Biological Activities and Medical Research of Aminoguanidine Bicarbonate

Biological Activity

 

1. Antioxidant Effect

 

In vivo, oxidative stress is a key factor in the development and progression of many diseases. Aminoguanidine bicarbonate can exert antioxidant effects by regulating the activity of related enzymes, reducing the production of reactive oxygen species (ROS), and enhancing the function of intracellular antioxidant enzyme systems, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), thereby helping cells resist oxidative damage. For example, in some cell experiments, treatment with aminoguanidine bicarbonate in cells exposed to oxidative stress significantly reduced intracellular ROS levels, increased antioxidant enzyme activity, and improved cell survival.

 

2. Anti-inflammatory Activity

 

Inflammation plays a key role in the progression of many diseases. Aminoguanidine bicarbonate can inhibit the release of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). It acts on inflammatory signaling pathways, blocking the activation of related proteins and thereby alleviating inflammatory responses. In animal models of induced inflammation, administration of aminoguanidine bicarbonate alleviated symptoms such as redness, swelling, and pain at the site of inflammation. Histopathological examination also revealed a decrease in inflammatory cell infiltration and expression of inflammatory factors.

 

3. Inhibition of Nitric Oxide Synthase (NOS)

 

Nitric oxide (NO) plays a complex role in physiological and pathological processes. Aminoguanidine bicarbonate is a NOS inhibitor that inhibits both constitutive and inducible NOS activity. In the intestinal microvasculature, by inhibiting NOS activity, it reduces excessive NO production, thereby regulating vascular tone and improving microcirculation. This NOS inhibitory effect is of great significance in the study of diseases such as cardiovascular and neurological disorders.

 

Applications in Medical Research

 

1. Chronic Renal Failure Treatment Research

 

Patients with chronic renal failure often face elevated creatinine levels. Creatinine, a byproduct of muscle metabolism, is normally excreted through the kidneys, but excretion is impaired when renal function is impaired. Aminoguanidine bicarbonate has shown positive effects in the treatment of chronic renal failure. It binds to creatinine, forming a more readily excretable substance, thereby lowering blood creatinine levels, reducing the burden on the kidneys, and slowing the progression of renal failure. In a double-blind randomized controlled trial (RCT) of 690 patients with diabetic nephropathy, patients were divided into three groups: 150mg (n = 229) and 300mg (n = 225) of aminoguanidine for 2 to 4 years. The results showed that while there was no significant difference in the progression of serum creatinine doubling in the aminoguanidine group compared with the placebo group, aminoguanidine slowed the decline in estimated glomerular filtration rate and reduced total urinary protein. However, clinical use has also revealed that aminoguanidine bicarbonate may cause side effects such as nausea, vomiting, and diarrhea, necessitating close monitoring of patient responses.

 

2. Cancer Therapy Research

 

Aminoguanidine bicarbonate has also demonstrated potential value in cancer therapy research. It participates in the synthesis of several anti-tumor drugs, including compounds with anti-tumor and anti-leukemia activity. Furthermore, its antioxidant and anti-inflammatory properties can help improve the tumor microenvironment and inhibit tumor cell growth and metastasis. For example, in some in vitro tumor cell culture experiments, aminoguanidine bicarbonate has been shown to inhibit tumor cell proliferation and induce apoptosis. Furthermore, in animal tumor models, it has been shown to slow tumor growth to a certain extent.

 

3. Neurological Disease Research

 

Aminoguanidine bicarbonate has also garnered attention in the study of neurological diseases such as Alzheimer's disease and multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) models. Abnormal oxidative stress and inflammation are present in the brains of patients with Alzheimer's disease. The antioxidant and anti-inflammatory effects of aminoguanidine bicarbonate can mitigate neuronal damage and improve neurological function. In the EAE model, it modulates the immune system and inhibits inflammatory damage to neural tissue, providing a new research direction for the treatment of multiple sclerosis.

 

Other Clinical Applications

 

In a peritoneal dialysis (PD) rat model, aminoguanidine bicarbonate was evaluated by adding it to peritoneal dialysis fluid (PDF). The study found that aminoguanidine bicarbonate effectively cleared various glucose degradation products (GDPs) from PDF. Daily exposure to PDF for 5 weeks significantly increased leukocyte rolling in mesenteric venules, while addition of aminoguanidine bicarbonate reduced this by approximately 50% (P < 0.02). Furthermore, PDF-induced vascular leakage was observed in rats treated with aminoguanidine bicarbonate, but not with PDF alone. Evaluation of the viscera and parietal peritoneum revealed that PDF instillation induced angiogenesis and fibrosis. Addition of aminoguanidine bicarbonate significantly reduced vascular density in the greater omentum and parietal peritoneum (P < 0.04), but had no effect on the mesentery. It also significantly attenuated PDF-induced fibrosis (P < 0.02) and inhibited the accumulation of advanced glycation end products (AGEs) in the mesentery induced by PDF instillation.

 

In a diabetic rat model, female Wistar rats were divided into two groups after induction of diabetes: the AGDM group (n = 11) received 1 g/L aminoguanidine bicarbonate in drinking water, the DC group (n = 12) received tap water alone, and there were also control groups: AGH (n = 8) receiving aminoguanidine and HC (n = 8) receiving tap water. At the end of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was lower in the AGDM group than in the diabetic control group. The glomerular basement membrane (GBM) thickness of diabetic rats was increased compared with that of the AGDM and HC groups. However, the distribution and number of Alcian blue-stained particles in the GBM of the AGDM group were similar to those of healthy controls. This suggests that aminoguanidine prevents the reduction of anionic charged molecules in the GBM and GBM thickening, which may be one of its mechanisms for reducing proteinuria in diabetic rats.

 

In a study of type 2 diabetic mice, the leptin receptor-deficient db/db (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model were used. Starting at 8 weeks of age, mice were treated with metformin (MET), aminoguanidine (AG), or a control group (receiving an equal volume of saline). The study found that guanidine compounds (such as AG and MET) inhibited AGE formation, significantly improved the microstructure and biomechanical strength of diabetic bones, and promoted fracture healing.