carried out the asymmetric reduction of compound 2 to an optically active alcohol (3) in the presence of NAD(P)H. The cell-free extract carried out both oxidation and reduction reactions at two different pH values and exhibited wide substrate specificity towards various steroids besides terpenes

Study of profile of poisoning cases reported to district hospital, Chamarajanagar, Karnataka, India

Background: Poisoning is a major public health problem worldwide, with thousands of deaths occurring every year, mainly in the developing countries. India, holding 70% of agricultural land, accounts for one third of pesticide poisoning cases in the third world, the farm workers being the worst affected. Most of the poisonings occur due to deliberate self-ingestion of the poison. Organo-phosphorus (OP) compounds occupy the greatest burden of poisoning related morbidity and mortality. The present study was aimed to know the profile of various poisoning cases admitted to emergency department in district hospital, Chamarajanagar, Karnataka, India. The main objectives of this study were to determine the profile of poisoning cases reported to district hospital, Chamarajanagar and to assess their pattern and outcome.Methods: A record based retrospective study for the year 2012 i.e. from 1st January 2012 to 31st December 2012 was conducted in district hospital, Chamarajanagar, Karnataka, India and the data regarding age, gender, residence, time elapsed after intake, type of poison, manner and route of poisoning, duration of hospitalization and outcome were collected in a pre-structured proforma. The data was analyzed using standard statistical methods.Results: In present study, rural hindu males were among the highest reported cases, with maximum number of cases reported during the month of March and during the 12:01 to 18:00 hours of the day. Irritant poisons accounts to the highest incidence (68%) among poisoning in present study. Pesticides, organophosphorus compound in particular form the major type of poisons among irritants followed by snake bite, rat poison and honey bee bite (sting). Conclusions: This study highlights the profile of poisoning cases admitted to the Chamarajanagar District, Karnataka, India which clearly indicates the high risk population involved and the common poisons encountered in these region

Effect of ring size in R-(+)-pulegone-mediated hepatotoxicity: studies on the metabolism of R-(+)-4-methyl-2-(1-methylethylidene)-cyclopentanone anddl-camphorone in rats

R-(+)-Pulegone, a monoterpene ketone, is a potent hepatotoxin. The present study was designed to evaluate whether the reduction of the ring size in R-(+)-pulegone would affect its mode of metabolism and its hepatotoxic potential. Metabolic fate ofR-(+)-4-methyl-2-(1-methylethylidene)-cyclopentanone (I) and 5-methyl-2-(1-methylethylidene)-cyclopentanone (dl-camphorone; II) were examined in rats. Compounds I and II were administered orally (250 mg/kg of b.wt./day) to rats for 5 to 7 days. The following metabolites were isolated and identified from the urine of rats dosed with I: 3-methyl-5-(1-methylethylidene)-cyclopent-2-enone (Ie), Z-4-methyl-2-(1-hydroxymethylethylidene)-cyclopentanone (Ib), E-4-methyl-2-(1-hydroxymethylethylidene)-cyclopentanone (Ia), 3-hydroxy-4-methyl-2-(1-methylethylidene)-cyclopentanone (If), 4-hydroxy-4-methyl-2-(1-methylethylidene)-cyclopentanone (Ic), and E-4-methyl-2-(1-carboxyethylidene)-cyclopentanone (Id). Phenobarbital (PB)-induced rat liver microsomes in the presence of NADPH transformed compound I into metabolites, which were identified as Ia, Ib, Ic, Ie, and If. The following urinary metabolites were isolated and identified from compound II: 5-hydroxy-5-methyl-2-(1-methylethylidene)-cyclopentanone (IIc), 5-hydroxy-5-methyl-2-(1-methylethyl)-cyclopentanone (IIg), Z-5-methyl-2-(1-hydroxymethylethylidene)-cyclopentanone (IIb), 5-methyl-2-(1-hydroxymethylethyl)-cyclopentanone (IIf), E-5-methyl-2-(1-hydroxymethylethylidene)-cyclopentanone (IIa), E-5-methyl-2-(1-carboxyethylidene)-cyclopentanone (IId), and 5-methyl-2-(1-carboxyethyl)-cyclopentanone (IIe). PB-induced rat liver microsomes in the presence of NADPH were shown to transform compound II to IIa, IIb, and IIc. Studies carried out in vitro demonstrated that hydroxylation at the tertiary carbon atom or oxidation of the isopropylidene methyl groups in II can be specifically blocked through structural modifications as seen in compounds 2,2-dimethyl-5-(1-methylethylidene)-cyclopentanone (III) and 5-methyl-2-(1-ethyl-1-propylidene)-cyclopentanone (IV). Similar observation was also made when isopropylidene methyl groups inR-(+)-pulegone were replaced by ethyl groups. Intraperitoneal administration of a single dose (250 mg/kg) of I and II to rats did not elicit hepatotoxicity as judged by serum alanine aminotransaminase levels and liver microsomal drug metabolizing enzyme activities

Gambaran Depresi pada ODHA Perempuan yang Tinggal di Jakarta

Indonesia is the one of the countries in the world with the epidemic transmission of HIV, which continues to grow. The transmission of HIV and AIDS is again related to risky of behavior and population key. In fact many couples who are contracting a partner who had behavior risk. In Indonesia the number of women who are infected increases. This indicates the susceptibility of women to HIV infection and AIDS. This descriptive study aims to discuss the depression in ODHA women who live in Jakarta. The method used is qualitative with the interviews. The respondents involved in this research were two adult female ODHA which are beginning with the age of the 21- 40 years and suffer from depression in accordance with depression in BDI-II. Data analysis revelaed the different levels of depression that women were affected from their experienced problems, the disclosure status of HIV, the stigma and discrimination, and social support. In addition, the issues of this women who affected with HIV were parenting and caring family members and they were the person who support their families. From the two respondents this study discovered that both have negative thinking to themselves, experience, and future.Depression &nbsp

Structure of pregna-4,16-diene-7α,14α-diol-3,20-dione

7α,14α-Dihydroxypregna-4,16-diene-3,20- dione, C21H28O4, Mr = 344.45, orthorhombic, P212121, a = 7.136 (1), b = 12.342 (1), c = 20.049 (3)Å, V= 1765.7 (3)Å3, Z = 4, Dx = 1.295 g cm-3, λ(Cu Kα) = 1.5418Å, μ = 6.7 cm-1, F(000) = 744, T = 293 K, R = 0.048 for 1345 observations. The A ring may be described as in a l α,2β- half-chair conformation or a l α-sofa conformation. The B and C rings adopt normal chair conformations and the D ring has a 14α-envelope conformation. The molecules are held together by a hydrogen bond [O(3)...O(7)= 2.767 Å]

Structure of a steriod fungal metabolite

3α,7 α, 14 α -Trihydroxypregn-16-en-20-one, C21H3204, Mr = 348.48, orthorhombic, P212121, a = 9.211 (1), b = 13.201 (1), c = 16.031 (1) Å, V = 1949.28 (29) Å3, Z = 4, Dx = 1.187 g cm-3, λ(Cu Kα), = 1.5418 Å, μ = 6.07 cm-1, F(000) = 760, T= 293 K, R = 0.061 for 1337 observations. The A, B and C rings adopt normal chair conformations with the D ring in a 14α-envelope conformation. The molecules are held together by two hydrogen bonds [O(3)…O(20) = 2.879 and O(7)…O(14) = 2.612 Å]

Structure of 9α,19-dihydroxy-4-androstene-3,17-dione

C19H26O4, M1 = 318.41, orthorhombic, P212121, a = 10.591 (1), b = 11.133 (1), c = 13.657 (2) Å, V – 1610.29 Å3, Z = 4, Dm (flotation in KI) = 1.301, Dx = 1.313 g cm-3, Mo Kα, Å = 0.7107 Å, μ = 0.85 cm-1, F(000) = 688, T = 293 K, R – 0.057 for 1253 significant reflections. The Å ring is disordered with atoms C(2) and O(19) occupying two possible sites. The molecules are held together by a hydrogen bond [O(9)…O(17) = 2.89 Å]