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At least 19 recordsLinked to original sources

PubMed1979

Failure of rotenone to interfere with 17 beta-estradiol action in the rat uterus.

The involvement of rotenone in rat mammary carcinogenesis has been suggested to occur through estrogenic effects. This hypothesis was tested by determining the extent of rotenone inhibition of 17 beta-estradiol binding to the estrogen receptor and of the 17 beta-estradiol-induced uterotrophic response in ovariectomized Sprague-Dawley rats. Estradiol binding to the uterine estrogen receptor in the presence of rotenone was determined by charcoal assay and Scatchard analysis. Additionally, 17 beta-estradiol-receptor interactions were assessed on sucrose density gradients. No inhibition of binding was observed in either assay with ratios of rotenone/17 beta-estradiol in excess of 10,000. Finally, an in vivo approach was used to extend the in vitro data. Silastic capsules containing rotenone or 17 beta-estradiol were implanted in various combinations into eight groups of ovariectomized Sprague-Dawley rats (four rats/group). After five days, uteri were removed and weighed. An analysis of variance revealed that rotenone neither interfered with 17 beta-estradiol-induced uterine weight gain nor displayed any uterotrophic properties by itself. Results from these three procedures demonstrate that rotenone does not act as an estrogen or as an estrogen antagonist. Additionally, there were no other effects attributable to rotenone.

Animals↗

PubMed1991

Succinate-driven reverse electron transport in the respiratory chain of plant mitochondria. The effects of rotenone and adenylates in relation to malate and oxaloacetate metabolism.

The effects of rotenone on the succinate-driven reduction of matrix nicotinamide nucleotides were investigated in Percoll-purified mitochondria from potato (Solanum tuberosum) tubers. Depending on the presence of ADP or ATP, rotenone caused an increase or a decrease in the level of reduction of the matrix nicotinamide nucleotides. The increase in the reduction induced by rotenone in the presence of ADP was linked to the oxidation of the malate resulting from the oxidation of succinate. Depending on the experimental conditions, malic enzyme (at pH 6.6 or in the presence of added CoA) or malate dehydrogenase (at pH 7.9) were involved in this oxidation. At pH 7.9, the oxaloacetate produced progressively inhibited the succinate dehydrogenase. In the presence of ATP the production of oxaloacetate was stopped, and succinate dehydrogenase was protected from inhibition by oxaloacetate. However, previously accumulated oxaloacetate transitorily decreased the level of the reduction of the NAD+ driven by succinate, by causing the reversal of the malate dehydrogenase reaction. Under these conditions (i.e. presence of ATP), rotenone strongly inhibited the reduction of NAD+ by succinate-driven reverse electron flow. No evidence for an active reverse electron transport through a rotenone-insensitive path could be obtained. The inhibitory effect of rotenone was masked if malate had previously accumulated, owing to the malate-oxidizing enzymes which reduced part or all of the matrix NAD+.

Adenosine Diphosphate↗

PubMed1990

The measurement of the rotenone-sensitive NADH cytochrome c reductase activity in mitochondria isolated from minute amount of human skeletal muscle.

Mitochondria isolated from minute amounts (100-500 mg) of human skeletal muscle displayed a very high rotenone-resistant NADH cytochrome c reductase activity. Moreover, compared to succinate cytochrome c reductase activity, a low rate of rotenone-sensitive NADH cytochrome c reductase activity was measured when using standard procedures to disrupt mitochondrial membranes. Only a drastic osmotic shock in distillated water as a mean to disrupt mitochondrial membrane was found to strongly increase the actual rate of the rotenone-sensitive activity. This was accompanied by a decrease in the rotenone-insensitive activity. Using such a simple procedure, the NADH cytochrome c reductase was found 70-80% inhibited by rotenone and roughly equivalent to 70-85% of the activity of the succinate cytochrome c reductase.

Cell Fractionation↗

PubMed1976

Action of rotenone and related respiratory inhibitors on mammalian cell division. 1 Cell kinetics and biochemical aspects.

Inhibitors of mitochondrial respiration, phosphorylation inhibitors, and uncoupling agents have been reported to delay or inhibit mitosis in cultured mammalian cells. Although the molecular mechanism by which mitosis is delayed in the presence of most respiratory inhibitors presumably involves lowered ATP production for mitotic requirements, one respiratory inhibitor, rotenone, was determined to arrest mitosis by an unrelated mechanism. Cell cycle kinetics studies, oxygen consumption measurements, and viscosity assays indicate that rotenone arrests cultured mammalian cells in mitosis by inhibiting spindle microtubule assembly by a mechanism analogous with colchicine, Colecemid and related antimitotic drugs. Amytal, which blocks electron transport at the same site as does rotenone, failed to arrest cell progression at mitosis. Rotenone delayed cell progression in all phases of the cell cycle, apparently as a direct result of respiration inhibition. Thus, rotenone appears to exert a dual function on events of the cell cycle.

Amobarbital↗

PubMed1978

High pressure liquid chromatographic determination of rotenone and degradation products in animal chow and tissues.

An analytical procedure is described for determining residues of rotenone, rotenolone, dehydrotenone, and rotenone in admixture in animal chow and tissues. The methanol or ethyl ether extracts from samples of chow and tissues, respectively, are subjected to a liquid-liquid partitioning cleanup with hexane-acetonitrile, further cleanup on a column of silica gel, and subsequent analysis by high pressure liquid chromatography using an ultraviolet absorption detector set at 295 nm. Animal chow, mouse fetuses, and gastrointestinal tracts spiked with 0.5 ppm of each compound in admixture yielded average recoveries of 92, 51, and 79%, respectively; minimum quantities of the 4 compounds detectable in the 3 substrates averaged 0.12, 0.04, ajd 0.14 ppm, respectively. Stability studies indicate that rotenone reacts with animal chow with a half-life of 7--8 days and is photodegraded in incandescent light with a half-life of 0.65 day. No transplacental transfer of rotenone or its products was observed in fetuses from mice receiving 7 consecutive daily doses of rotenone at levels up to 25 mg/kg.

Animal Feed↗

PubMed1992

Sensitive period for the induction of endoreduplication by rotenone in cultured Chinese hamster cells.

Rotenone-induced endoreduplication was investigated in Chinese hamster CHL cells. Cell cycle analyses, using 5-bromo-2'-deoxyuridine (BrdU) labeling, revealed that endoreduplication was induced between the G2-phase and mitotic metaphase. Morphological studies indicated that the chromosomes of cells in metaphase at the time of rotenone exposure immediately aggregated. Within 1 h, however, the aggregated chromosomes began to decondense forming telophase nuclei. Cells with aggregated chromosomes were collected by mitotic selection using the mitotic arrestant TN-16 and then cultured for 30 h following rotenone administration. This population of cells demonstrated an extremely high frequency of endoreduplicated metaphases. Further analysis by BrdU labeling indicated that the aggregated metaphases underwent only one round of DNA replication before endoreduplicated metaphases were formed. The most sensitive period for the induction of endoreduplication by rotenone occurs during mitotic metaphase.

Animals↗

PubMed1978

The role of lipid-protein interactions in NADH-cytochrome c reductase (rotenone-insensitive) of rat liver mitochondria.

The phospholipid depletion of rat liver mitochondria, induced by acetoneextraction or by digestion with phospholipase A2 or phospholipase C, greatly inhibited the activity of NADH-cytochrome c reductase (rotenone-insensitive). A great decrease of the reductase activity also occurred in isolated outer mitochondrial membranes after incubation with phospholipase A2. The enzyme activity was almost completely restored by the addition of a mixture of mitochondrial phospholipids to either lipid-deficient mitochondria, or lipid-deficient outer membranes. The individual phospholipids present in the outer mitochondrial membrane induced little or no stimulation of the reductase activity. Egg phosphatidylcholine was the most active phospholipid, but dipalmitoyl phosphatidylcholine was almost ineffective. The lipid depletion of mitochondria resulted in the disappearance of the non-linear Arrhenius plot which characterized the native reductase activity. A non-linear plot almost identical to that of the native enzyme was shown by the enzyme reconstituted with mitochondrial phospholipids. Triton X-100, Tween 80 or sodium deoxycholate induced only a small activation of NADH-cytochrome c reductase (rotenone-insensitive) in lipid-deficient mitochondria. The addition of cholesterol to extracted mitochondrial phospholipids at a 1 : 1 molar ratio inhibited the reactivation of NADH-cytochrome c reductase (rotenone-insensitive) but not the binding of phospholipids to lipid-deficient mitochondria or lipid-deficient outer membranes. These results show that NADH-cytochrome c reductase (rotenone-insensitive) of the outer mitochondrial membrane requires phospholipids for its activity. A mixture of phospholipids accomplishes this requirement better than individual phospholipids or detergents. It also seems that the membrane fluidity may influence the reductase activity.

Animals↗

PubMed1992

The effect of delta mu H+ on the interaction of rotenone with complex I of submitochondrial particles.

The inhibition by rotenone of the forward (NADH-oxidase) and reverse (delta mu H(+)-dependent succinate-NAD+ reductase activities of submitochondrial vesicles was measured. The inhibition of NADH-oxidase, measured in the presence of uncoupler, followed a monophasic inhibition curve with Ki < or = 2 nM. The reverse electron flow was only partially (40%) inhibited at these rotenone concentrations. The rest of the activity was less sensitive to the inhibitor (Ki approximately 30 nM). The lower affinity for the inhibitor of the reverse electron flow is a consequence of enhanced rate of rotenone dissociation caused by the high delta mu H+ value required for this reaction. The analysis of the results indicates that the AS-SMP preparation consists of two subpopulations: one with a relatively low degree of coupling, which exhibits high sensitivity to rotenone and the other which is highly coupled with lower affinity to the inhibitor.

Mitochondria↗

PubMed1990

Evidence that the blockade of mitochondrial respiration by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) involves binding at the same site as the respiratory inhibitor, rotenone.

It has been postulated that 1-methyl-4-phenylpyridinium (MPP+) blocks mitochondrial respiration by combining at the same site as rotenone, a potent inhibitor of NADH oxidation in mitochondria, known to act at the junction of NADH dehydrogenase and coenzyme Q (CoQ). The present experiments show that MPP+ and two of its analogs indeed act in a concentration dependent manner to prevent the binding of [14C]-rotenone to submitochondrial particles (ETP) and significantly decrease the inhibition of electron transport caused by rotenone. It therefore appears that MPP+ binds at the same site as rotenone or an adjacent site, supporting the hypothesis that its neurotoxic action is due to the inhibition of mitochondrial respiration.

1-Methyl-4-phenylpyridinium↗

PubMed1975

Separation of rotenoids and the determination of rotenone in pesticide formulations by high-performance liquid chromatography.

The rotenoids deguelin, B-dihydrorotenone, dehydrorotenone, rotenone, 6alpha beta, 12alpha beta-rotenolone, and tephrosin were chromatographed on 8-12 mum silica. A mobile phase of chloroform-isooctane (35+65) pumped at a flow rate of 1 ml/min through a 30 cm column was used and the absorbance of the eluate was monitored at 294 nm. Rotenone, B-dihydrorotenone, deguelin, and dehydrorotenone are completely resolved while 6alpha beta, 12alpha beta-rotenolone and tephrosin chromatograph as one peak. This method has potential as a preparative separation technique for rotenoids. Also described is a procedure to quantitatively measure rotenone in pesticide formulations. Samples were extracted with chloroform and chromatographed at a flow of 2.5 ml/min. The method is rapid (rotenone is eluted in 12 min) and reproducible.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

A review of the literature of rotenone, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-1-benzopyrano[3,5-b]furo[2,3-h][1]benzopyran-6(6h)-one.

The chemistry, biotransformation, pharmacology, toxicology, and carcinogenicity of rotenone have been reviewed. Further investigation of the biotransformation pathways of rotenone and other rotenoids should be undertaken. The acute and chronic toxicology, particularly at low concentration, should be determined in order to develop toxicity rating for this class of chemicals. A mutagenic study utilizing all presently available methods would add further knowledge concerning sites of action. More information is required to properly evaluate the hazards to humans from rotenone and other rotenoids. Carcinogenic studies at low concentrations with large groups of rodents must be undertaken to settle the present dilemma of carcinogenicity vs. non-carcinogenicity. Moreover, an epidemiological study of exposed workers might develop information concerning the toxicology of rotenone as well as its possible carcinogenicity to humans.

Animals↗

PubMed1992

The non-equivalence of binding sites of coenzyme quinone and rotenone in mitochondrial NADH-CoQ reductase.

The fluorescent probe erythrosine 5'-iodoacetamide (ER) binds to mitochondrial NADH-CoQ reductase (Complex-I) accompanied by an enhancement of the fluorescence intensity. The binding of the CoQ analogue, 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone (DB), decreased the fluorescence intensity of the ER:Complex-I system. The 'site 1' inhibitor rotenone did not decrease the fluorescence intensity showing the non-identical nature of the binding sites of DB and rotenone. Also, the reduced form of DB did not decrease the fluorescence intensity. The decrease of the fluorescence intensity by DB was shown to be due to the removal of bound ER by DB. The rapid kinetics of ER binding was studied by temperature-jump relaxation. While DB caused complete elimination of the relaxation process in the ER:Complex-I system, rotenone caused only a decrease in the relaxation rate, suggesting conformational change. The relaxation rate showed a pH dependence with a maximum around pH 7.5.

Binding Sites↗

PubMed1991

Rotenone induces aneuploidy, polyploidy and endoreduplication in cultured Chinese hamster cells.

The clastogenic potential of rotenone, an insecticide, was investigated in cultured Chinese hamster cells. Rotenone induced aneuploidy (hypodiploidy and hyperdiploidy), polyploidy, and endoreduplication, but not structural chromosome aberrations. The highest frequency of polyploidy and endoreduplication was 58.8% and 3.0%, respectively, when cells were treated with rotenone at 1.0 microgram/ml for 30 h.

Aneuploidy↗

PubMed1978

Rotenone inhibition of tubulin self-assembly.

Rotenone effectively inhibits the in vitro formation of microtubules from tubulin containing or lacking microtubule-associated proteins. In both cases a concentration of rotenone equal to that of tubulin present completely blocks assembly. The inhibition can be reversed by the addition of dimethylsulfoxide or by removing rotenone with charcoal.

Animals↗

PubMed1977

Spectral and metabolic characteristics of mitochondrial fractions from rotenone-induced tumours.

Mitochondrial fractions isolated from tumours induced with the respiratory inhibitor rotenone lack respiratory control, oxidative phosphorylation, are partially or totally insensitive to cyanide and have a near-normal content of respiratory carriers. These characteristics are more similar to those of mitochondria from atrophic mammary gland than to those of mitochondria from spontaneous mammary adenomas. Thus, the characteristic structural and biochemical mitochondrial alteration of rotenone-induced tumours would represent a lack of mitochondrial differentiation as the tumour develops from the atrophic mammary gland. Slices of rotenone-induced tumours are insensitive to oligomycin and dinitrophenol, thus indicating that glycolysis would be their sole source of metabolic energy.

Adenofibroma↗

PubMed1976

Action of rotenone and related respiratory inhibitors on mammalian cell division. 2 Ultrastructural studies.

Light and electron microscopic examination of cultured mammalian cells treated with the respiratory inhibitor rotenone revealed that chromosome, spindle, and centriole configurations were virtually identical to that of mitotic cells arrested with Colcemid, a microtubule assembly inhibitor. The chromosomes of cells arrested in mitosis with either drug were grouped in a spherical mass near the cell centre and centrioles failed to opposite mitotic poles. Spindle microtubules were observed in limited numbers near some chromosome kinetochores and the centrioles. The outer portions of the cell cytoplasm were devoid of microtubules. Scanning and transmission electron microscopy revealed that cells did not progress beyond early stages of mitosis in the presence of rotenone or Colcemid. The ultrastructure of cells harvested from cultures grown in amytal was similar to that of untreated cells. These observations suggest that rotenone arrests mitosis in mammalian cells by inhibition of spindle microtubule assembly.

Amobarbital↗

PubMed1977

Inhibition of hamster sperm acrosome reaction and fertilization by oligomycin, antimycin A, and rotenone.

Effects of respiratory inhibitors (oligomycin, antimycin A and rotenone) on hamster sperm acrosome reaction and fertilization were studied. Hamster spermatozoa were incubated in a mixture of a modified Tyrode's solution and heat-treated human serum in the presence and absence of inhibitors. Oligomycin (2.4 x 10(-6) M), antimycin A (2.5 x 10(-6) M) and rotenone (2.5 x 10(-6) M) all reduced the incidence of the sperm acrosome reaction and fertilization without markedly affecting sperm motility. Antimycin A was the most effective in reducing the incidence of acrosome reaction. A reduction in the rate of fertilization was found in the presence of all of these respiratory inhibitors. The reduction in the incidence of acrosome reaction and fertilization by respiratory inhibitors implies an intimate relationship between high energy production (via respiration and oxidative phosphorylation) and capacitation and the acrosome reaction of spermatozoa. The necessity of oxidative metabolism for efficient capacitation and acrosome reaction of spermatozoa is suggested.

Acrosome↗

PubMed1992

Relation of superoxide generation and lipid peroxidation to the inhibition of NADH-Q oxidoreductase by rotenone, piericidin A, and MPP+.

The addition of NADH to submitochondrial particles inhibited by agents which interrupt electron transport from NADH-Q oxidoreductase (Complex I) to Q10 (rotenone, piericidin A, and MPP+) results in superoxide formation and lipid peroxidation. A study of the quantitative relations now shows that oxyradical formation does not appear to be the direct result of the inhibition. Although tetraphenyl boron (TPB) greatly enhances the inhibition by MPP+, it has no effect on O2. formation or lipid peroxidation. When submitochondrial particles completely inhibited by rotenone or piericidin A are treated with bovine serum albumin to remove spuriously bound inhibitor molecules without affecting those bound at the specific inhibition site, NADH-Q activity remains inhibited and lipid peroxidation occurs but superoxide formation ceases. Thus oxyradical formation may be the result of the binding of inhibitors at sites in the membrane other than those related to the inhibition of electron transport.

1-Methyl-4-phenylpyridinium↗