The Authoritative Germanium Sesquioxide Resource

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Analytical •AntimutagenicAntioxidant •Antiviral •Arthritis •Atherosclerosis •Bioavailability •CancerCataracts  •Cervix •DNA Repair •Fibrosis •Free Radical ScavengingHazards •Heart •History •Immune SystemKidneysInflammation •Liver •Osteoporosis •Pain Management Pharmacology •Reviews •Safety •Uterus

Antioxidant, Liver
Protective role of germanium-132 against paraquat-induced oxidative stress in the livers of senescence-accelerated mice.
J Toxicol Environ Health A. 1999 Nov 12;58(5):289-97.

Yang MK, Kim YG.

Department of Biological Science, College of Natural Sciences, Chosun University, Dong-ku, Kwangju, Korea.

The effects of the synthetic antioxidant germanium (Ge-132) were studied on liver oxidant damage induced by paraquat (PQ) in senescence-accelerated mice (SAM). PQ administered intravenously to SAM-P/8 (susceptible) or SAM-R/1 (resistant) mice increased liver DNA strand breakage and malondialdehyde (MDA) levels, indicators of oxidant damage. Ge-132 effectively blocked the PQ-induced effects on liver DNA strand breaks and MDA levels. In addition, Ge-132 significantly elevated the activities of hepatic superoxide dismutase (SOD) and catalase following PQ pretreatment. Histopathologically, Ge-132 inhibited PQ-induced hepatic mitochondrial injury in both strains, but more effectively in the susceptible strain. Data suggest that Ge-132 may be useful as an antioxidant in view of its ability to prevent PQ-induced hepatic oxidant injury.

Immune System, Liver
Propagermanium: a nonspecific immune modulator for chronic hepatitis B. J Gastroenterol. 2003;38(6):525-32.

Hirayama C, Suzuki H, Ito M, Okumura M, Oda T.

Second Department of Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.

Although antiviral agents have been adopted for the management of chronic hepatitis B, they have only limited efficacy because of the underlying impaired immune status. Propagermanium, a hydrophilic polymer of 3-oxygermyl propionate, has been reported to have potent immune modulatory activity associated with antiinflammatory and antineoplastic properties. For example, propagermanium augments lymphocyte functions in CD4 and CD8 cells, and in natural killer (NK) cells, and induces the production of several cytokines. A controlled pilot study of 16-week treatment with propagermanium for chronic hepatitis B (of moderate and mild grades on hepatic histology) revealed a sustained clearance of hepatitis B e (HBe) antigen and a favorable biochemical response at week 16 of treatment and at week 48 post-treatment. An open study also supported the clearance of hepatitis B virus from the blood and the possible improvement of histologic grading in the liver. There were few adverse events. A postmarketing survey, however, revealed the occurrence of moderate to severe liver damage after the treatment in about 4% of patients. Despite the exact nature of the liver damage being unclear, a putative cause is the swift removal of virus-infected hepatocytes by an immune reaction through the treatment. A subtle balance between host and viral conditions is the factor which most determines hepatitis B virus persistence. The rationale for a nonspecific immune modulator for the treatment of chronic hepatitis B will be the restoration of cellular immune responsiveness to viral infection. Although the cellular immunity for hepatitis B virus prior to the treatment should be studied, adequate observation of hepatic functions and viral markers in the recipients is clinically useful to predict liver failure during the treatment. In summary, the propagermanium regimen offers a potent and safe approach that is cost-effective for appropriate chronic hepatitis B patients with reserve hepatic capacity, and will provide new perspectives for immune therapy in chronic hepatitis B.

Protection against concanavalin A-induced murine liver injury by the organic germanium compound, propagermanium. Scand J Immunol. 1998 Dec;48(6):605-14.

Ishiwata Y, Yokochi S, Hashimoto H, Ninomiya F, Suzuki T.

Developmental Research Department, Sanwa Kagaku Kenkyusho Co. Ltd, Mie, Japan.

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.

Liver, Antiviral
New management of hepatitis B virus.  Nippon Naika Gakkai Zasshi. 1999 Apr 10;88(4):713-7.

Sata M, Kumashiro R.

PMID: 10341661 [PubMed - indexed for MEDLINE


Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice.  Scand J Immunol. 1998 Aug;48(2):183-91.

Yokochi S, Ishiwata Y, Hashimoto H, Ninomiya F, Suzuki T.

Developmental Research Department, Sanwa Kagaku Kenkyusho Co., Ltd, Mie, Japan.

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice. PMID: 9716110 [PubMed - indexed for MEDLINE

Liver, Immune System
Endogenous gamma interferon production may protect against hepatic cirrhosis and administration of exogenous gamma interferon may protect individuals prone to cirrhosis.  Med Hypotheses. 1987 Apr;22(4):415-9.

Sharpe RJ.

Hepatic cirrhosis is characterized by the replacement of normal liver parenchyma by collagenous fibrous tissue. Although hepatocytes in the adult retain the ability to divide, under certain circumstances hepatocyte death leads to replacement with fibroblasts and collagen. Whether a particular form of hepatocyte injury leads to cirrhosis is dependent upon the stimulus for the injury and is also highly variable between individuals. It has recently been shown that gamma interferon inhibits collagen synthesis in vitro and fibrosis in vivo. I suggest that individuals who are prone to hepatic cirrhosis from a given stimulus are low producers of gamma interferon while high gamma interferon producers are relatively protected from cirrhosis. I also hypothesize that exogenous gamma interferon administration may halt or slow the progression of cirrhosis in patients with early progressive cirrhosis. Alternatively, endogenous gamma interferon production could be stimulated in these patients with progressive cirrhosis. One agent which may be useful for inducing endogenous gamma interferon is GE-132, an organogermanium. PMID: 3108636 [PubMed - indexed for MEDLINE]

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