Polaprezinc Group Research Articles

Multicenter, prospective, observational study of chemotherapy-induced dysgeusia in gastrointestinal cancer

PurposeDysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer.MethodsThis multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks.ResultsFrom February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were − 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045).ConclusionThere was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia.Trial registration.UMIN000039653. Date of registration: March 2, 2020.

Intrarectally administered polaprezinc attenuates the development of dextran sodium sulfate-induced ulcerative colitis in mice.

Polaprezinc (PZ), a chelate of zinc and L-carnosine, has been widely used in the treatment of gastric ulcers since 1994. In recent years, researchers have found PZ to have a beneficial effect on various experimentally induced models of colitis in mice. In the present study, 6% dextran sodium sulfate (DSS) was used to induce a model of ulcerative colitis (UC) in Institute of Cancer Research mice. The therapeutic effect and mechanism of PZ action in a model of UC was studied in order to provide an experimental basis for the clinical application of PZ in UC treatment. The effect of PZ on UC was evaluated in five groups of mice: A vehicle control only group, a DSS model control group (DSS, 6%), a validated treatment control group (DSS 6% + Mesalamine), a low-dose PZ treatment group (DSS 6% + PZ 60 mg/kg) and a high-dose PZ group (DSS 6% + PZ 120 mg/kg). After the animals were sacrificed, blood was collected and the serum levels of NF-κB and tumor necrosis factor-α (TNF-α) were measured. Changes in histology were observed by light microscopy. The protein levels of AKT, phosphorylated AKT and heat shock protein 70 (HSP70) were determined by western blot analysis. The results suggested that PZ reduced the DSS-induced increase in the inflammatory proteins TNF-α and NF-κB in the UC model. The high-dose of PZ also increased the HSP70 protein level, inhibited AKT phosphorylation in a DSS-induced UC animal model, and decreased white blood cell and neutrophil % counts compared to levels in an untreated DSS control group. Histopathology indicated that the mice of the DSS model group had irregular colonic villi, a large number of inflammatory cells and mucosal damage, whereas mice of the group treated with PZ had small intestinal villus morphology and their villi showed signs of recovery from the damage of UC. The results of the present study indicated that PZ significantly alleviates DSS-induced UC in mice, relieves diarrhea, and inhibits the phosphorylation of inflammatory factors and the inflammatory AKT signaling pathway.

Beneficial effect of polaprezinc on cardiac function post-myocardial infarction: A prospective and randomized clinical trial.

Background:Polaprezinc is clinically used for the treatment of gastric ulcers. It induces the mobilization of mesenchymal stem cells and the mRNA expression of insulin-like growth factor-1 in vascular endothelial cells in order to protect injured gastric tissue or skin.Methods:The current study population included 50 patients with primary acute myocardial infarction (AMI). After percutaneous coronary intervention, the subjects were randomly divided into 2 groups, namely, the nonpolaprezinc and polaprezinc groups. Peripheral blood and urinary samples were collected in a specific time to analyze zinc concentration, cardiac enzymes, and the levels of the inflammation marker interleukin-6. To evaluate the cardiac function, echocardiography was performed upon admission to the hospital and at 9 months post-AMI.Results:The urine and blood zinc levels of the polaprezinc group were higher compared with those of the non-polaprezinc group at 8 days after percutaneous coronary intervention. The mean interleukin-6/maximal creatine phosphokinase level was significantly reduced in the polaprezinc group (0.024 [0.003–0.066] vs. 0.076 [0.015–0.212], respectively; P = .045). In addition, echocardiography revealed that the ejection fraction of the nonpolaprezinc group was not significantly increased between day 3 and 9 months post-AMI (53 [49–60.8] vs. 59.5 [52–69.3], respectively; P = .015). However, a significant increase was detected in the ejection fraction of the polaprezinc group at the 2 time points (54 [51–57] vs. 62 [55–71], respectively; P < .01).Conclusions:The results of the present study suggest that polaprezinc has an anti-inflammatory effect and improves cardiac function after AMI.

Protective effect of polaprezinc on acute gastric mucosal injury in rats.

To explore the role of prostaglandin E2 (PGE2) and epidermal growth factor (EGF) in the protective effect of polaprezinc on acute gastric mucosal damage. Methods: A total of 30 male SD rats were randomly divided into 3 groups as follows: A blank group, a model group, and a polaprezinc group. The blank group was fed normally. As for the model group and the polaprezinc group, the rats were given 1 mL ethanol (intragastrical administration) first, then they were treated with vehicle (1 mL distilled water) or polaprezinc treatment (100 mg/kg) 1 h later. On the 3rd day, rats in each group were fasting for 24 h before gastric administration. After 2 h of gastric administration, 5 mL of intraperitoneal blood was collected, centrifuged and stored at -80 ℃ for the detection of EGF and PGE2. Gastric tissue was collected for anatomic and pathological assessment. Results: Polaprezinc reduced gastric mucosa injury in the polaprezinc group compared to the model group. Compared with the blank group, the levels of PGE2 and EGF in blood serum were significantly decreased in the model group and the polaprezinc group (P<0.05), while there was no significant difference between the model group and the polaprezinc group (P>0.05). Conclusion: Polaprezinc can provide effective protection for acute mucosal injury and the underlying mechanism is not directly related to PGE2 and EGF.

Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis.

Background: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Methods: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

Efficacy of zinc–carnosine chelate compound, Polaprezinc, enemas in patients with ulcerative colitis

Objectives. Ulcerative colitis (UC) is a chronic, relapsing and remitting intestinal inflammatory disorder. Zinc is known to be efficacious for the repair of damaged tissue and has been shown to protect against gastric ulceration. This study focused on Polaprezinc (PZ), N-(3-aminopropionyl)-L-histidinato zinc, which accelerates ulcer healing through actions such as prostaglandin-independent cytoprotection and antioxidative activity. Methods. In this randomized, placebo-controlled, investigator-blinded trial, 28 patients with active UC at The Jikei University Hospital were randomly divided into two groups: one treated with a 150 mg PZ enema (n = 18) and the other not treated with a PZ enema (n = 10). All patients received usual induction therapy. Clinical symptoms, endoscopic findings and histological findings were evaluated at entry and one week later. Results. In the PZ group, modified Matts' endoscopic scores were significantly improved after treatment compared to baseline in the rectum (p = 0.004), sigmoid colon (p = 0.03) and descending colon (p = 0.04). In the non-PZ group, scores were not significantly improved in the rectum (p = 0.14) and descending colon (p = 0.34), but were improved in the sigmoid colon (p = 0.04). In the PZ group, the Mayo scores at baseline and at Day 8 were 9.1 ± 1.6 and 5.8 ± 2.7 (p = 0.00004), respectively, and in the placebo group, the scores were 8.9 ± 1.7 and 7.4 ± 2.1 (p = 0.009), respectively. Clinical response or remission was significantly better in the PZ group (71%) than in the placebo group (10%). Conclusions. A zinc-carnosine chelate compound, PZ, enema may become a useful new add-on treatment to accelerate mucosal healing in UC.

Effects of L‐Carnosine and Its Zinc Complex (Polaprezinc) on Pressure Ulcer Healing

L-carnosine (CAR) is an endogenous dipeptide. We aimed to determine the effects of CAR and its zinc complex polaprezinc (PLZ) on pressure ulcer healing in institutionalized long-term care patients. This study was a nonrandomized controlled trial with a maximum 4-week follow-up. Forty-two patients with stage II-IV pressure ulcers for 4 or more weeks were allocated to 1 of 3 groups in order of recruitment: the control group (n = 14) was untreated, the PLZ group (n = 10) orally received 150 mg/d PLZ (containing 116 mg CAR and 34 mg zinc), and the CAR group (n = 18) orally received 116 mg/d CAR. Pressure ulcer severity was measured weekly using the Pressure Ulcer Scale for Healing (PUSH) score. At baseline, no significant differences were found among groups in demographic and nutrition parameters and pressure ulcer characteristics (severity, size, and staging). After 4 weeks, the rate of pressure ulcer healing, assessed by the mean weekly improvement in PUSH score, was significantly greater in the CAR (1.6 ± 0.2, P = .02) and PLZ groups (1.8 ± 0.2, P = .009) than in the control group (0.8 ± 0.2). The difference between the CAR and PLZ groups was not significant (P = .73). Actual dietary intakes over this period did not differ significantly among groups. Our results suggest that CAR and PLZ may almost equally accelerate pressure ulcer healing during 4 weeks. The results need confirmation by randomized controlled trials with larger sample sizes.

Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study

BackgroundTreatment of low-dose aspirin (LDA)-induced small-bowel injury has not been established. Polaprezinc, a chelate of zinc and L-carnosine, may be efficacious for such injury. We conducted a pilot randomized controlled study to investigate whether polaprezinc is effective against LDA-induced small-bowel injuries.MethodsConsecutive patients under long-term (>3 months) LDA treatment and who agreed to participate in our study underwent initial capsule endoscopy (CE). Patients with LDA-induced small-bowel injury apparent upon initial CE (n = 20) were randomized into a polaprezinc (150 mg/day for 4 weeks) group and a control (no polaprezinc treatment) group. All underwent follow-up CE after 4 weeks. Changes in the number and characteristics of small-bowel mucosal injuries were compared within and between the two groups.ResultsThe median number of reddened lesions and erosions/ulcers upon follow-up CE in the polaprezinc group significantly decreased (P < 0.05). However, there was no significant difference in the median number of reddened lesions and erosions/ulcers upon follow-up CE in the control group.ConclusionsCo-administration of polaprezinc may be effective against small-bowel mucosal injury associated with long-term LDA therapy.Trial registrationUMIN Clinical Trials Registry UMIN000003687.

Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer

Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health-related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L-carnosine), a gastric mucosal protective drug, on radiochemotherapy-induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response.

Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy.

We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori-colonized Mongolian gerbils. Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. In all H. pylori-inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). Polaprezinc inhibited H. pylori-associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils.