Clomazone: Toxicity, Biotransformation, Resistance and Interaction with P450 Inhibitors in Rice (Oryza sativa) and Watergrasses (Echinochloa spp.)

Rice (Oryza sativa), early watergrass (Echinochloa oryzoides); EWG; biotypes resistant (R) and susceptible (S) to thiocarbamates and aryloxyphenoxy propionate herbicides), and late watergrass (Echinochloa phyllopogon; LWG; R and S biotypes) were exposed to clomazone for 7 d. Whole-plant change in fresh weight and B-carotene concentrations were measured. For growth, the No Observed Effect Concentrations (NOECs) were 7.9, 0.21, 0.21, 0.46, and 0.46 µM clomazone for rice, EWG (R), EWG (S), LWG (R), and LWG (S), respectively, while the concentrations causing 25% inhibition in response (IC25s) were 5.6, 0.46, 0.42, 0.92 and 0.79 µM clomazone, respectively. For rice, EWG (R), EWG (S), LWG (R), and LWG (S), the B-carotene NOECs were 0.21, < 0.08, < 0.08, 0.08 and 0.46 µM clomazone, respectively and IC25s were 0.42, 0.08, 0.08, 0.33 and 0.54 µM, respectively. At a field-relevant clomazone application rate resistance to clomazone was observed in EWG (R) and LWG (R) as measured by growth and B-carotene, respectively. Due to similar sensitivity between rice and late watergrass, use of clomazone in rice culture may require the use of a safening technique.Rice and EWG (S) were exposed to 14C-labeled clomazone to determine accumulation, biotransformation and mass balance. In terms of extractable 14C, rice contained more total residues than EWG (p < 0.05), but the concentration in EWG was significantly higher (p < 0.01). More metabolized residue was measured in EWG compared to rice (p < 0.01). Both species produced hydroxylated forms of clomazone, B-D-glucoside conjugates, and unidentified polar metabolites. The suspected active metabolite, 5-ketoclomazone, was found at a significantly higher concentration in EWG vs. rice (21 ± 2 vs. 5.7 ± 0.5 pmol g-1, respectively; p < 0.01). Qualitatively and quantitatively, more clomazone metabolism was observed in the relatively sensitive EWG compared to rice.R and S biotypes of EWG and LWG were exposed to clomazone alone and in combination with P450 inhibitors. Growth reduction (GR25, GR50, and GR75) values were lower for S biotypes than for R biotypes (p < 0.05) with exposure to clomazone alone indicating resistance to clomazone in the R biotypes. In combination with clomazone disulfoton increased 20-d growth in LWG (R) by as much as 5-fold, compared to application of clomazone alone. Oxydemeton methyl increased 20-d growth by as much as 6-fold. Disulfoton and oxydemeton methyl reduced !)-carotene levels compared to treatment with clomazone alone. For EWG (S), disulfoton increased 4-d growth by 46% and increased B-carotene levels by 52%. Demeton-S increased B-carotene levels by 48%. At 6800 g ai ha-1 PBO increased growth and B-carotene levels by 28 and 48%, respectively. These results indicate that P450 enzymes serve both to activate and detoxify clomazone

Clomazone: Toxicity, Biotransformation, Resistance and Interaction with P450 Inhibitors in Rice (Oryza sativa) and Watergrasses (Echinochloa spp.)

Rice (Oryza sativa), early watergrass (Echinochloa oryzoides); EWG; biotypes resistant (R) and susceptible (S) to thiocarbamates and aryloxyphenoxy propionate herbicides), and late watergrass (Echinochloa phyllopogon; LWG; R and S biotypes) were exposed to clomazone for 7 d. Whole-plant change in fresh weight and B-carotene concentrations were measured. For growth, the No Observed Effect Concentrations (NOECs) were 7.9, 0.21, 0.21, 0.46, and 0.46 µM clomazone for rice, EWG (R), EWG (S), LWG (R), and LWG (S), respectively, while the concentrations causing 25% inhibition in response (IC25s) were 5.6, 0.46, 0.42, 0.92 and 0.79 µM clomazone, respectively. For rice, EWG (R), EWG (S), LWG (R), and LWG (S), the B-carotene NOECs were 0.21, < 0.08, < 0.08, 0.08 and 0.46 µM clomazone, respectively and IC25s were 0.42, 0.08, 0.08, 0.33 and 0.54 µM, respectively. At a field-relevant clomazone application rate resistance to clomazone was observed in EWG (R) and LWG (R) as measured by growth and B-carotene, respectively. Due to similar sensitivity between rice and late watergrass, use of clomazone in rice culture may require the use of a safening technique.Rice and EWG (S) were exposed to 14C-labeled clomazone to determine accumulation, biotransformation and mass balance. In terms of extractable 14C, rice contained more total residues than EWG (p < 0.05), but the concentration in EWG was significantly higher (p < 0.01). More metabolized residue was measured in EWG compared to rice (p < 0.01). Both species produced hydroxylated forms of clomazone, B-D-glucoside conjugates, and unidentified polar metabolites. The suspected active metabolite, 5-ketoclomazone, was found at a significantly higher concentration in EWG vs. rice (21 ± 2 vs. 5.7 ± 0.5 pmol g-1, respectively; p < 0.01). Qualitatively and quantitatively, more clomazone metabolism was observed in the relatively sensitive EWG compared to rice.R and S biotypes of EWG and LWG were exposed to clomazone alone and in combination with P450 inhibitors. Growth reduction (GR25, GR50, and GR75) values were lower for S biotypes than for R biotypes (p < 0.05) with exposure to clomazone alone indicating resistance to clomazone in the R biotypes. In combination with clomazone disulfoton increased 20-d growth in LWG (R) by as much as 5-fold, compared to application of clomazone alone. Oxydemeton methyl increased 20-d growth by as much as 6-fold. Disulfoton and oxydemeton methyl reduced !)-carotene levels compared to treatment with clomazone alone. For EWG (S), disulfoton increased 4-d growth by 46% and increased B-carotene levels by 52%. Demeton-S increased B-carotene levels by 48%. At 6800 g ai ha-1 PBO increased growth and B-carotene levels by 28 and 48%, respectively. These results indicate that P450 enzymes serve both to activate and detoxify clomazone

Influence of gene polymorphisms in ulcer healing process after superficial venous surgery

OBJECTIVE: Role of superficial venous surgery in reducing the time it takes for ulcers to heal is still controversial, although all studies confirm a significant reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene variants demonstrated a role in the risk of venous ulceration in primary chronic venous disorder (CVD) and in modulating lesion size in chronic venous ulcer (CVU), respectively. This study was conducted to investigate the role of HFE-C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after superficial venous surgery, by assessing the outcome of a cohort of homogeneous CVU patients. METHODS: The study selected 91 patients affected by primary CVU (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor involved in delayed healing process, who underwent surgery. We assessed the ulcer area and the healing time. Patients were genotyped by polymerase chain reaction for FXIII (V34L and P564L) and for HFE-C282Y substitutions. RESULTS: Globally, CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L genotype distribution significantly differed (P < .0001). In addition, Kaplan-Meier analysis yielded specific healing time profiles for the different FXIII-V34L classes of genotype (P = .00001), with an increased risk of delayed healing for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to 8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ, homozygous 564LL cases (P = .005) and double carriers for both FXIII variants (P < .0001), had a significantly reduced healing time vs wild types. No differences in healing time were observed between carriers and noncarriers of the HFE-C282Y variant, whereas when these cases were stratified by FXIII-V34L genotypes, the L34 carriers had a significantly shorter healing time, irrespective of the HFE genotype. CONCLUSION: The FXIII-34L variant was significantly associated with shorter healing time after superficial venous surgery, suggesting a role in the healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role in ulcer establishment, did not affect the postoperative healing time. In perspective, the identification of patients with a poor prognosis may give clinicians the opportunity to modify management and to target tailored therapies in the view of a new and alternative concept of treatment based on pharmacogenomics