Disease relevance of PARAQUAT

• Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) was used as an intracellular generator of oxygen free radicals and was found to be highly mutagenic for Salmonella typhimurium [1].
• It is suggested that acute pulmonary oedema is a response to large doses, usually of Gramoxone, that subclinical lung changes result from small doses, usually of Weedol, and that pulmonary fibrosis occurs after intermediate doses [2].
• All dogs given a lethal dose of paraquat dichloride producing 100% mortality as a 2-hr infusion (7.48 mg of paraquat ion per kg) developed the typical clinical, laboratory and pathologic features of paraquat toxicity and died within 5 to 7 days [3].
• Mice treated with Escherichia coli endotoxin (500 micrograms/kg i.p.) 24 and 1 hr before paraquat dichloride (50 mg/kg i.p.) had a 2-fold increase in 7-day cumulative mortality compared to those injected with buffered saline before paraquat [4].
• Sixteen additional rabbits were given paraquat dichloride (25 mg/kg of body weight) intraperitoneally, subcutaneously, intravenously, or orally [5].

High impact information on PARAQUAT

• There is a very highly conserved sequence over 100 basepairs (bp) in length within the intergenic region upstream of the methyl-viologen hydrogenase encoding genes in several different strains of Methanobacterium thermoautotrophicum, indicating that a sequence of this length is needed to direct and regulate the expression of these genes [6].
• Consistent with nuclear run-off assays, transient transfection experiments using a series of pGL2-derived luciferase reporter plasmids containing the human apoAI proximal promoter demonstrated that gramoxone treatment increased apoA-I promoter activity 2-fold [7].
• These studies revealed a 4-fold increase in the rate of apoA-I mRNA degradation in cells exposed to gramoxone [7].
• Regulation of human apolipoprotein A-I gene expression by gramoxone [7].
• To examine if increased rates of mRNA degradation were responsible for the reduction in apoA-I mRNA levels, mRNA half-lives were measured in the presence of actinomycin D with and without gramoxone treatment [7].

Chemical compound and disease context of PARAQUAT

• E. coli B strains with different DNA-repair capacities were exposed to methyl viologen, commonly called paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride, MV), which has been shown to act as an intracellular generator of superoxide radicals [8].
• Previously, it has been shown that treatment of Paracoccus denitrificans cells with phenylglyoxal inhibits the methyl-viologen-linked nitrate reductase activity by blocking the nitrate transporter [9].
• Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or alpha-tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats were killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment [10].
• The study revealed that high molecular polyvinyl sulfate (PVP) or sulfonate (PVS), and low molecular alkyldisulfonates (NaO3S(CH2)nSO3Na, n = 2--5: EDS, TDS, BDS and PDS) can alleviate acute toxicity of the herbicide, paraquat dichloride (PQ) in mice [11].

Biological context of PARAQUAT

• In contrast, a plasmid containing a mutant apoAI-ARE did not confer responsiveness to gramoxone [7].
• To induce oxidative stress, HepG2 cells were exposed to a compound known as gramoxone [7].
• Furthermore, pGL2 (apoAI-250 mutant ARE), in which point mutations eliminated the ARE in the apoAI promoter, showed no increase in luciferase activity in response to gramoxone [7].
• We have identified a potential "antioxidant response element" (ARE) in the apoA-I promoter region that may be responsible for the increase in apoA-I transcriptional activity by gramoxone [7].
• At the gene mutation level Gramoxone induced gene conversion at the trp-5 locus and reversion at the ilv locus in Saccharomyces cerevisiae [12].

Anatomical context of PARAQUAT

• The results indicate that Gramoxone has mutagenic activity at the cytological level in Allium cepa, Vicia faba and human lymphocytes [12].
• In Drosophila melanogaster, Gramoxone proved to be mutagenic to germ cells and induced a high frequency of sex-linked recessive lethals (SLRL) [12].
• One picogram of paraquat dichloride delivered by bronchial catheter produced a 1.0-mm pulmonary lesion consisting of focal hemorrhage, congestion of capillaries, intra-alveolar macrophages, and moderate thickening of the alveolar septa [5].
• The intraperitoneal injection of paraquat dichloride resulted in time- and dose-dependent decreases in angiotensin converting enzyme and alkaline phosphatase activities suggesting that the toxicant injures both the capillary endothelial cells and alveolar type II epithelial cells, respectively [13].
• In three cases of intoxication by Gramoxone¿, the concentration of paraquat dichloride in blood, dialysate, feces, and urine was determined spectrophotometrically after a clean-up of the biological material by means of ion exchange chromatography (with Dowex 50W-X12 or Zeo-Karb 225) [14].

Associations of PARAQUAT with other chemical compounds

• The pulse radiolysis of ART in H(2)O/ethanol (EtOH) (1:1 v/v) solution was studied in the absence and presence of the so-called redox indicators N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), Fe(CN)6(4-), 1,1'-dimethyl-4,4'-bipyridinium dichloride (methyl viologen, MV(2+)) and Fe(CN)6(3-) [15].
• In rats fed a tungsten-enriched diet for 5 weeks prior to intraperitoneal injection of 50 mg/kg paraquat dichloride, the mortality decreased significantly compared with rats fed a standard diet [16].
• In this study the pH-dependent interactions interactions between a paraquat-specific murine monoclonal antibody and two antigens: paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride), and a p-nitrophenol analogue (1-(N-methyl-4,4'-bipyridinium)-1-(2-hydroxy-5-nitrophenyl)methane dichloride; PQNP) were determined by ELISA [17].
• Biological studies were done using the eukaryotic cells of superoxide-dismutase proficient and deficient strains of Saccharomyces cerevisiae treated with hesperidin and the stressing agents hydrogen peroxide or paraquat (methylviologen; 1,1'-dimethyl-4,4'-bipyridinium dichloride) [18].
• Environmental stress and parasitic infections: II. Effects of gramoxone and hexadrin (pesticides) on the survival characteristics of Fasciola gigantica miracidia [19].

Gene context of PARAQUAT

• A 2.8 kb acnA monocistronic transcript was detected by Northern blot hybridization, but only in redox-stressed (methyl-viologen-treated) cultures, and a 2.5 kb acnB monocistronic transcript was detected in exponential- but not stationary-phase cultures [20].
• The possible mutagenicity of the herbicide Gramoxone was evaluated using five different living systems: Allium cepa, Vicia faba, yeast, Drosophila melanogaster and human lymphocytes [12].
• At the protein level, Gramoxone had detectable mutagenic effects on the genetic background of two enzymes, Adh and Est-6 [12].
• Accidental or intentional ingestion of Gramoxone has caused 232 human deaths between 1964 and 1973 (Anon 1974) [21].
• Effects of Gramoxone and cooling on the antioxidant enzymes of frog (Rana esculenta) [22].

Analytical, diagnostic and therapeutic context of PARAQUAT

• Gel mobility shift assays with an ARE oligonucleotide revealed increased levels of a specific protein-DNA complex that formed with nuclear extracts from gramoxone-treated cells [7].
• In this study, we have used BAL to detect early pulmonary injury in beagle dogs following an intravenous infusion of 10 mg paraquat dichloride/kg bodyweight [23].
• A simple, sensitive, reliable, and economical method for simultaneous determination of paraquat dichloride and diquat dibromide in human biological materials has been developed, using high-performance liquid chromatography [24].
• The reported findings indicate that: only 5 to 10% of an ingested dose of paraquat dichloride is absorbed in man, Fullers' earth is very useful, and that primary, e.g. immediate, hemodialysis is necessary [14].
• Within 6-12 hr a single intravenous injection of 40 mg/kg paraquat dichloride caused selective mitochondrial swelling and loss of intramitochondrial granules within 24 hr in alveolar Type II cells [25].

References