Oxidative metabolic detoxification

Rhodanese is widely distributed in the body, but activity levels in mammals are highest in the mitochondrial fraction of liver. Rhodanese activity levels in catalyzing the transformation of thiosulfate to thiocyanate are limited by the availability of sulfur. Minor detoxification pathways for cyanide include exhalation in breath as HCN, and as C02 from oxidative metabolism of formic... 

In other weed biotypes, resistance to triazine herbicides is likely conferred by rapid metabolism of the herbicides to inactive compounds. A chlorotoluron-resistant biotype of blackgrass (slender foxtail) was cross-resistant to various other groups of herbicides, including triazines (Kemp et al., 1990). The mechanism of chlorotoluron resistance was Cyt P450-based enhanced oxidative metabolism through /V-demethylation and ring-methyl hydroxylation (Moss and Cussans, 1991). Consequently, it is likely that resistance to triazines in this blackgrass biotype is also due to enhanced herbicide detoxification. 

Biotransformation involves oxidation via the cytochrome P450 system and subsequent detoxification by conjugation with glutathione and cellular macromolecules. The oxidative metabolic pathway is saturable, occurring at an oral dose of 10-50 mg kg in the rat, and at inhalation exposures exceeding 200 ppm. Elimination of vinylidene chloride and its metabolites occurs primarily through the urine and in the expired air at a relatively rapid excretion rate. 

Shangari N et al., Toxicity of glyoxals-role of oxidative stress, metabolic detoxification and thiamine deficiency, Biochem. Soc. Trans., 31, 1390, 2003. 

Detoxification of organophosphorus pesticides before they can reach their target sites is probably the main reason for poor correlation between carcinogenicity and electrophilicity/mutagenicity. The problem is further complicated by the fact that several different enzymes are involved in the metabolic detoxification of organophosphorus pesticides. For example, paraoxon, tetrachlojTvinphos and dimethoate are preferentially detoxified by A-esterase (paraoxonase), GSH-dependent S-alkyltransferase and carboxyesterase (aliesterase), respectively whereas chlorfenvinphos is mainly detoxified by NADPH-dependent oxidative dealkylation... 

The metabolism of MBOCA was also investigated in vitro by incubating human and rat liver microsomes with C-MBOCA. The formation of metabolites was quantified using appropriate chemically synthesized standards (Morton et al. 1988). The rate of N-hydroxylation of MBOCA, an obligatory step in metabolic activation of aromatic amines, was higher in rat than in human microsomes (Morton et al. 1988). Rat liver microsomes were also found to be more efficient in o-hydroxy-MBOCA formation when compared with human microsomes (see Figure 2-2). The same in vitro microsomal system was used to elucidate the role of hepatic cytochrome P-450 monooxygenases in metabolic oxidation and detoxification of MBOCA (Butler et al. 1989). The... 

FIGURE 2-4. Proposed Metabolic Pathway of 1,1,2-Trichloroethane. a) one-electron oxidation b) two-electron oxidation c) detoxification step.—supposed pathway -proven pathway... 

The basis of selectivity of foramsulfuron in the presence of the safener isoxadifen-ethyl is a more rapid rate of metabolic detoxification in maize compared with target weeds, in which little or no degradation of the parent sulfonylurea occurs [51]. Three main routes of metabolism have been established in maize - a hydrolytic cleavage of the sulfonylurea bridge, a deformylation of the amino group and oxidative metabolism of the dimethoxypyrimidine ring. 

While the available data suggest oxidative metabolism as the main route for detoxification of at least two of the four bisacylhydrazine insecticides (tebufenozide and methoxyfenozide), there has not been any evidence of target site resistance. 

Reactive carbonyls are formed as a normal part of oxidative metabolism The production and accumulation are enhanced in diabetes, due to a combination of chronic hyperglycemia and oxidative stress where they play a significant role in the development and progression of diabetic complications Increased accumulation of toxic carbonyls is also believed to play a role in a number of other conditionsMost research has focused on the enzymatic detoxification pathways of toxic carbonyls However, less attention has been paid to the excretion of carbonyls in the urine. 

Aposhian, H.V., Zakharyan, R.A., Avram, M.D., et al, 2003. Oxidation and detoxification of trivalent arsenic species. Toxicol. Appl. Pharmacol. 193,1-8. Apostoli, P, Alessio, L., Romeo, L., et al., 1997. Metabolism of arsenic after acute occupational arsine intoxication. J. Toxicol. Environ. Health 52, 331-342. ATSDR, 2000. Toxicological Profile for Arsenic (Update). US Department of Health and Human Services, US Government Printing Office, USA. Bartelt-Hunt, S.L., Barlaz, M.A., Knappe, D.R.U., et al., 2006. Fate of chemical warfare agents and toxic industrial chemicals in landfills. Environ. Sd. Technol. 40, 4219-4225. 

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