The mechanism of bentazon selectivity

Absorption, translocation and metabolism of [¹⁴C]3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide (bentazon) by several plant species were investigated to determine the mechanism of bentazon selectivity.Marked selective phytotoxicities were observed between resistant rice (Oryza sativa L.) and susceptible Cyperus serotinus Rottb. when treated with bentazon. Absorption and transolcation of bentazon did not differ greatly between highly resistant rice and susceptible C. serotinus. However, a marked difference in bentazon metabolism occurred between the two species. In rice about 80% of the absorbed bentazon was metabolized within 24 h, and after 7 days about 85% was converted to a major water-soluble metabolite and unchanged bentazon was only 5%. In C. serotinus 50–75% of the radioactivity was unchanged bentazon after 7 days.Large amounts of water-soluble metabolites were detected in root-treated resistant plants such as barnyardgrass (Echinochloa crus-galli Beauv.), soybean (Glycine max Merr.) and corn (Zea mays L.), but only small amounts were present in such susceptible plants as Sagittaria pygmaea Miq. and Eleocharis kuroguwai Ohwi. Therefore, the mechanism of bentazon selectivity appears to be a difference between resistant and susceptible species in their ability to metabolize and detoxify bentazon.The major metabolite in rice was identified as 6-(3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide)-O-β-glucopyranoside, determined by GC-MS, NMR, IR and gas chromatography after hydrolysis with sulfuric acid or β-glucosidase.     

Cytomorphological and immunohistochemical features of lymphoma in ferrets

Twenty ferrets with histopathologically diagnosed lymphoma were classified cytomorphologically and immunohistochemically. According to site of origin, multicentric, gastrointestinal, mediastinal and cutaneous lymphomas accounted for 8 (40%), 9 (45%), 2 (10%) and 1 case (5%), respectively. According to the National Cancer Institute Working Formulation (NCI-WF), low-, high- and intermediate-grade lymphomas accounted for 4 (20%), 4 (20%) and 12 cases (60%), respectively. The 4 low-grade lymphomas showed no mitotic figures, whereas all 4 high-grade lymphomas exhibited > or = 3 mitotic figures (median,6). Higher grade thus appears to be associated with a higher number of mitotic figures. Immunohistochemical examination of 18 specimens, excluding 2 insufficient specimens, showed that 16 (88.9%) and 2 (11.1%) lymphomas were of T-cell origin and B-cell origin, respectively. According to the combination of the NCI-WF and immunophenotypes, all 4 low-grade lymphomas (2 multicentric, 1 gastrointestinal, and 1 cutaneous lymphoma) were classified as diffuse small lymphocytic lymphoma of T-cell origin. Of the 12 intermediate-grade lymphomas (6 multicentric, 4 gastrointestinal, and 2 mediastinal lymphomas), 11 were classified as diffuse mixed-cell lymphoma, and 1 as diffuse large cell lymphoma. Of these 11 lymphomas, 2 (both multicentric) were of B-cell origin, 7 (3 multicentric, 3 gastrointestinal, 1 mediastinal) were of T-cell origin, and 2 (1 multicentric, 1 mediastinal) were of unknown cell origin. The remaining 1 lymphoma (gastrointestinal) was of T-cell origin. All 4 high-grade lymphomas (gastrointestinal) were classified as diffuse immunoblastic lymphoma of T-cell origin.     

Plasma concentrations of an angiotensin-converting enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, after repeated administrations of benazepril in dogs with experimental kidney impairment

In order to examine the safety of an angiotensin-converting enzyme (ACE) inhibitor in dogs with impaired renal excretion route, benazepril was administered orally, and plasma concentrations of benazeprilat, the active metabolite of benazepril, were determined in dogs with renal mass reduction (1/4th kidney) created by right-side nephrectomy and ligation of branches of the left renal arteries. Five dogs were administered benazepril orally at a given dose (0.5 mg/kg body weight) and 4 other dogs received 20 times that dose (10 mg/kg body weight) once daily for 15 consecutive days before (intact kidney period) and after (1/4th kidney period) creation of kidney impairment. Six control dogs received surgical treatment, but no drug. After creating a 1/4th kidney, plasma urea nitrogen and creatinine concentrations increased to approximately 30 mg/dl and 2.0 mg/dl, respectively, and renal plasma flow and glomerular filtration rate decreased to 37% and 30% of pre-treatment values, respectively. However, these parameters did not change significantly during the 1/4th kidney period both in the 0.5 mg/kg and 10 mg/kg groups. In the 0.5 mg/kg group, plasma benazeprilat concentrations increased to approximately 20 ng/ml to 340 ng/ml 2 hr after each administration, and there were no significant differences between the plasma benazeprilat concentrations during the intact and 1/4th kidney periods. In the 10 mg/kg group, plasma benazeprilat concentrations varied in the individual dog, but did not increase with the days of administration, and were not significantly different on each administration day between the intact and 1/4th kidney periods in either dose group. The AUCs(0-24) of plasma benazeprilat concentrations determined on the 15th administration day were not different between the intact and 1/4th kidney periods in dogs of either dose group. Plasma ACE activities decreased after drug administration in dogs of both groups. Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver.     

Changes of abscisic acid and its metabolite during development of apple fruit

Summary

Free and conjugated abscisic acid (ABA) and phaseic acid (PA) concentrations in the seed and pulp of apples (Malus pumila Mill. cv. Tsugaru) and ABA metabolism in the fruit after cis-(+)-ABA application were investigated. In the seed, the levels of cis- and trans-ABA and conjugated cis- and trans-ABA showed a general increase towards harvest, except for the decrease of cis-ABA at 131 d after full bloom (DAFB) (harvest). PA levels reached a peak at 41 DAFB, then decreased until harvest. The levels of free ABA in the seed were higher than those in the pulp. In the pulp, the levels of cis-ABA increased gradually from 20 DAFB and rapidly from 111 DAFB towards harvest. The levels of trans-ABA and conjugated trans-ABA also showed similar changes to cis-ABA, i.e. increased steeply from 111 DAFB. In contrast, the level of conjugated cis-ABA was the highest at 20 DAFB, then fell rapidly until 111 DAFB and then increased again towards harvest. PA showed the highest level at 20 DAFB, then decreased gradually until 111 DAFB and then increased again towards harvest. It is therefore assumed that not only cis-ABA but also its metabolite may be associated with the ripening of apple fruit. Cis- and trans-ABA and conjugated cis- and trans-ABA concentrations in cis-(+)-ABA treated fruit increased significantly on 11 d after ABA application (122 DAFB). However, at 20 d after cis-(+)-ABA application, only trans-ABA and conjugated trans-ABA showed higher levels than those of the untreated control, while the levels of cis-ABA and conjugated cis-ABA fell to the same levels as the untreated control. PA levels did not show significant increase on 11 and 20 d after cis-(+)-ABA application. These results suggest that cis-(+)-ABA treated exogenously to apple fruit may eventually metabolize to trans-ABA, conjugated trans-ABA and further metabolites.     

Compounds inhibitory to rat liver 5α-reductase from tropical commercial wood species: resveratrol trimers from melapi (Shorea sp.) heartwood

5-Reductase inhibitory activity of methanol extracts of the heartwood of 13 tropical wood species were examined. Strong 5-reductase inhibitory activity was observed withShorea species. From melapi (Shorea sp.), two known resveratrol trimers, vaticanol A and ampelopsin C, and two novel trimers were isolated as active compounds. The structures of the two novel resveratrol trimers were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopic analyses, including¹H-¹HCOSY, HMQC, and HMBC. The compounds were named melapinol A and melapinol B. There were no significant differences among the 5-reductase inhibitory activities of the four resveratrol trimers, which were significantly stronger than those of-linolenic acid and epigallocatechin gallate, known 5-reductase inhibitors.     

Evaluation of biological activities of extracts from 22 African tropical wood species

Heartwoods of 22 African tropical wood species were extracted with methanol and the contents of total phenolic compounds in these extracts were measured. Three bioassays were conducted to evaluate the antioxidant activity, tyrosinase inhibitory activity, and antifungal activity of the methanol extracts. The results indicated that the extracts from 13 species exhibited high antioxidant potential, and their inhibitory concentrations that caused 50% scavenging of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (IC₅₀) were less than 10 μg/ml. The crude extract from Cylicodiscus gabunensis showed the highest antioxidant activity, and was even higher than that of (+)-catechin, which is known as a potent antioxidant. There was a good correlation between the antioxidant activity and the content of total phenolic compounds, indicating that phenolic compounds played a predominant role in the antioxidant property of the wood extracts. Among all 22 species, only 1 species, Milicia excelsa, contained extractives that showed very high tyrosinase inhibitory activity. The extracts from 9 species showed high antifungal activity. No consistent relationship was observed between the tyrosinase inhibitory activity or antifungal activity and the content of total phenolics in the extracts. Part of this article was presented at the 56th Annual Meeting of the Japan Wood Research Society, Akita, August 2006     

Isoprenoid-substituted flavonoids from wood of Artocarpus heterophyllus on B16 melanoma cells: Cytotoxicity and structural criteria

As a result of cytotoxicity-guided fractionation, nine flavonoids, artocarpin (1), cudraflavone C (2), 6-prenylapigenin (3), kuwanon C (4), norartocarpin (5), albanin A (6), cudraflavone B (7), brosimone I (8) and artocarpanone (9) were identified from the methanol extract of the wood of Artocarpus heterophyllus, known commonly as Nangka in Indonesia. A structure–activity investigation of the effect of these isolated compounds (1–9) and structurally related compounds on B16 melanoma cells indicated that isoprenoid moiety substitutions in flavonoids enhance their cytotoxicity, and that the position of attachment and the number of isoprenoid-substituent moieties per molecule influence flavonoid cytotoxicity.     

Antioxidant activity of heartwood extracts of Papua New Guinean woods

Antioxidant effects of methanol extracts from the heartwood of 23 Papua New Guinea (PNG) wood species were examined. The extract ofAmoora sp. (Meliaceae) showed the strongest antioxidant activity against lipid peroxidation in rabbit erythrocyte membrane and linoleic acid autoxidation. Also, the extract ofAmoora sp. showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicalscavenging activity. These results showed that the heartwood ofAmoora sp. is a possible source of antioxidative agents. The result of antioxidant activity-guided fractionation suggested that gallic acid, protocatechuic acid, and hydrolyzable tannins in the extract ofAmoora sp. caused the potent antioxidant activity.Part of this report was presented at the 51st Annual Meeting of the Japan Wood Research Society, Tokyo, 2001     

Novel stilbenoids isolated from the heartwood of <Emphasis Type="Italic">Shorea laeviforia</Emphasis>

 Two novel stilbenoids, laevifonol (an ε-viniferin-ascorbic acid hybrid compound) and laevifoside (an O-glucoside of ampelopsin A) were isolated from the heartwood of Shorea laeviforia. Their structures were elucidated by nuclear magnetic resonance spectroscopic evidence including HMQC, HMBC, and NOESY. The novel compounds and other known stilbenoids from S. laeviforia were evaluated for inhibitory activity against rat liver 5α-reductase. Positive inhibitory activities were observed in resveratrol dimers and tetramers. No inhibitory activity was detected in laevifonol and ampelopsin A glucosides, laevifoside, or hemsleyanoside, whereas inhibitory activity was seen in their aglycon. These results suggest that the hydrophilic moiety in these compounds may inhibit action with the hydrophobic active site of the enzyme. Received: November 21, 2001 / Accepted: February 8, 2002 Acknowledgment We are grateful to Dr. Wasrin Syafii (Bogor Agricultural University, Indonesia) for the collection of plant material. Correspondence to:Y. Hiramo