germanium and Chemical-and-Drug-Induced-Liver-Injury

In the present study, the protective effects of dietary Spirulina (SP) and germanium-containing Spirulina (GeSP) were compared in rats with liver injury induced by an intraperitoneal injection of d-galactosamine and lipopolysaccharide (GalN/LPS). Wistar rats were fed one of the following diets: the basal diet (GalN/LPS-CON group; n 6), the basal diet supplemented with 5 % SP or GeSP (GalN/LPS-SP and GalN/LPS-GeSP group, respectively; n 7 each). After administering these diets for 7 d, each rat was intraperitoneally injected with GalN/LPS. Increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were suppressed in the GalN/LPS-GeSP group (GalN/LPS-CON v. GalN/LPS-GeSP: ALT 1052 (sem 187) v. 509 (sem 88) IU/l and AST 2183 (sem 368) v. 1170 (sem 196) IU/l) following the injection of GalN/LPS. Plasma levels of interferon-γ (IFN-γ) and TNF-α in GeSP-fed rats were significantly lower when compared with those in the GalN/LPS-CON group (GalN/LPS-CON v. GalN/LPS-GeSP: IFN-γ 142·8 (sem 17·5) v. 66·8 (sem 9·7) pg/ml and TNF-α 72·3 (sem 15·4) v. 31·2 (sem 6·8) pg/ml). However, the decrease in these levels observed in the GalN/LPS-SP group was not as prominent as those observed in the GalN/LPS-GeSP group. Furthermore, the increase in liver catalase (CAT) and glutathione peroxidase (GPx) activities, as well as the level of oxidised glutathione (GSSG), was more suppressed in GeSP-fed rats (GalN/LPS-CON v. GalN/LPS-GeSP: CAT 457 (sem 47) v. 262 (sem 54) U/mg liver protein; GPx 1·30 (sem 0·11) v. 0·53 (sem 0·09) U/mg liver protein; GSSG 2·18 (sem 0·33) v. 1·31 (sem 0·24) mmol/kg liver) after the injection of GalN/LPS. These changes were more pronounced in the GalN/LPS-GeSP group than in the GalN/LPS-SP group. These results suggest that GeSP could afford a significant protective effect in the alleviation of GalN/LPS-induced hepatic damage. In addition, the results indicate that GeSP is more effective than SP.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Catalase; Chemical and Drug Induced Liver Injury; Dietary Supplements; Galactosamine; Germanium; Glutathione; Glutathione Peroxidase; Hepatitis; Interferon-gamma; Lipopolysaccharides; Liver; Male; Rats; Rats, Wistar; Spirulina; Tumor Necrosis Factor-alpha

Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.

Topics: Animals; Antibodies; Cells, Cultured; Chemical and Drug Induced Liver Injury; Coculture Techniques; Concanavalin A; Endothelium, Vascular; Female; Germanium; Interferon Inducers; Interferon-gamma; Liver; Macrophages; Mice; Mice, Inbred BALB C; Organometallic Compounds; Propionates; Rats; Rats, Inbred F344; Tumor Necrosis Factor-alpha

Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly.

Topics: Acidosis; Acute Kidney Injury; Adult; Chemical and Drug Induced Liver Injury; Female; Germanium; Humans; Lactates; Lactic Acid; Pancreatitis

The case history is described of a woman aged 57 years with renal, hepatic and muscular damage attributed to intake of germanium lactate-citrate (a cumulative dose of 32.1 g germanium) over at least one year, as alternative treatment of metastatic breast cancer. Histological examination of biopsies showed highly vacuolated cytoplasm of the epithelial cells of the distal renal tubules and micro- and macrovesicular steatosis of centrilobular hepatocytes. After discontinuation of the germanium, serum aminotransferases and creatine kinase values returned to normal, but moderately severe renal impairment persisted.

Topics: Breast Neoplasms; Chemical and Drug Induced Liver Injury; Citrates; Complementary Therapies; Female; Germanium; Humans; Kidney; Lactates; Liver; Middle Aged; Muscles

Topics: Adult; Aged; Cerebral Hemorrhage; Chemical and Drug Induced Liver Injury; Drug Evaluation; Female; Germanium; Glioma; Humans; Male; Middle Aged; Nervous System Neoplasms; Organometallic Compounds; Spiro Compounds

Topics: Adipose Tissue; Animals; Blood Chemical Analysis; Bone and Bones; Brain; Chemical and Drug Induced Liver Injury; Germanium; Hepatitis; Kidney; Lung; Metabolism; Mice; Pancreas; Research; Spectrophotometry; Spleen; Toxicology