Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats.

OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFkappaB and TNF-alpha in liver cancer-induced rats. METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1% ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFkappaB and TNF-alpha. RESULTS: The expression of NFkappaB was detected in the choline-deficient diet group, with 88.3 +/- 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFkappaB was significantly reduced, to 32.35 +/- 1.34% (p<0.05). In the choline-deficient diet group, 83.3 +/- 4.52% of samples showed positive staining of TNF-alpha, which was significantly reduced to 7.94 +/- 1.32% (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFkappaB and TNF-alpha in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group. CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFkappaB and TNF-alpha in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFkappaB through the suppression of the pro-inflammatory TNF-alpha.

Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats

OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFêB and TNF-á in liver cancer-induced rats. METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1 percent ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFêB and TNF-á. RESULTS: The expression of NFêB was detected in the choline-deficient diet group, with 88.3 ± 1.83 percent of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFêB was significantly reduced, to 32.35 ± 1.34 percent (p<0.05). In the choline-deficient diet group, 83.3 ± 4.52 percent of samples showed positive staining of TNF-á, which was significantly reduced to 7.94 ± 1.32 percent (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFêB and TNF-á in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group. CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFêB and TNF-á in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFêB through the suppression of the pro-inflammatory TNF-á.

A dominant negative effect of eth-1r, a mutant allele of the Neurospora crassa S-adenosylmethionine synthetase-encoding gene conferring resistance to the methionine toxic analogue ethionine.

eth-1r, a thermosensitive allele of the Neurospora crassa S-adenosylmethionine (AdoMet) synthetase gene that confers ethionine resistance, has been cloned and sequenced. Replacement of an aspartic amino acid residue (D48-->N48), perfectly conserved in prokaryotic, fungal and higher eukaryotic AdoMet synthetases, was found responsible for both thermosensitivity and ethionine resistance conferred by eth-1r. Gene fusion constructs, designed to overexpress eth-1r in vivo, render transformant cells resistant to ethionine. Dominance of ethionine resistance was further demonstrated in eth-1+/eth-1r partial diploids carrying identical gene doses of both alleles. Heterozygous eth-1+/eth-1r cells have, at the same time, both the thermotolerance conferred by eth-1+ and the ethionine-resistant phenotype conferred by eth-1r. AdoMet levels and AdoMet synthetase activities were dramatically decreased in heterozygous eth-1+/ eth-1r cells. We propose that this negative effect exerted by eth-1r results from the in vivo formation of heteromeric eth-1+/eth-1r AdoMet synthetase molecules.

On the mechanism of protective action of cold acclimatization against carbon tetrachloride- and ethionine-induced fatty liver.

In this study the hepatic lipoprotein lipase (LPL) activity was evaluated in adult female mice acclimatized at 5 degrees C and submitted to carbon tetrachloride (CCl4) or ethionine, in order to determine the possible role of this enzyme in the fatty liver. The results were compared with those obtained in mice kept at room temperature (27 degrees C) that received the same hepatoesteatosis inducing agent. In contrast to animals kept at room temperature, in cold acclimatized mice neither the enhancement of the LPL-liver activity by the action of CCl4 or ethionine occurred nor the development of fatty infiltration in the liver was observed. We conclude that the low temperature induced a protective effect against CCl4- or ethionine-induced fatty liver that was correlated with the no-increase of the hepatic LPL activity.

Structural and cytochemical study of the rat exocrine pancreas treated with dl-ethionine. I. Multilayered bodies and lesioned areas.

The fine structural changes and the reactivity for acid phosphatase (AcPase) and thiamine pyrophosphatase (TPPase) were studied in thin sections from rat pancreatic acinar cells exposed to dl-ethionine for 2-10 days. The cells from ad libitum and pair-fed controls exhibit occasionally 0.2-0.6 microns circular profiles showing reaction for AcPase and considered as presumptive lysosomes. At days 2 and 4 of dl-ethionine treatment the acinar cells exhibit presumptive lysosomes, autophagosomes and membrane-bounded cytoplasmic areas devoid of electron density and AcPase activity, containing scattered membranous elements. These regions were named lesioned areas. On 6th, 8th and 10th days a membrane bound anomalous cytoplasmic structure that represents a dense pile of layered membrane-like material (multilayered bodies, MB) was seen. The MBs consistently show AcPase activity and in rare instances TPPase activity. Freeze fracture studies reveal that the limiting membrane of the MBs has intramembranous particles whereas the multilayered membranous contents are devoid of such particles. The structure and disposition of the lamellae of the MBs seen in the replicas are similar to those of artificially prepared phospholipidic membranes.

Morphometric evaluation of acinar cell number and volume in rat pancreas treated with dl-ethionine

1. The morphological changes of the pancreas induced by administration of dl-eyhionine were determined for treated rats and for a group of pair-fed untreated controls in order to separate the direct effect of dl-ethionine from the effect of accompanying reduction of food intake. 2. Adult male Wistar rats were studied in 3 groups of 10 animals each: 1) fed ad libitum and treated daily with dl-ethionine (35 mg/100 g body weight, ip) for 10 days; 2) treated daily with vehicle (saline) as group 1 and pair-fed to group 1; 3) treated daily with vehicle (saline) and fed ad libitum. Two rats from each group were killed on days 2, 4, 6, 8 and 10 to characterize the ancreas in terms of morphological properties using morphometric analysis. 3. Exposure to del-ethionine induced a progressive and significant decrease in both pancreas weight and acinar cell number and volume. Pair feeding induced less pronounced decreases in pancreas weight and acinar cell volume. Pancreas weight was 125 mg/100g body weight for dl-ethionine-treated vs 205mg/100g body weight for pair-fed controls and 320 mg/100 g body weight for ad libitum-fed controls after 10 days. Acinar cell number (x ñ o-/Vn): 175 x 10**6 ñ 28.4 per µm3 for dl-ethionine-treated vs 221 x 10**6 ñ 17.3 per µm3 for pair-fed controls and 271 x 10**6 ñ 23.9 per µm3 for ad libitum-fed controls. Acinar cell volume (x ñ o-/Vn) was 1292 ñ 65.4 µm3 for dl-ethionine-treated vs 1436 ñ 74.9 µm3 for pair-fed controls and 1758 ñ 117.1 µm3 for ad libitum-fed controls. 4. Continuous treatment with dl-ethionine for 10 days induced pancreatic weight loss for two main reasons: 1) reduction of the number of acinar cells, an effect apparently induced by dl-ethionine administration, and 2) acinar cell atrophy consequent to food restriction

Morphometric evaluation of acinar cell number and volume in rat pancreas treated with dl-ethionine.

1. The morphological changes of the pancreas induced by administration of dl-ethionine were determined for treated rats and for a group of pair-fed untreated controls in order to separate the direct effect of dl-ethionine from the effect of accompanying reduction of food intake. 2. Adult male Wistar rats were studied in 3 groups of 10 animals each: 1) fed ad libitum and treated daily with dl-ethionine (35 mg/100 g body weight, ip) for 10 days; 2) treated daily with vehicle (saline) as group 1 and pair-fed to group 1; 3) treated daily with vehicle (saline) and fed ad libitum. Two rats from each group were killed on days 2, 4, 6, 8 and 10 to characterize the pancreas in terms of morphological properties using morphometric analysis. 3. Exposure to dl-ethionine induced a progressive and significant decrease in both pancreas weight and acinar cell number and volume. Pair feeding induced less pronounced decreases in pancreas weight and acinar cell volume. Pancreas weight was 125 mg/100 g body weight for dl-ethionine-treated vs 205 mg/100 g body weight for pair-fed controls and 320 mg/100 g body weight for ad libitum-fed controls after 10 days. Acinar cell number (x +/- sigma/square root of n): 175 x 10(6) +/- 28.4 per micron3 for dl-ethionine-treated vs 221 x 10(6) +/- 17.3 per micron3 for pair-fed controls and 271 x 10(6) +/- 23.9 per micron3 for ad libitum-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Mecanismo teórico de la hepatocarcinogénesis / Theoretical mechanism of ethionine hepatocarcinogenesis

En resumen, parece ser que el proceso necesario, al menos conceptualmente que le permita a uno construir una noción adecuada del mecanismo involucrado durante la carcinogénesis inducida por etionina, puede ser relevante a un proceso más general y fundamental aplicable a todos los carcinógenos. Se ha descrito un intento que trata de aportar un mecanismo considerado en este artículo, también enfatiza la importancia de la activación de proteínas embriónicas como un ejemplo de un proceso más general que se requiere para la carcinogénesis

Efecto de la etionina sobre el hígado de rata en condiciones de diferente aporte de proteina en la dieta / Ethionine effects on rat liver under different protein dietary contents

Durante el desarrollo de la vida de un ser vivo reviste sinbgular importancia la capacidad de adaptación de su organismo a los cambios cambientales. Esta adaptabilidad parece depender en grado sumo del aporte de proteínas en la alimentación. Por ejemplo, la deficiencia proteínica en la dieta provoca un marcado descenso de las defensas del organismo, elevando a la vez su susceptibilidad a los agentes tóxicos ambientales cuyo número y variedad actualmente cada vez es mayor. En estas condiciones es clara la necesidad de la fórmula óptima alimentaria como media de protección fisiológico frente a un agresivo entorno. Este trabajo es un grano de arenas, camino de esta búsqueda, el cual se realizó en animales de experimentación (ratas) a nivel subcelular (lisosoma), abarcando dos aspectos: morfológico y enzimático (enzimas marcadoras-fosfatasa ácida, ribonucleasa ácida y catepsina). Se encontró: la etionina en condiciones de alimentación con aporte normal proteínico (18.5%) provoca alteraciones leves en los hepatocitos (infiltración grasa periportal, mínimas alteraciones del patrón enzimático y de la permeabilidad celular). En condiciones de alimentación deficiente en proteínas la manifestación histológica es más severas (disminución de ARN celular, infiltración grasa difusa), siendo mínimo el cambio en el patrón enzimático y en la permeabilidad celular. En condiciones de alimentación con exceso de proteína (44.5%) los cambios histológicos y de permeabilidad son discretos y se registró una tendencia a la transformación favorable anabólica patrón enzimático. Se concluye: el aporte elevado de proteína en la dieta surte en ratas el efecto de antídoto de la acción hepatotóxica de la etionina

Açäo de sais de cobre sobre a xantina desidrogenase na carcinogênese hepática de ratas / Action of copper salts on xanthine dehydrogenase in hepatic carcinogenesis of rats

Estudou-se a inibiçäo da atividade de xantina desidrogenase (XD) do soro de ratas pelo acetado de cobre (AcCu). Verificou-se também a relaçäo entre a atividade XD e a degeneraçäo hepática e carcinogênese pela D-L-etionina. Experiências mostraram que a AcCu é um potente inibidor da XD e que esta inibiçäo é näo-competitiva quando se mantém constante a concentraçäo do receptor de eletrons, e do tipo competitivo quando esta concentraçäo varia permanecendo constante a concentraçäo de substrato. Comparando-se estes estudos com os resultados da dosagem da atividade de xantina oxidase (oxigênio como receptor de eletrons) sugere-se que radicais estariam, envolvidos na açäo citotóxica do complexo AcCu-etionina com provável necessidade de ocorrência de uma reaçäo de reduçäo

Phosphoenolpyruvate carboxykinase of kidney

A method for the assay of phosphoenolpyruvate carboxykinase is presented, based on the enzymic determination of the phosphoenolpyruvate produced by the enzyme reaction. The subcellular distribution of phosphoenolpyruvate carboxykinase in the kidney of several animal species resembled the distribution in the liver. The rise in enzyme activity in the kidney cortex of rats made acidotic by feeding with ammonium chloride was not prevented by the administration of ethionine or actinomycin. The possibility is suggested that in the kidney acidosis causes activation of an inactive form of the enzyme already present. (AU)