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CN-121971425-A - Use of glutamine for the prevention and/or treatment of lead poisoning

CN121971425ACN 121971425 ACN121971425 ACN 121971425ACN-121971425-A

Abstract

The invention relates to application of glutamine in preventing or treating lead neurotoxicity. The research of the invention shows that the glutamine has obvious improvement effect on the neurobehavioral injury and neuroinflammatory reaction caused by lead poisoning. The new application of the glutamine of the invention provides a new medicine choice for the treatment of lead poisoning, especially for the treatment of lead neurotoxicity, and has great application potential and value.

Inventors

  • MENG XIAOJING
  • Tan Meitao
  • CHEN KAIJU
  • FAN HONGYING
  • ZENG WEISEN

Assignees

  • 南方医科大学

Dates

Publication Date
20260505
Application Date
20260402

Claims (8)

  1. 1. Use of glutamine in the manufacture of a product for the prevention and/or treatment of lead poisoning.
  2. 2. The use according to claim 1, characterized in that the use comprises the prevention and/or treatment of lead-induced neurotoxicity.
  3. 3. The use according to claim 2, wherein the use comprises the treatment of learning and memory impairment caused by lead poisoning.
  4. 4. The use according to any one of claims 1-3, wherein the use comprises at least one of a-d improving the pathological changes in the CA3 and DG regions caused by lead exposure; b. Improving the decrease of glutamine, glutamic acid and alpha KG content of the hippocampal tissue of the mice caused by lead exposure; c. reduces the expression level of inflammatory factors IL-6 and TNF-alpha. D. up-regulating the expression level of αkg.
  5. 5. Use according to claim 1, characterized in that the product is a medicament, the active ingredient of which is glutamine.
  6. 6. The use according to claim 5, wherein the pharmaceutical dosage form is a capsule, a soft capsule, a granule, a tablet, a dispersible tablet, a granule, or an oral liquid.
  7. 7. A use according to any one of claims 1-3, wherein the subject to which the use is applicable is a mammal.
  8. 8. The use according to claim 7, wherein the mammal is a human.

Description

Use of glutamine for the prevention and/or treatment of lead poisoning Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of glutamine in preventing and/or treating lead poisoning. Background Lead is a heavy metal poison widely existing in the environment, and the wide application of lead causes the lead to enter the environment in the form of different compounds along with industrial waste, sewage tail gas and the like, and finally accumulate in the human body to cause damage to the human body. The global disease burden dataset shows that the number of deaths caused by lead exposure has increased from 53 to 90 tens of thousands worldwide from 1990 to 2019, and the Disability Adjustment Life Years (DALY) has increased from about 1600 to 2100 tens of thousands, indicating that lead exposure has become a global serious public health problem. The toxic effects of lead on the central nervous system have been widely demonstrated, and the hippocampus is a critical brain area for learning and memory, and is particularly sensitive to lead exposure. Lead can cause damage to hippocampal function by direct injury to neurons of the hippocampus or by activation of microglial-induced neuroinflammation, ultimately leading to decline in learning and memory function. Lead exposure affects gene expression in the hippocampus of mice, with microglia being most susceptible to it. Microglia, which are resident macrophages of the central nervous system, are the first line of immune defense to maintain homeostasis of the central nervous system. When the body receives the inflammation signal, microglia in a 'resting' state can be converted into an activated state to maintain the health of the central nervous system. During lead poisoning, microglial energy metabolism is disturbed and may trigger inflammatory reactions mediated by the microglial cells. The main drugs currently used clinically for the treatment of lead poisoning are lead chelators such as disodium calcium edetate and sodium dimercaptosuccinate. However, these drugs have relatively remarkable side effects and have limited effects of improving neurotoxicity due to long-term lead exposure. Therefore, the development of an intervention means which has high safety and small side effect and can effectively relieve lead-induced neurotoxicity has important significance. Glutamine (Gln) is a five-carbon amino acid having a molecular weight of 146.15kDa and is classified into two forms, L-form (L-form) and DL-form (rac) according to a steric structure, wherein L-Gln is a naturally occurring form thereof, which is widely present in foods. Glutamine is the most abundant non-essential amino acid in the human body and is important for the growth, proliferation, immune function and the like of cells. The glutamine absorption and metabolism process in the organism is finely regulated by a series of enzymes. The glutamine transporter is responsible for transporting extracellular glutamine into the cell, and after intracellular glutamine enters mitochondria, glutaminase can break down intracellular glutamine into glutamate. Glutamate dehydrogenase can then further decompose glutamate into alpha-ketoglutarate (αkg). However, whether glutamine can be used to treat lead poisoning is not certain, and in particular the effect on lead neurotoxicity is not clear. Disclosure of Invention Based on this, it is an object of the present invention to provide a new use of glutamine in medicine, the use of glutamine in the prevention and/or treatment of lead poisoning, including in lead neurotoxicity. In a first aspect, the invention provides the use of glutamine in the manufacture of a product for the treatment of lead poisoning. In some embodiments, the use is the prevention and/or treatment of lead neurotoxicity. In some embodiments, the product is a medicament with an active ingredient comprising glutamine. In some embodiments, the pharmaceutical dosage form is a capsule, a soft capsule, a granule, a tablet, a dispersible tablet, a granule, an oral liquid, or the like. In some embodiments, the use comprises treating learning and memory impairment caused by lead exposure. In some embodiments, the use comprises ameliorating pathological changes in the CA3 and DG regions caused by lead exposure. In some embodiments, the use comprises ameliorating a decrease in glutamine, glutamate, and αkg content in hippocampal tissue of a mouse caused by lead exposure. In some embodiments, the use includes reducing the expression levels of inflammatory factors IL-6 and TNF- α. In some embodiments, the use comprises up-regulating the expression level of αkg. In some embodiments, the lead poisoning may be chronic lead poisoning. The invention has the following beneficial effects: The invention discovers that glutamine has obvious protection effect on abnormal nerve behavior and tissue pathological damage of lead-poisoned mice. Current drugs