RESUMEN
Lycopene, the main fat-soluble pigment responsible for the red color of ripe tomatoes, is a symmetrical tetraterpene comprising eight isoprene units. In vitro and in vivo studies have shown that lycopene acts as a potent antioxidant; it is 100 times more effective than vitamin E and 125 times more effective than glutathione as an antioxidant. Here, we divided BALB/c male mice into three equal groups: control, Concanavalin A (Con A), and Con A and lycopene. The control group mice received only vehicle by intraperitoneal injection, the Con A group mice were given Con A, and the Con A and lycopene group mice received Con A and lycopene. The results showed that Con A administration increased histopathological damage, and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were increased in serum samples whereas the levels of these compounds were significantly decreased in the Con A and lycopene group compared to the Con A group. Furthermore, we observed that lycopene led to an increase in cell viability and cell growth. The results of this study revealed that lycopene might be a useful hepatoprotective agent for reducing increased proinflammatory cytokine levels, and for increasing cell viability and cell growth.
Asunto(s)
Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Hepatopatías/prevención & control , Licopeno/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Concanavalina A/toxicidad , Modelos Animales de Enfermedad , Interferón gamma/sangre , Interleucina-6/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury. Here, we determined if NPP50 modified with the amino group (NPP50-NH2), carboxyl group (NPP50-COOH), or palladium (Pd-NPP50) caused liver or kidney injury when co-administered with PQ or CDDP. The results showed that when NPP50-NH2, NPP50-COOH, or Pd-NPP50 was administered alone via the mouse tail vein, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) did not increase or cause injury. When NPP50, NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with PQ, serum levels of ALT and AST increased in the NPP50 group but did not increase in the NPP50-NH2, NPP50-COOH, or Pd-NPP50 groups. When NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with CDDP, ALT, AST, and BUN values did not increase. These data suggest that injury due to the interaction of polystyrene nanoparticles with CDDP or PQ can be suppressed by changes in the surface charge of nanoparticles or by Pd modification.
Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cisplatino/química , Cisplatino/uso terapéutico , Herbicidas/química , Herbicidas/toxicidad , Enfermedades Renales/inducido químicamente , Nanopartículas/química , Paladio/química , Paladio/farmacología , Paraquat/química , Paraquat/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Nitrógeno de la Urea Sanguínea , Enfermedades Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , PoliestirenosRESUMEN
Nanomaterials are frequently used in microelectronics, cosmetics, and sunscreens. Platinum reagents are commonly used in disease diagnosis, cosmetics, and the food industry. Although research into the development of nanomaterialbased drug delivery systems has yielded promising results, the toxicity of these materials is not fully understood. We investigated the toxicity and drug interactions of 1- and 8-nm diameter platinum nanoparticles (nPt1 and nPt8, respectively) in mice. Acute hepato-renal toxicity of intravenously administered platinum nanoparticles was evaluated biochemically and histologically. Dose-dependent increases in serum markers of hepato-renal function (serum aminotransferases and blood urea nitrogen) were observed following administration of nPt1, whereas nPt8 had no effect, even at 20 mg/kg. Moreover, nPt1 induced interleukin (IL)-6 and IL-1ß production 3 and 6 hours after administration. The effect of nPts on drug-induced toxicity was evaluated in mice injected intraperitoneally with carbon tetrachloride or cisplatin, with or without intravenous administration of platinum nanoparticles. All treatments in the absence of nanoparticles were non-lethal and resulted in moderate toxicity. However, exacerbated toxicity was observed in mice injected with carbon tetrachloride or cisplatin together with nPt1, but not in mice co-injected with nPt8. We found that nPt1 cause hepato-renal damage, and the effect is enhanced by chemical inducers of hepatotoxicity and nephrotoxicity. This is the first report demonstrating that nPt1 not only are hepatotoxic and nephrotoxic but also exacerbate drug toxicity. These findings will be useful for future nanotechnology and nanoscience research.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Nanopartículas del Metal/toxicidad , Platino (Metal)/toxicidad , Alanina Transaminasa/sangre , Animales , Antineoplásicos/toxicidad , Aspartato Aminotransferasas/sangre , Nitrógeno de la Urea Sanguínea , Tetracloruro de Carbono/toxicidad , Cisplatino/toxicidad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Interleucina-1beta/biosíntesis , Interleucina-1beta/genética , Interleucina-6/biosíntesis , Interleucina-6/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de la PartículaRESUMEN
We identified a novel gene of Drosophila melanogaster, Male-specific IDGF (MSI), encoding a transmembrane signaling molecule with exclusive expression in the testis. This molecule (MSI) contains a single transmembrane domain and has 35% amino acid identity with insect-derived growth factor (IDGF), a soluble growth factor for embryonic cells of the flesh fly, Sarcophaga peregrina. When MSI was exogenously expressed in Schneiders's line 2 cells, it was shown to be localized on the cell surface and exhibits growth factor activity, suggesting that MSI is a membrane-bound extracellular signaling molecule. Gene expression studies revealed that MSI mRNA was restricted to mature primary spermatocytes, whereas MSI was detected in the cells at the later developmental stages. Analysis using four meiotic arrest mutants, aly, can, mia, and sa suggested that MSI is involved in spermiogenesis, the final differentiation step of spermatogenesis. These results suggest that MSI is an extracellular signaling molecule participating in spermatogenesis and is a new member of the IDGF family.
Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster/genética , Proteínas de la Membrana/genética , Testículo/química , Secuencia de Aminoácidos , Animales , Aplysia , Secuencia de Bases , Células Cultivadas , Expresión Génica , Masculino , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Espermatocitos/metabolismo , Testículo/metabolismoRESUMEN
Previously, we identified two proteins with molecular masses of 200 and 210 kDa in basement membranes of Sarcophaga imaginal discs as substrates for cathepsin L [Homma, K. and Natori, S. (1996) Eur. J. Biochem. 240, 443-447]. Here we demonstrated that the same proteins were also present in the basement membranes of larval brains. These proteins were suggested to be digested by cathepsin L secreted from the larval brains in response to 20-HE. From the behavior of these proteins during metamorphosis, we concluded that the basement membranes of larval brains are degraded at the early pupal stage and synthesized again at the late pupal stage, coinciding with the timing of brain remodeling that takes place during metamorphosis. Possibly, the transient disappearance of the basement membranes makes brain remodeling easier, and cathepsin L is suggested to play a crucial role in the degradation of the basement membranes.