In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg-1 day-1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3% for piplartine and 55.1 and 56.8% for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

De Roma aeterna 2

Arkit: 1 arkintunnukseton lehti, B4. - S. [2] tyhjä.

De Roma aeterna 1

Painovuosi nimekkeestä.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg,ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

De Marco Attilio Regulo

Invokaatio: I.N.J.

Desenvolvimento vegetativo de plantas e qualidade fisiológica de sementes de arroz produzidas em áreas de recuperação de pastagem

O presente trabalho teve como objetivo avaliar o desenvolvimento vegetativo e a qualidade fisiológica de sementes de cultivares de arroz produzidas em sistemas alternativos para a renovação de pastagem. O trabalho foi conduzido no município de Alta Floresta-MT, na safra 2006/07. O delineamento experimental utilizado foi o de blocos casualizados em esquema fatorial 2x8, perfazendo 16 tratamentos, constituídos pela combinação 2 cultivares de arroz (Oryza sativa L.) (BRS Primavera e BEST 2000) e 8 modos de redução no desenvolvimento da braquiária (Brachiaria brizantha cv. Marandu), sendo 4 doses reduzidas do herbicida cyhalofop butil (180 g L-1) (0; 0,40; 0,80 e 1,2 L ha-1) e a semeadura da braquiária a lanço e com incorporação aos 10 e 20 dias após a emergência do arroz. Todos os tratamentos tiveram 4 repetições. Nos tratamentos em que a braquiária recebeu doses reduzidas de herbicida, a forrageira foi semeada juntamente com o arroz. Foram avaliadas as seguintes características vegetativas: altura de planta, comprimento e diâmetro de entre nó e índice de área foliar e os seguintes testes de qualidade fisiológica de sementes: germinação, primeira contagem, índice de velocidade de germinação, condutividade elétrica e envelhecimento acelerado. O cultivar BRS Primavera produziu sementes de melhor qualidade; todas as alternativas estudadas mostram-se viáveis para a produção de sementes e a região de Alta Floresta mostra-se apta para a produção de sementes de arroz.