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Polyprezinc | Prevent intestinal radiation damage

Polyprezinc | Prevent intestinal radiation damage

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-02
  • Views:0

(Summary description)

Polyprezinc | Prevent intestinal radiation damage

(Summary description)

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-02
  • Views:0
Information

  Preface

  Radiation therapy plays a vital role in cancer treatment and can improve the survival rate of patients. Radiation gastrointestinal disease is the most common complication in the treatment of malignant tumors of the abdomen and pelvis, which greatly reduces the quality of life of patients. Modern radiotherapy methods include intensity modulated radiotherapy and proton therapy, which can significantly reduce the toxicity of radiotherapy. Amifostine is recommended as a drug to prevent severe radiotherapy-induced toxicity and is the only radioprotectant approved by the US FDA. However, the daily use of Amifostine is limited due to its blood and gastrointestinal toxicity.

  Polyprezinc (PZ) is a chelate composed of zinc ions and L-carnosine, which is widely used clinically to treat gastric ulcers. Studies have shown that Polyprezinc has the effects of anti-oxidation and scavenging free radicals, and has a significant effect on acute radiation proctitis. At the same time, it also has a certain anti-inflammatory effect on inflammation caused by radiation. This study explored the protective effect of polyprezinc on the intestinal tract of mice exposed to radiation, which is of great significance for preventing radiation damage.

  1 Materials and methods

  1.1 Animal models and reagents

  "Male C57BL/6J mice (8 weeks old, weight approximately 20g). Breed in an environment with a temperature of 22±0.5°C and a humidity of 50%±5% with a 12-hour light/dark cycle. The mice drank drinking water supplemented with polyprezinc (100 mg/kg body weight). The mice were irradiated with a dose rate of ~200cGy/min, and a 150kvpx ray device was used for dosimetry. The probe was connected to the electrometer system close to the target.

  1.2 The radioprotective effect of polyprezinc on normal intestines

  "Before the experiment, polyprezinc was pretreated for 2h, and the imaging examination was performed with sodium sulphamidate (100mg/mL). In order to study the best time to administer polyprezinc for the protection of normal intestines, the established animal model was used to measure the survival rate of intestinal stem cells after ionizing radiation (IR) (such as number of glands/cross-section). The mice were divided into three groups: Group A: IR group; Group B: PZ pretreatment 2h before IR; Group C: PZ pretreatment 2h after IR (n=3/group). Mice were irradiated with 15 Gy whole body (TBI). Three days after the radiation, the mice were injected with pentobarbital (200 mg/kg) into the abdominal cavity and sacrificed. The duodenum, jejunum and ileum were taken, fixed, and stained with hematoxylin and eosin. Count viable crypts with ≥10 cells on each cross section under a microscope. The mice were divided into two groups: 2h before IR PZ pretreatment group [PZ(+) group] and drinking water without PZ group [PZ(-) group]. The specimens were collected for pathological evaluation and fixed in 10% neutral formalin buffer. All slides were stained by H&E and checked by light microscope. To evaluate the radiation protection effect of PZ on mice. To explore the inhibitory effect of PZ on IR-induced apoptosis of normal small intestine cells, mice received 2Gy TBI at 0, 4, and 8 hours after IR. Take the duodenum, jejunum, ileum, and rectum for pathological evaluation. Apoptotic cells were defined as epithelial cells containing apoptotic fragments in HE stained tissue sections. In addition, the proportion of apoptotic cells in each crypt was also analyzed to determine the apoptotic index. The location of apoptotic cells is determined by the number starting from the bottom of the crypt cell.

  1.3 Statistical analysis

  The data is expressed as an average value. Statistical analysis of the differences between the two or three groups. The parameter data of the two groups were analyzed using unpaired two-tailed F test and two-tailed Student’s t test. The three groups of parameter data were subjected to Bartlett test and one-way analysis of variance. When a significant difference between the three groups was observed, the Tukey-Kramer method was used for multiple comparisons. In addition, a 5% risk is defined as a significant difference between the two groups. Statistical analysis uses StatMate-IV software program. P<0.05 has a significant difference.

  2 Results and analysis

  2.1 The cytoprotective effect of polyprezinc before radiation is better to study the effect of polyprezinc on the survival of intestinal crypts after 15Gy TBI. The results show that polyprezinc can significantly reduce the apoptosis of stem cells in the duodenum, jejunum and ileum crypts induced by radiation. In addition, polyprezinc pretreatment can protect crypt cells from TBI damage, and compared with mice pretreated with PZ after IR, the number of crypt cells that survived in mice pretreated with PZ before IR increase. The best time for PZ administration is before or after 15 Gy systemic IR. PZ treatment increased the number of surviving intestinal crypts in the normal intestine. Compared with what was observed after IR, oral administration of PZ before IR had a significant radioprotective effect on intestinal crypt cells. PZ: Polyprezinc; IR: ionizing radiation.

  2.2 Polyprezinc significantly reduces the apoptosis index

  The average number of live bowel crypts in groups A, B and C were 20.2, 24.1, and 39.8 in the duodenum, respectively (P=0.04), and the ileum was 43, 51.3, and 66.1 (P=0.02), respectively (Figure 1). In addition, according to the multiple comparison test method, the duodenum and ileum of groups A and C are significantly different. Compared with mice pretreated with PZ after IR, mice pretreated with PZ showed more active intestinal stem cells in the crypts.

  According to the above data, pre-treated with PZ 2h before IR, apoptotic cells can be seen in pathological results.

  The cells were stained with hematoxylin and eosin after 4 hours of irradiation. At 4 hours after 15 Gy whole body irradiation, intestinal crypt cells containing apoptotic (micronucleus) bodies in the pathological results of hematoxylin and eosin staining were defined as apoptotic cells (arrow; scale bar, 50μm).

  The number of apoptotic cells in the small intestine reaches a peak 8h after IR. PZ pretreatment can protect normal intestinal cells from apoptosis caused by IR. The apoptosis index of duodenum, jejunum and ileum in PZ(-) group were 0.056, 0.106 and 0.084, respectively. The apoptosis index of duodenum, jejunum and ileum in the PZ(+) group were 0.022, 0.044 and 0.052, respectively. PZ has the effect of reducing cell apoptosis in duodenum and jejunum, but has no obvious effect on ilium. The P values ​​of duodenum, jejunum and ileum between PZ(+) and PZ(-) groups were 0.07, 0.01 and 0.12, respectively. Figure 3 (A) Continuous changes in the apoptosis index of duodenal cells; (B) jejunum and (C) ileum after 2 Gy irradiation at different times (0, 4 and 8h). PZ can reduce cell apoptosis in various parts and time points of the small intestine. PZ: Polyprezinc.

  The high frequency of apoptosis is in the lower part of each crypt in the intestine. Mice pretreated with PZ had fewer apoptotic cells in each crypt.

  Hematoxylin and eosin stained tissue (magnification, x20) shows the location of apoptotic cells. The location of apoptosis is determined. Apoptosis index of each part of crypt. 4h after irradiation, an increase in the incidence of apoptosis was observed at the bottom of the crypt axis from (A) duodenum, (B) jejunum and (C) ileum. PZ: Polyprezinc.

  Discuss

  Polyprezinc can significantly reduce the apoptosis of crypt stem cells in the duodenum, jejunum and ileum induced by radiation, and protect the crypt cells from TBI damage. The cytoprotective effect is better when taken before radiation. At the same time, polyprezinc significantly reduces the apoptosis index. Relaisen (Polyprezinc particles) has a significant protective effect on normal intestinal tissue apoptosis induced by ionizing radiation (IR), can prevent the death of intestinal stem cells caused by radiation, reduce radiotherapy-related intestinal toxicity, and greatly improve the patient’s Quality of life is the new gospel for cancer patients.

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Jilin Province Great Great Pharmaceutical Co. LTD
Jilin Province Great Great Pharmaceutical Co. LTD
Jilin Province Great Great Pharmaceutical Co. LTD
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