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Purpose Dysgeusia 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. Methods This 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. Results From 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). Conclusion There 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.

BACKGROUND Helicobacter pylori (H. pylori) infection is a worldwide problem with increasing burden on the health sector due to its increasing rate of resistance. The conventional triple therapy (TT) is becoming obsolete with a high failure rate of eradication, necessitating the need for better alternatives or regimens. AIM To investigate H. pylori eradication rate of TT vs modified bismuth quadruple therapy. METHODS Ninety-two patients with dyspepsia symptoms and positive 13C-urea breath test were randomly assigned to two groups. The first group (control group) was treated for 14 d using standard TT protocol: Esomeprazole (40 mg twice daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily). On the other hand, the second group was prescribed a 10-d course of modified bismuth quadruple therapy fortified with zinc carnosine: TT in addition to bismuth subcitrate (240 mg twice daily) and zinc carnosine (75 mg twice daily). A repeated 13C-urea breath test was done 4 wk after the completion of the eradication therapy. RESULTS Among the 92 subjects, 67.4% were males and 32.6% were females. There were no differences in demographic characteristics (age, body mass index, smoking history, previous antibiotics use and ethnicity) between the modified bismuth quadruple therapy group and TT group. The eradication rate was higher [93.5% (43/46)] in the modified bismuth quadruple therapy group compared to 69.6% (32/46) in the standard TT group (P = 0.003). Of the tested predictor variables, only nationality, smoking and therapy type were statistically significant. Besides dizziness, which was recorded in modified bismuth quadruple therapy group, there were no significant differences in side effects between the two groups. CONCLUSION Ten days of modified bismuth quadruple therapy fortified with zinc carnosine is superior to 14 d of conventional TT in eradicating H. pylori infection, with no additional significant adverse events.

Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.

Background Zinc plays an important role in appetite regulation. l-Carnosine, an endogenous dipeptide, may also regulate eating behavior via its histaminergic and antiglutamatergic properties. Polaprezinc (zinc–l-carnosine complex) is a medication for gastric ulcers. A small case series reported successful treatment of binge eating with add-on polaprezinc. Methods This was an open trial of add-on polaprezinc in patients with binge eating disorder (BED; n = 22) or bulimia nervosa (BN; n = 7) receiving antidepressants. A 4-week baseline period was followed by a 16-week polaprezinc treatment at 150 mg/d (containing 34 mg zinc and 116 mg l-carnosine) in addition to ongoing psychotropic medications. We also assessed their zinc status via a laboratory index and zinc deficiency–related symptoms. Results At the study end, both conditions showed a significant reduction in the 4-week frequency of combined objective and subjective binge eating episodes, the 4-week frequency of days when at least 1 such episode occurred (only in BED), several aspects of eating disorder psychopathology (rated by the Eating Disorder Examination–Questionnaire), and comorbid depressive symptoms (rated by the 16-item Quick Inventory of Depressive Symptomatology [Self-Report]). Serum copper/zinc ratio decreased from 1.4 to 1.1 on average in both conditions. All patients had multiple zinc deficiency–related symptoms at baseline that substantially improved after polaprezinc treatment. Overall, the effectiveness of polaprezinc was greater in BED patients than in BN patients, with minor adverse effects. Conclusions These findings offer preliminary evidence for the effectiveness of polaprezinc in treating BED and BN and suggest the involvement of zinc deficiency in these conditions.

Supplemental Digital Content is available in the text., Goals: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. Background: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. Study: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. Results: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). Conclusion: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Xue Gao,1,* Mohammed A Al-Baadani,2,* Minjie Wu,1 Ningyang Tong,1 Xinkun Shen,2 Xi Ding,1 Jinsong Liu2 1Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325016, People’s Republic of China; 2School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinkun ShenSchool and Hospital of Stomatology, Wenzhou Medical University, 268# Xueyuan West Road, Lucheng District, Wenzhou City, 325000, People’s Republic of ChinaTel +86-577-88066010Email 20111902015@cqu.edu.cnXi DingDepartment of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou City, 325016, People’s Republic of ChinaTel +86-577-55579913Email dingxi@wzhospital.cnBackground: Compared with the healthy condition, osteoporotic bone defects are often accompanied by poor osteogenesis and excessive reactive oxygen species (ROS), which pose serious challenges to bone augmentation and repair by normal resorbable guided bone regeneration (GBR) membrane.Purpose: Polaprezinc (PZ) was loaded into polycaprolactone/gelatin (PG) hybrid electrospun nanofibers to fabricate a GBR membrane with antioxidant and osteogenesis ability.Methods: A series of physicochemical characterization were performed by scanning electron microscopy, Fourier-transform infrared spectroscopy, and water contact angle measurement. In addition to membrane degradation and PZ release detection, membranes were tested for cell viability, differentiation, and protein expression in MC3T3-E1 cells by CCK8, alkaline phosphatase activity, mineralization, and Western blotting assays. The membrane osteogenic capacity in cranial bone defects was studied by micro-CT in vivo.Results: PZ was successfully doped into the PCL/GEL nanofibers to form a hydrophilic GBR membrane. The cumulative release of PZ was closely related to the membrane degradation behavior. PG/0.4%PZ membranes produced the best protective effect on cell proliferation/differentiation under oxidative stress microenvironment; however, the PG/0.8%PZ membrane was cytotoxic. Western blotting demonstrated that the PZ-loaded membrane upregulated the Nrf2/HO-1/SOD1 signaling molecules in a concentration-dependent manner. In addition, micro-CT results showed an abundant formation of new bones in the PG/0.4%PZ group compared to the PG group.Conclusion: PZ-loaded degradable PG membranes (especially PG/0.4%PZ) have great potential to accelerate bone regeneration in oxidative stress-related diseases.Keywords: electrospun membrane, polaprezinc, antioxidant, osteogenesis, osteoporosis

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on zinc l-carnosine as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of zinc for use in food supplements. The NF is produced by chemical synthesis and is proposed to be used in food supplements as a source of zinc. The target population proposed by the applicant is individuals above the age of 12, excluding pregnant and lactating women. The NF which is the subject of the application is a chelate-complex, formed between Zn2+ and l-carnosine and is present as a mixture of a monomer and a dimer. The material is a powder with particulate nature and is insoluble in water at neutral pH. No relevant data using an existing zinc source as comparator have been made available by the applicant and the actual bioavailability of the zinc provided by the NF at the proposed use levels remains uncharacterised. Owing to the lack of a correct characterisation of the fraction of small particles, including nanoparticles of the NF, the Panel is not in the position to evaluate specification limits for the size of the constituent particles in the NF. Owing to the lack of information on the size distribution and the physico-chemical properties of the particles constituting the NF, the Panel is not in the position to confirm whether the ADME studies and the toxicological studies provided by the applicant are appropriate to assess the safety of the NF. The Panel concludes that the NF is absorbed and provides zinc, but as it is in an insufficiently characterised particulate form, its safety has not been established and the bioavailability has not been determined.

The present study described the chemical and biological properties of zinc complex of L-carnosine (L-CAZ; generic name, polaprezinc; chemical name, catena-(S)-[µ-[N(α)-(3-aminopropionyl) histidinato (2-) N1, N2, O: N(τ)]-zinc], molecular formula, C(9)H(14)N(4)O(3)Zn; molecular weight, 291.6404; CAS registry number, 107667-60-7). Characterized as a white or yellowish white crystalline powder, this drug is insoluble in glacial acetic acid and almost insoluble in water, methanol, ethanol and ether. It is soluble in dilute hydrochloric acid, dilute nitric acid and sodium hydroxide solution, and its melting point is 260-270˚C. Polaprezinc is an anti-ulcer drug that was jointly studied and developed by Hamari Chemicals Co., Ltd. and Zeria Pharmaceutical Co., Ltd., and was first approved in Japan in 1994. This review article summarizes the research advances of polaprezinc, including the patents, preparations, synthetic routes, pharmacokinetics, pharmacological effects and application in clinical research.

Background: Quadruple therapy with polaprezinc provided an alternative to Helicobacter pylori eradication; however, the effect on gut microbiota remains uncertain. This study aims to identify whether polaprezinc-containing quadruple therapy causes adverse microbiota effects among asymptomatic adults, compared with bismuth therapy. Methods: This was a randomized control trial. One hundred asymptomatic H. pylori-infected adults were randomly (1:1) assigned to two treatment groups (polaprezinc-containing therapy, PQT; or bismuth-containing therapy, BQT). Fecal samples were collected from subjects before and 4–8 weeks after therapy. Samples were sequenced for the V4 regions of the 16S rRNA gene. Results: The relative abundance of the three dominant bacterial phyla (Bacteroidota, Firmicutes, and Proteobacteria) accounted for more than 95% of each treatment group. The alpha diversity between eradications that succeeded and those that failed had no significant difference (p > 0.05). After successful eradication, the alpha diversity in the BQT group decreased in comparison with the baseline (p < 0.05). Subjects who were successfully eradicated by BQT showed considerably lower alpha diversity indices than those of the PQT at follow-up (p < 0.05). The abundance of Parasutterella in subjects who were successfully eradicated by PQT was four times greater than that of BQT (q < 0.05). Conclusion: A 14-day PQT may be superior to BQT in maintaining short-term gut microbiota homeostasis after H. pylori treatment. Our findings preliminarily provide evidence of the short-term impacts of the gut microbiota after PQT treatment of H. pylori infection.

Aim: The aim of the present study is to investigate the effect of long-term zinc supplementation, which is important for the activation of various enzymes that contribute to antioxidant and antifibrotic activities, on the improvement of serum fibrotic markers in patients with autoimmune hepatitis (AIH). Methods: A total of 38 patients with AIH under regular treatment at our hospital who provided their consent for being treated with polaprezinc (75 mg twice daily) were included and classified into 2 groups: the patients with zinc elevation (n = 27) and the patients without zinc elevation (n = 11). Serum biomarker of fibrosis, protein expression levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were evaluated. Results: A significant difference was found between the variability of serum procollagen type Ⅲ and collagen type Ⅳ-7S between the 2 groups before and after zinc administration for more than 24 months (p = 0.043 and p = 0.049). In the patients with zinc elevation, no significant changes were found in collagenase (MMP-1 and MMP-13) before and after zinc administration, whereas a significant increase in the expression of gelatinase (MMP-2 and MMP-9) was found after administration (p = 0.021 and p = 0.005). As for the relative ratio of MMPs to TIMPs, only MMP-9 to TIMP-1 showed a significant increase (p = 0.004). Conclusions: Long-term treatment with polaprezinc has been demonstrated to safely improve serum fibrosis indices through increases in MMP-2/-9 and MMP-9/TIMP-1 and is expected to be well combined with direct antifibrotic therapies such as molecularly targeted agents.

Carbohydrate antigen 19-9 (CA 19-9) is a well-known tumor marker of adenocarcinoma (reference range, 37 U/mL). It can also be used, together with computed tomography, to monitor responses and resistance to chemotherapy in cancer patients. False elevation of CA 19-9 levels is often seen in conditions such as biliary tract obstruction and cholangitis. However, whether medication might induce false elevation of CA 19-9 levels has not yet been reported. A 74-year-old man was treated with third-line CPT-11 (irinotecan) plus panitumumab for stage IV cancer of the ascending colon. The patient developed chemotherapy-induced dysgeusia and was treated with polaprezinc. After polaprezinc administration, his CA 19-9 levels gradually increased from 18.9 to 1,699.4 U/mL. He developed deep vein thrombosis (DVT), although it was not associated with progressive disease or metastasis. Upon discontinuation of polaprezinc, CA 19-9 levels gradually decreased. This case demonstrates that polaprezinc may not only induce false elevation of CA 19-9 levels but also cause development of DVT induced by increased CA 19-9 levels, both of which are very rare events.

IntroductionLung cancer (LC) is highly prevalent worldwide, with elevated mortality. In this population, taste and smell alterations (TSAs) are frequent but overlooked symptoms. The absence of effective therapeutic strategies and evidence-based guidelines constrain TSAs’ early recognition, prevention and treatment (Tx), promoting cancer-related malnutrition and jeopardizing survival outcomes and quality of life.ObjectivesTo systematically review the literature on TSAs in LC patients, understand the physiopathology, identify potential preventive and Tx strategies and to further encourage research in this area.MethodsLiterature search on English language articles indexed to PubMed, CINALH, SCOPUS and Web of Science using MeSH terms “Lung neoplasms”,”Dysgeusia”, “Olfaction Disorders”, “Carcinoma, Small Cell”,”Carcinoma, Non- Small-Cell Lung “Adenocarcinoma of Lung”,”Carcinoma, Large Cell”, and non-MeSH terms “Parageusia”, “Altered Taste”, “Smell Disorder”, “Paraosmia”, “Dysosmia”,”Lung Cancer” and “Oat Cell Carcinoma”.ResultsThirty-four articles were reviewed. TSAs may follow the diagnosis of LC or develop during cancer Tx. The estimated prevalence of self-reported dysgeusia is 35-38% in treatment-naïve LC patients, and 35-69% in those undergoing Tx, based on studies involving LC patients only.One prospective pilot trial and 1 RCT demonstrated a clinically significant benefit in combining flavor enhancement, smell and taste training and individualized nutritional counselling; a systematic review, 1 RCT and 1 retrospective study favored using intravenous or oral zinc-based solutions (150mg 2-3 times a day) for the prevention and Tx of chemotherapy (CT) and radiotherapy (RT) -induced mucositis and subsequent dysgeusia.ConclusionsThis is the first review on dysgeusia and dysosmia in LC patients to our knowledge. We propose combining taste and smell training, personalized dietary counselling and flavor enhancement with oral zinc-based solutions (150mg, 2-3 times a day) during CT and/or RT in this population, in order to prevent and help ameliorate Tx-induced dysgeusia and mucositis. However due to study heterogeneity, the results should be interpreted with caution. Developing standardized TSA measurement tools and performing prospective randomized controlled trials to evaluate their effect are warranted.

The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is currently no effective antiviral drug or vaccine against the virus. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein–protein interactions between ASFV and swine were curated by integration of protein–protein interactions from multiple sources. Thirty-eight swine proteins were observed to interact with ASFVs and were defined as ASFV-interacting swine proteins. The ASFV-interacting swine proteins were found to play a central role in the swine protein–protein interaction network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of ASFV-interacting swine proteins also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted ASFV-interacting swine proteins and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on ASFV-interacting swine proteins were identified, such as Polaprezinc and Geldanamycin. Structural modeling and molecular dynamics simulation showed that Geldanamycin could bind with swine HSP90AB1 stably. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.

Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose–response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 µg/dL (95% confidence interval: 5.46, 12.70; heterogeneity: I 2 = 0.61%) compared to the placebo. A significant dose–response relationship was confirmed (p < 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose–response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 µg/dL, and 150 mg for 70 µg/dL or more.

To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of

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.

Cadmium is a toxic metal contained in food, water and the atmosphere, and exposure to cadmium can cause respiratory diseases in humans. Various health problems caused by cadmium result from oxidative stress-dependent cellular injury. Metallothioneins are intracellular, cysteine-rich, metal-binding proteins that have a detoxifying action on heavy metals such as cadmium in various organs. In addition, expression of metallothioneins is induced by metals with low biological toxicity, such as zinc. Therefore, in this study we examined whether polaprezinc, a chelate compound consisting of carnosine and zinc, can suppress cadmium-induced lung epithelial cell death. We found that cell viability markers (intracellular ATP levels and mitochondrial activity) and cytotoxicity (lactate dehydrogenase release) were decreased and increased, respectively by cadmium treatment; however, polaprezinc significantly reversed these changes. Moreover, cadmium-dependent endoplasmic reticulum stress responses were suppressed by polaprezinc treatment. We then examined the protective mechanisms of polaprezinc, focusing on oxidative stress. Cadmium induced the production of reactive oxygen species (ROS) in A549 cells in a dose-dependent manner and polaprezinc significantly suppressed this cadmium-induced ROS production. Finally, we examined whether polaprezinc exerts an antioxidative action by inducing metallothioneins. We found that polaprezinc dose-dependently induced metallothioneins using real-time RT-PCR, ELISA, and western blotting analyses. These results indicate that polaprezinc can suppress cadmium-induced lung epithelial cell death and oxidative stress by inducing metallothioneins. We therefore suggest that polaprezinc may have therapeutic effects against respiratory diseases, such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level

The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is no effective antiviral drug or vaccine against the virus until now. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein-protein interactions (PPIs) between ASFV and swine were curated by integration of PPIs from multiple sources. Thirty-two swine proteins were observed to interact with ASFVs and were defined as AIPs. They were found to play a central role in the swine PPI network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of AIPs also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted AIPs and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on AIPs were identified, such as Polaprezinc. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.

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

Treatment and prevention methods for non-steroidal anti-inflammatory drug-induced enteropathy have not yet been established. We tested the preventive effects of s-pantoprazole sodium trihydrate (PAN), polaprezinc (PZ), and probiotics on an indomethacin (Indo)-induced small intestinal injury in a rat model. Rats were randomised into 6 groups to receive: normal saline (control), Indo (6 mg/kg), PZ plus Indo, PAN plus Indo, or probiotics plus Indo (at 108and 109cfu/head) for 2 weeks. We measured body weight, food intake, severity of small intestinal damage, haemoglobin (Hb) levels in the small intestinal fluid, intestinal inflammatory cytokines, and a few groups of faecal bacteria. The experimental groups were found to have the following survival rates: 0% for the Indo, PZ, and PAN groups; 50% for both probiotic groups; and 100% for control. Treatment with probiotics of different concentrations reduced small intestinal lesion scores and intestinal fluid Hb as compared with the Indo group, while these parameters did not reduce in the PZ and PAN groups. The anti-inflammatory marker interleukin 10 increased in both probiotic groups. Analysis of a few groups of faecal bacteria revealed that Indo-induced a significant increase in Gram-negative bacteria and decreases in Bifidobacterium and Lactobacillus. Similar changes were also observed in the PZ and PAN groups. However, opposite effects were found in both probiotic groups. The use of probiotics appeared to be beneficial in preventing Indo-induced chronic small intestinal injury.

Zinc-L-carnosine (ZnC), also called polaprezinc known as PepZin GI™, is a chelated compound that contains L-carnosine and zinc. It is a relatively new molecule and has been associated with multiple health benefits. There are several studies that support ZnC’s benefits in restoring the gastric lining, healing other parts of the gastrointestinal (GI) tract, improving taste disorders, improving GI disorders, and enhancing skin and liver. Oral mucositis is a common complication of cytotoxic radiotherapy and/or chemotherapy. It occurs in almost every person with head and neck cancer who receive radiotherapy. It is often overlooked because it is not considered life threatening. However, mucositis often leads to a decreased quality of life and cessation of treatment, ultimately decreasing positive outcomes. Therefore, solutions to address it should be considered. The primary mechanisms of action are thought to be localized and related to ZnC’s anti-inflammatory and antioxidant functions. Therefore, the purpose of this review is to discuss the research related to ZnC and to explore its benefits, especially in the management of conditions related to damaged epithelial cells, such as oral mucositis. Evidence supports the safety and efficacy of ZnC for the maintenance, prevention, and treatment of the mucosal lining and other epithelial tissues. The research supports its use for gastric ulcers (approved in Japan) and conditions of the upper GI and suggests other applications, particularly for oral mucositis.

Background/aim Dysgeusia is one of the adverse events frequently affecting patients undergoing cancer chemotherapy. Dysgeusia-induced anorexia could decrease patient's quality of life. The present study was designed to determine whether the zinc-containing compound polaprezinc improves chemotherapy-induced dysgeusia. Patients and methods The incidence of grade 2 dysgeusia was assessed in 634 patients receiving cancer chemotherapy in outpatient settings during January 2013 and June 2017. Polaprezinc was administered to patients showing grade 2 dysgeusia and the effect was compared with that in patients subjected to follow-up observation. Results Grade 2 dysgeusia appeared in 80 patients (12.6%), in whom pancreatic cancer and treatment with fluoropyrimidines were significant risks for dysgeusia. Polaprezinc, when administered to patients with grade 2 dysgeusia, significantly shortened the duration of dysgeusia compared with that in the follow-up observation group. Subgroup analysis indicated that polaprezinc was less effective in patients with pancreatic cancer, those receiving gemcitabine, or those whose age was 65 year-old and over. Conclusion Chemotherapy-induced dysgeusia occurred with high frequency in patients with pancreatic cancer or in those receiving fluoropyrimidines. Polaprezinc was highly effective in improving the symptom of dysgeusia, except for patients with pancreatic cancer, those receiving gemcitabine and the elderly.

Objective To investigate the effects of polaprezinc (PZ) on cyclophosphamide (CTX)- or cisplatin (DDP)-induced gastric mucosal injury and on a rat model of neurotransmitter-mediated vomiting. Methods Sprague–Dawley rats were divided at random into Control, CTX, DDP, PZ+CTX, and PZ+DDP groups. After 20 days, brain tissues and sera were analyzed for the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and nuclear factor kappa B (NF-κB). Hematoxylin and eosin-stained sections of stomach, intestine, and brain tissues were examined using light microscopy. Results The levels of DA, 5-HT, and NF-κB in brain and serum samples of rats treated with CTX or DDP were significantly increased compared with those of rats in the Control group. There was a significant decrease in these values in the PZ group. Moreover, PZ reduced damage to brain tissue caused by CTX or DDP. Conclusions PZ decreased the levels of DA, 5-HT, and NF-κB in blood and brain tissues caused by CTX or DDP and reduced the chemotherapy-induced damage to the small intestine, stomach, and brain. These findings can be translated to the clinic to enhance the efficacy and safety of chemotherapy.

Background/aim Polaprezinc suspension in sodium alginate (PZ-AG) reduces the incidence and severity of oral mucositis in adult patients receiving radiotherapy or high-dose chemotherapy. In the present study, the prophylactic effect of PZ-AG against oral mucositis was assessed in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). Patients and methods Data of 16 children who underwent HSCT during a period between January 2010 and December 2017 were obtained from medical records and they were retrospectively analyzed. Oral mucositis was evaluated by the WHO scale. Results Six (37.5%) of 16 children refused to take PZ-AG in a preliminary assessment and they were pretreated with azulene gargle. The remaining 10 (62.5%) patients were pretreated with PZ-AG for prevention of oral mucositis. Grade≥ 3 oral mucositis occurred in 5 (83.3%) of 6 patients receiving azulene gargle, but in 2 (20%) patients who took PZ-AG (p=0.035). The prevalence for the use of opioid analgesics was also significantly lower (30% vs. 100%, p=0.011), while the average duration of total parenteral nutrition use was significantly shorter (11.1 days vs. 24.3 days, p=0.016), in PZ-AG group than in azulene group. On the other hand, PZ-AG had no significant influence on the incidence of other adverse events, mean time to engraftment, or overall survival. Conclusion PZ-AG was found to be highly effective in preventing oral mucositis in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by HSCT, as in adult patients.

Zinc (Zn) is abundantly present in the brain, and accumulates in the synaptic vesicles. Synaptic Zn is released with neuronal excitation, and plays essential roles in learning and memory. Increasing evidence suggests that the disruption of Zn homeostasis is involved in various neurodegenerative diseases including Alzheimer’s disease, a vascular type of dementia, and prion diseases. Our and other numerous studies suggest that carnosine (β-alanyl histidine) is protective against these neurodegenerative diseases. Carnosine is an endogenous dipeptide abundantly present in the skeletal muscles and in the brain, and has numerous beneficial effects such as antioxidant, metal chelating, anti-crosslinking, and anti-glycation activities. The complex of carnosine and Zn, termed polaprezinc, is widely used for Zn supplementation therapy and for the treatment of ulcers. Here, we review the link between Zn and these neurodegenerative diseases, and focus on the neuroprotective effects of carnosine. We also discuss the carnosine level in various foodstuffs and beneficial effects of dietary supplementation of carnosine.

Heat shock proteins (HSPs) represent an important element in the body's defense against various damaging factors. The probably also play an important role in the pathogenesis and treatment of several diseases, including autoimmune pathology and neoplasms. Recently, several investigators have focused their attention on the involvement of the HSP70 protein family in the morbid process of inflammatory bowel diseases (IBD). The HSP70 family of is represented by two distinct forms of protein, the HSP72 protein (also known as the HSP70.1 protein), the expression of which is clearly increased in conditions of stress; and the HSP73 (or HSC73) protein, which manifests stable expression. HSP70 proteins are present in the colorectal epithelium. In patients with inflammatory bowel diseases, their expression in significantly increased during the active stage of the disease. In experimental studies, overexpression of HSP70 was found to prevent the development of inflammatory process in the large intestinal mucosa provoked by various damaging factors. In physiological conditions, various mechanisms are considered to be responsible for an increased expression of HSP70. One of them involves lymphocyte activity and the production of cytokines (mainly IL-2). Another suggested mechanism involves the presence of bacteria in the large intestine, including both physiological flora (Lactobacillus GG, Bacteroides fragilis) and pathogenic bacteria (Salmonella, Escherichia coli). HSP70 expression is probably also increased by physical activity. There is also a potential for pharmacological stimulation of HSP70 expression, linked (for example) to geranylgeranylacetone, polaprezinc and mesalazine. Thus, augmentation of HSP70 expression may become a new element in IBD therapy.

5-Fluorouracil (5-FU) has broadly been applied to treat colorectal cancer as one of the most effective chemotherapeutic agents. However, it frequently causes intestinal mucosal injury and related side effects, such as abdominal pain and diarrhoea, which limit the use of 5-FU in a clinic setting. Polaprezinc has gradually become known as a mucosal protective agent for the management of gastric ulcer. This study aimed to investigate the prophylactic efficacy of Polaprezinc administered orally against intestinal mucositis induced by 5-FU in mice on the condition that the antitumour effect could not be compromised. We induced intestinal mucositis in SPF-grade ICR mice with 5-FU, and evaluated intestinal damage in the absence or presence of Polaprezinc. We examined the score of diarrhoea and the loss of weight after the 5-FU treatment and assessed the integrity of villus and the proliferation of small intestine crypt cells by haematoxylin and eosin staining and PCNA immunohistochemical detection. The antitumour effect of 5-FU on colorectal cancer was assessed with or without Polaprezinc in a xenograft model. The result showed that Polaprezinc significantly reduced the elevated diarrhoea score and the body-weight loss caused by 5-FU abolished histological abnormality and crypt cell hypoproliferation in a dose-dependent manner, without affecting 5-FU efficacy on colon xenograft tumour in mice. We conclude that Polaprezinc could inhibit 5-FU-induced diarrhoea and alleviate the weight loss during 5-FU chemotherapy, as a possible candidate for treatment and prevention of intestinal mucositis, through protecting intestinal mucosa and improving the quality of life after chemotherapy.

The efficacy and safety of polaprezinc combined with triple therapy was compared with triple therapy alone in the eradication of Helicobacter pylori. A randomized, parallel-group, open-label, controlled, prospective multicenter study was conducted in 11 cities in China. Treatment-naive patients with H. pylori–associated gastritis were randomly assigned to one of three arms for a 14-day treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy alone. The rate of H. pylori eradication was the primary endpoint. Secondary endpoints were symptom improvement and lower incidence of adverse events. 303 patients completed the study– 106, 96, and 101 patients in Arms A, B, and C, respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P = 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C (61.4%) (P < 0.01), whereas there was no significant difference between Arms A and B (P = 0.62). All three groups reported significant symptom improvement at 7, 14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C (1.9%) (P = 0.02). There were no serious adverse events in any group. It appears that standard dose polaprezinc combined with triple therapy can significantly improve the H. pylori eradication rate, without an increase in toxicity.

Biological trace metals (bio-metals) such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are essential to life and health of humans, and the success of platinum (Pt) drugs in the cancer chemotherapy has rapidly grown interest in developing inorganic pharmaceutical agents (metallodrugs) in medicinal chemistry, that is, medicinal inorganic chemistry, using either biologically essential metals or other trace metals with pharmacological functions. Transition metal complexes with unique chemical structures may be useful alternatives to the drug available to address some of the incurable diseases. Over thousand years after ancient people practiced many types of inorganic compounds, modern development of metallopharmaceutics has been achieved by P. Ehrlich and his coworkers, who found arsenic-containing arsphenamine (As) and established the concept of chemotherapy in 1910. Since the year, a wide variety of metallodrugs have been developed by many researchers, and some of them are clinically used worldwide involving cisplatin (Pt), auranofin (Au), and polaprezinc (Zn). In this chapter, we emphasize that metal complexes are an expanding of interest in the research field of treatment of lifestyle diseases such as diabetes mellitus and several cancers. Especially, we would like to review the current state for the research of metal-based nonclinical medicines for treatment of cancer and diabetes mellitus.

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 Conclusions The results of the present study suggest that polaprezinc has an anti-inflammatory effect and improves cardiac function after AMI.

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.

Aims Polaprezinc (PZ), which consists of l -carnosine and zinc, is widely used to treat gastric ulcers. We compared the effects of PZ with those of rebamipide (RM) on the expression of inflammatory cytokines, antioxidants, growth factors, and heat shock proteins (HSP) in a rat model. Main methods Seventy Sprague–Dawley rats were randomly assigned to test groups according to the dose of PZ at 5, 10, or 30 mg/kg or RM at 10, 30, or 100 mg/kg. Next, we obtained ulcer indices from rats with ethanol-induced gastric mucosal damage. Western blot analysis was used to evaluate the expression of various target proteins. Key findings Pathological ulcer indices in the PZ and RM groups were significantly lower than those in the control group. The levels of inflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-8, and tumor necrosis factor α) decreased, whereas the levels of platelet-derived growth factor-B, vascular endothelial growth factor, and nerve growth factor significantly increased after PZ administration. Furthermore, the expression of antioxidants (superoxide dismutase 1 [SOD-1], SOD-2, heme oxygenase-1, glutathione S-transferase, peroxidredoxin-1, and peroxidredoxin-5) was significantly higher in the PZ group, and the levels of HSP 90, 70, 60, 47, 27, and 10 significantly increased with an increase in PZ dose. Significance In a rat model of ethanol-induced gastric mucosal damage, PZ administration ameliorated ethanol-induced mucosal injury and showed protective effects on the mucosa by reducing the levels of inflammatory cytokines and increasing the expression of antioxidant enzymes and growth factors. Furthermore, PZ showed cytoprotective effects by increasing the HSP levels.

Unconsciously caustic ingestion is one of the most common causes of serious esophageal strictures in children. The aim of this study is to determine the efficiency of polaprezinc in preventing stricture formation after corrosive esophageal burns (CEB); this was the first time it has been used to treat experimental CEB in rats. Twenty-four rats were divided into four groups, three of which received CEB by the instillation of 1 mL of 10% NaOH solution into their isolated esophageal segments for three minutes. Group C (control) was uninjured and untreated. Group B (esophageal burn) received CEB but were left untreated. Groups PT1 and PT2 had CEB and received 100 mg/kg/day and 200 mg/kg/day, respectively, of intraperitoneal polaprezinc treatment (PT) for the first two weeks, then oral PT for another two weeks. We assessed the treatment's efficiency of the treatment after the fourth week by evaluating the stenosis index (SI) and the histopathological damage score, determining tissue hydroxyproline content (HP), and measuring the weight of the rats before and after the experiment. Mean SI was statistically lower in the groups PT1 and PT2 when compared with Group B (p = 0.006, 0.004, respectively). HP levels were highest in Group B, but it was insignificant (P > 0.05). In terms of histopathological damage score, treatment groups demonstrated less collagen deposition, mucosal, and submucosal damage than both Group B (p = 0.01) and Group C (p = 0.02). Group PT1 and Group PT2 (P > 0.05) showed similar results, indicating the treatment's effectiveness was independent of dosage. Outside of Group C, weight gain was detected only in Group PT2, though it was statistically insignificant. In Group PT1, weight loss was lower than in Group B. Polaprezinc, with its antifibrotic, antioxidant, anti-inflammatory, wound-healing and antiapoptotic effects, was efficient in reducing stricture formation by decreasing HP levels and histopathologic damage, preventing stenosis, and weight gain in higher dosages in the treatment group.

Hepatic fibrosis is defined as a pathological process, and activation of hepatic stellate cells (HSCs) is believed to be the key event of liver fibrosis. Additionally, activated HSCs may participate in the formation of the tumor microenvironment. Polaprezinc, a protector of the gastric mucosa, has been recently demonstrated to be an inhibitor of liver fibrosis in a mouse model. Proliferation and colony formation assays were performed to determine the inhibitory effects of polaprezinc on the growth of LX‑2 and hepG2 cells. A migration assay was used to evaluate the change in mobility of LX‑2 cells and quantitative polymerase chain reaction was performed to detect the expression levels of key markers of fibrosis. Finally, a gene chip assay for polaprezinc‑treated hepG2 cells was performed to evaluate the effect of polaprezinc on the hepG2 gene expression profile. The proliferation assay indicated that polaprezinc may inhibit the LX‑2 cell proliferation and the migration assays confirmed the inhibition of mobility. The expression levels of fibrotic markers such as collagen I, fibronectin and α‑smooth muscle actin were downregulated following polaprezinc treatment. The proliferation activity of polaprezinc‑treated hepG2 cells was reduced and the gene chip assay indicated that series of gene expression changes associated with cancer migration, cell skeletal organization and proliferation had occurred. In conclusion, polaprezinc treatment mayinhibit the proliferation of hepatocellular carcinoma cells and reverse liver fibrosis by deactivating HSCs. The present findings suggest that polaprezinc provides a novel treatment for patients with gastritis complicated with cirrhosis.

We previously reported that oral ingestion of polaprezinc, a zinc-L-carnosine, suspended in sodium alginate solution prevents oral mucositis in patients receiving radiotherapy or high-dose chemotherapy. In the present study, we developed a novel preparation of polaprezinc and evaluated clinical effect of the lozenge preparation in patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The preparation contained 18.75 mg polaprezinc in a tablet and showed an excellent uniformity and stability up to 24 weeks after storage under room temperature. The incidence rate of grade ≥ 2 oral mucositis was 74 % in patients without premedication, whereas the rate was remarkably reduced in patients receiving the suspension (23 %) or lozenge (13 %) of polaprezinc (P

Objectives/Hypothesis: We examined the effect of zinc deficiency and supplementation on the expression of bitter taste receptor (TAS2R) and epithelial sodium ion channel (ENaC) genes on the tongue in rats. Study Design: Prospective animal study. Methods: A total of 36 male Sprague-Dawley rats (3 weeks old) were used. Twelve rats were fed a normal diet for 28 (n = 6) or 56 (n = 6) days, another 12 were fed a zinc-deficient diet for the same periods, and still another 12 were fed a zinc-deficient diet for 28 days and then administered zinc for a further 28 days. The epithelium of the circumvallate papillae was collected, and expression of the TAS2R40, TAS2R105, TAS2R107, TAS2R118, TAS2R121, TAS2R136, TAS2R140, and ENaC genes was examined by reverse transcriptase-polymerase chain reaction. Results: Gene expression frequency of TAS2R40 and TAS2R107 significantly decreased in rats fed a zinc-deficient diet, and frequency of TAS2R107 significantly increased following zinc administration. No changes were noted in expression of TAS2R105, TAS2R118, TAS2R121, or ENaC in zinc-deficient rats. Conclusions: Our findings suggest that zinc may affect gene expression for some TAS2Rs on the tongue in rats. Laryngoscope, 2012

Zinc is crucial for maintaining human body homeostasis and is one of the major components of hormones, signal molecules, and enzymes. Zinc deficiency is caused by insufficient uptake of zinc from food, or caused by malabsorption syndromes, increased gastrointestinal and urinary losses, and administration of various medications. In order to test whether oral zinc administration can successfully improve zinc deficiency-related alopecia, we treated five patients with zinc deficiency-related telogen effluvium with oral zinc administration in the form of polaprezinc (Promac®). In all patients, hair loss was cured or improved. The administration of zinc for zinc deficiency-related alopecia may recover appropriate activities of metalloenzymes, hedgehog signaling, and immunomodulation, all of which are required for normal control of hair growth cycle.

Author, Aims: Cirrhotic patients commonly have a liver zinc deficiency, which may aggravate liver fibrosis due to the lack of antioxidative effects of zinc. This study examined the ability of polaprezinc, N-(3-aminopropionyl)-Lhistidinato zinc, to prevent fibrosis in a rat model of thioacetamide (TAA)-induced hepatic fibrosis. Main methods: Liver cirrhosis was induced by orally administering TAA for 20 weeks. The rats were cotreated with one of the following for the last 10 weeks of TAA treatment: (1) polaprezinc (50 or 200 mg/kg/day); (2) L-carnosine (155 mg/kg/day),which contained equal amounts of L-carnosine as 200 mg/kg/day polaprezinc; (3) zinc sulfate (112 mg/kg/day) or (4) zinc-L-aspartic complex (317.8 mg/kg/day). Both zinc supplementations contained equal amounts of zinc as high-dose polaprezinc. Key findings: Hepatic zinc levels fell significantly in rats treated with TAA for 20 weeks. Cotreating with high-dose polaprezinc and zinc-L-aspartic complex for 10 weeks prevented hepatic zinc loss. Hepatic hydroxyproline and tissue inhibitor of metalloproteinases-1 (TIMP-1) were significantly higher in rats treated with TAA for 20 weeks than 10 weeks, whereas polaprezinc prevented changes in these fibrosis markers and reduced hepatic transforming growth factor-β1 protein concentration, macroscopic and histologic changes. TAA caused oxidative stress-related changes in the liver that were prevented by high-dose polaprezinc and partially by zinc-L-aspartic complex. Treatment with L-carnosine, low-dose polaprezinc or zinc sulfate for 10 weeks did not affect liver fibrosis progression or oxidative stress-related changes. Significance: Polaprezincmay prevent ongoing fibrosis by preventing zinc depletion, oxidative stress and fibrosis markers in cirrhotic livers.

Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

Purpose The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ−), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10th day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ−, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ−, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.

Aims We investigated the therapeutic effect of polaprezinc (PZ), N-(3-aminopropionyl)- l -histidinato zinc, in rats with experimentally-induced colitis by focusing on calcineurin (CN) inhibition. CN plays a crucial role in T-cell activation and cytokine gene expression and is targeted by immunosuppressants such as cyclosporine and FK506. Main methods Colitis was induced into male Wistar rats by trinitrobenzene sulfonic acid and was treated with intrarectally administered PZ. The inflammation was assessed by the macroscopic damage score, colon wet weight, and proinflammatory mediator expression by RT-PCR analysis. Protein expression of calcineurin and the activation of its substrate, the nuclear factor of activated T cells (NFAT) transcription factor, were also studied. Calcineurin inhibition by PZ was investigated in in vitro experiments using colonic mucosa, purified calcineurin enzyme, and Jurkat T cells. Key findings CN was activated in the colitic mucosa; PZ treatment inhibited CN activation, the expression of proinflammatory cytokines in the mucosa, and thereby ameliorated the experimental colitis in rats. In in vitro experiments, PZ inhibited CN activity, NFAT activation, interleukin-2 expression, and the growth of Jurkat T cells. In the effective concentrations, PZ did not affect cell viability. Significance Our results suggest that PZ can be used as an immunosuppressive agent for the treatment of colitis through its inhibitory effect on CN activity.

Zinc is often deficient in patients with liver cirrhosis, and treatment with zinc provides short-term improvement in protein metabolism. However, the long-term effects of zinc have not been fully clarified. The present study aimed to analyze the effect of zinc on the long-term clinical course, especially hepatocarcinogenesis, in type C liver cirrhosis. Am- ong patients with type C liver cirrhosis visiting our hospital between June 1998 and January 2009, th- ose with a serum albumin level ≤3.5 g/dL and a serum zinc level ≤70 μg (1.07 μmol)/dL were selected. Thirty-seven patients were randomly divided into 2 groups: group B (12 g/day branched-chain amino acid granules) and group BZ (same as group B plus 100 mg/day - 600 mg/day zinc sulfate or 150 mg/day - 225 mg/day polaprezinc). Multivariate analysis revealed that the administration of zinc was not a significant determinant, but pretreatment serum zinc levels (hazard ratio [HR], 0.921; 95% confidence interval [CI], 0.853–0.994) and serum zinc levels less than 80 μg (1.22 μmol)/dL 12 months after beginning this study (HR, 6.866; 95% CI, 1.399 - 33.707) were significant determinants of carcinogenesis and death. Serum albumin levels in patients whose serum zinc levels had not increased up to 80 μg/dL by the third year of this study were significantly lower (p = 0.023) than those of patients that had increased up to 80 μg/dL. Conclusions: In type C liver cirrhosis with zinc deficiency, administration of zinc does not improve cancer-free survival. However, serum zinc levels can predict outcomes in patients with type C liver cirrhosis. However, although zinc may play a role in hepatocarcinogenesis, the precise implications remain to be clarified.

Background and Aim: Contemporary medications used in the treatment of gastric ulcers involve the use of novel mucosal protective drugs. The present study aimed to investigate the gastroprotective effect of ginger extract and polaprezinc in a rat model of acetic acid-induced gastric ulcer. Methods: ‘Kissing’ ulcers were induced in male Sprague-Dawley rats by using 60% acetic acid. Rhizoma Zingiber officinale (ginger) extract (1.5–5 g/kg) or polaprezinc (30 and 60 mg/kg) was orally given to the animals once daily for three consecutive days after ulcer induction. All animals were killed on day 5 by an overdose of ketamine. Results: Both ginger extract and polaprezinc significantly reduce the gastric ulcer area in a dose-dependent manner, with concomitant attenuation of the elevated activities of xanthine oxidase and myeloperoxidase, as well as malondialdehyde level in the ulcerated mucosa. Nevertheless, only polaprezinc could restore the mucosal glutathione level. Polaprezinc also causes the overexpression of basic fibroblast growth factor, vascular endothelial growth factor and ornithine decarboxylase, whereas ginger extract only increases the expression of the two growth factors in the gastric mucosa. Furthermore, polaprezinc could consistently downregulate the protein expression of tumor necrosis factor (TNF)-α, interleukin-1β, macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant-2α that have been activated in the ulcerated tissues, whereas ginger extract mainly inhibits the expression of the chemokines and to some extent TNF-α. Conclusion: Ginger extract and polaprezinc both show anti-oxidation that consequently alleviates gastric mucosal damage and promotes ulcer healing, which together serve as effective mucosal protective agents.

Background: Nonsteroidal anti-inflammatory drugs frequently cause gastrointestinal (GI) injury. Zinc-l-carnosine has antioxidant, anti-inflammatory, mucosal protective, and healing properties in rodent models and in some human studies of GI injury. Hypothesis: The combination of zinc-l-carnosine and vitamin E attenuates aspirin-induced gastroduodenal mucosal injury. Animals: Eighteen healthy random-source Foxhound dogs. Methods: In this randomized, double-blinded, placebo-controlled study dogs were treated with placebo (n = 6; 0X group), 30 mg/30 IU (n = 6; 1X group), or 60 mg/60 IU (n = 6; 2X group) zinc-l-carnosine/vitamin E orally every 12 hours for 35 days. Between Day 7 and 35, GI mucosal lesions were induced with aspirin (25 mg/kg PO q8h). Mucosal injury lesions (hemorrhage, erosion, and ulcer) were assessed by gastroduodenoscopy on Days 14, 21, and 35 with a 12-point scoring scale. Results: At baseline (Day −1) gastroscopy scores were not significantly different between groups (mean ± SD: 0X, 4.4 ± 0.8; group 1X, 4.4 ± 0.6; group 2X, 4.2 ± 0.3; P= .55). Gastroscopy scores increased significantly in all groups between Day −1 and Days 14, 21, and 35 (P < .0001). On Day 35, gastroscopy scores were 29.2 ± 5.2 (0X), 27.3 ± 3.7 (1X), and 28.6 ± 3.3 (2X). Mean gastroscopy scores were not significantly different among treatment groups on any of the days (P= .61). Conclusions and Clinical Importance: Administration of the combination of zinc-l-carnosine and vitamin E at 1X or 2X dosing did not attenuate aspirin-induced gastroduodenal mucosal injury.

Aliment Pharmacol Ther 2010; 32: 1080–1090 Summary Background Hepatic encephalopathy has a negative effect on patient health-related quality of life (HRQOL). Zinc supplementation has been effective with regard to altered nitrogen metabolism. Aim To investigate the effectiveness of oral zinc supplementation on hepatic encephalopathy and HRQOL. Methods Seventy-nine cirrhotic patients with hepatic encephalopathy were randomized to receive 225 mg of polaprezinc in addition to standard therapies of a protein-restricted diet including branched-chain amino acid and lactulose, or to continue only standard therapies for 6 months. The change of HRQOL by Short Form-36, hepatic encephalopathy grade, laboratory parameters, and neuropsychological (NP) tests were compared at baseline and at 6 months. We also evaluated via multivariate analysis whether zinc supplementation and clinical variables correlated with the changes in physical component scale (PCS) and mental component scale (MCS) between the two visits. Results Zinc supplementation significantly improved the PCS (P = 0.04), but not the MCS (P = 0.95). Zinc supplementation significantly decreased hepatic encephalopathy grade and blood ammonia levels (P = 0.03 and P = 0.01), and improved Child-Pugh score and NP tests compared with standard therapy (P = 0.04 and P = 0.02). In multivariate analysis, zinc supplementation was significantly associated with improvement in PCS (P = 0.03), whereas it was not significantly associated with change in MCS (P = 0.98). Conclusion Zinc supplementation is effective in hepatic encephalopathy and consequently improves patients HRQOL.

J Oral Pathol Med (2010) 39: 617–623 Objective: To examine the effects of polaprezinc on morphologic change of the tongue epithelium and on cell cycle regulation of taste bud cells by using zinc-deficient rats, an animal model of taste disturbance. Methods: After 28 days of feeding with zinc-sufficient or -deficient diet, the rats fed a zinc-deficient diet were divided into four groups in which 0, 1, 3 and 10 mg/kg of polaprezinc were administered for 28 days with continuation of diet. Histopathological and morphological examinations of the tongue were carried out. Results: Parakeratosis was observed in all rats receiving the zinc-deficient diet and 1 mg/kg polaprezinc but not in rats receiving 3 and 10 mg/kg polaprezinc. The ratio of keratinizing epithelium in the outer and inner circumference were significantly increased from 9.6% and 11.3%, respectively, in zinc-sufficient rats to 36.9% and 32.9%, respectively, in zinc-deficient rats (P