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Treatment of castration‐resistant prostate cancer (CRPC) is a long‐standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking androgen receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug‐tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up‐regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration‐resistant prostate cancer. [ABSTRACT FROM AUTHOR]

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. What's new?: Chemotherapy‐induced oral mucositis is a common, painful condition that can result in an inability to eat, affecting patient nutrition. In this multi‐institutional randomized controlled study, the authors investigated the ability of polaprezinc (PZ) lozenges to prevent oral mucositis associated with conditioning chemotherapy in patients undergoing hematopoietic stem cell transplantation (HSCT). PZ lozenges effectively prevented grade ≥2 oral mucositis associated with chemotherapy in about 22 percent of HSCT patients, with no impact on HSCT outcome. The lozenges did not prevent grade ≥3 mucositis. The findings indicate that PZ lozenges are effective against moderate oral mucositis in some patients. [ABSTRACT FROM AUTHOR]

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 <70 μg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6‐month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients. [ABSTRACT FROM AUTHOR]

Background The purpose of the present study was to determine whether polaprezinc suspension in sodium alginate (P-AG) reduces the irradiation period and time to discharge after completion of radiotherapy in patients with head and neck cancer. Methods The incidence and severity of oral mucositis, the irradiation period, and the time to discharge in patients who received radiotherapy with head and neck cancer were investigated retrospectively from the medical records. Results The incidence of grade 3 oral mucositis was significantly lower in the P-AG group than in the control group (16.5% vs 52.0%; p = .0003). P-AG also significantly reduced median duration of radiotherapy (hazard ratio [HR] = 0.557; 95% confidence interval [CI] = 0.357-0.871; p = .0149) and median time to discharge after completion of radiotherapy (HR = 0.604; 95% CI = 0.386-0.946; p = .028). Conclusion P-AG reduced the irradiation period and the time to discharge after completion of radiotherapy by preventing oral mucositis in patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1387-1392, 2016 [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs frequently cause gastrointestinal (GI) injury. Zinc--carnosine has antioxidant, anti-inflammatory, mucosal protective, and healing properties in rodent models and in some human studies of GI injury. The combination of zinc--carnosine and vitamin E attenuates aspirin-induced gastroduodenal mucosal injury. Eighteen healthy random-source Foxhound dogs. 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--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. 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). Administration of the combination of zinc--carnosine and vitamin E at 1X or 2X dosing did not attenuate aspirin-induced gastroduodenal mucosal injury. [ABSTRACT FROM AUTHOR]

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. '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. 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. 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. [ABSTRACT FROM AUTHOR]

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 < 0.001 and <0.01). This increase was reversed to 13.7% and 12.3% in rats that received 3 and 10 mg/kg polaprezinc in the outer circumference, respectively. Same phenomenon was seen in the inner circumference part, 13.0% and 10.8% ( P < 0.01), respectively. In addition, proliferating cell nuclear antigen-positive cells in the taste bud were significantly decreased from 75.5% in zinc-sufficient rats to 32.2% in zinc-deficient rats ( P < 0.001). This decrease was reversed to 70.3%, 83.1% and 81.2% in rats that received 1, 3 and 10 mg/kg polaprezinc, respectively. Conclusion: Polaprezinc improves parakeratosis and decreases taste bud cell proliferation caused by zinc deficiency. These effects may be involved in mechanisms underlying improvement of taste disorders in animal models. [ABSTRACT FROM AUTHOR]

Background and Aim: The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice. Methods: Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed. Results: MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-α, transforming growth factor-β1 and procollagen α1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late. Conclusion: These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of oral zinc supplementation (polaprezinc) for 24 weeks (34 mg/day zinc) on liver fibrosis in patients with advanced chronic liver disease. Methods: Various markers of liver fibrosis, and fibrogenic and fibrolytic enzyme activities were measured before and after zinc supplementation in 17 patients with early cirrhosis. Results: Serum zinc levels were decreased in the patients as compared with healthy controls. No side-effect was noted in any of the patients who received zinc supplementation. Serum levels of zinc increased by up to 156% over baseline levels in the group of patients who took oral zinc for 24 weeks. In patients whose serum zinc levels increased, the serum levels of type IV collagen and the activity of tissue inhibitors of metalloproteinase-1 (TIMP-1) were significantly reduced, but no such change was observed in the other groups of patients, and no other serum markers changed. Conclusion: These results suggest that oral zinc supplement therapy with polaprezinc is safe and may be a novel and useful strategy for antifibrosis therapy in patients with early liver cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract Background. The ammonia-monochloramine system plays an important role in Helicobacter pylori -associated gastric mucosal injury. Polaprezinc, a new antiulcer agent, has a scavenging action against monochloramine. The aim of the experiment was to investigate the inhibitory effects of polaprezinc on the H. pylori -induced gastritis in Mongolian gerbils. Materials and Methods. Mongolian gerbils fasting for 24 hours were orally given culture broth containing 2–4 × 108 colony-forming units of H. pylori ATCC 43054 per milliliter. From 4 hours after inoculation until the end of the experiment, gerbils were given chow pellets with or without 0.02% polaprezinc. All gerbils were killed 12 weeks later. The grades of H. pylori density and histologic features of gastritis were evaluated in accordance with the Updated Sydney System. The scavenging effect of polaprezinc on monochloramine was investigated spectrophotometrically. Results. Polaprezinc had little or no influence on the H. pylori density in both pyloric and fundic mucosae. However, it significantly attenuated the development of polymorphonuclear neutrophil activity, mononuclear infiltration, and surface epithelial erosion in both pyloric and fundic mucosae compared with those of the control group. H. pylori inoculation significantly increased the heights of both pyloric and fundic mucosae (mainly due to the increased height of foveolar hyperplasia), but polaprezinc inhibited the increase of mucosal thickness in both pyloric and fundic mucasae. No intestinal metaplasia was detected in this study. Spectrophotometric examination revealed that polaprezinc scavenged monochloramine. Conclusions. Polaprezinc inhibited the development of H. pylori -induced gastritis through its scavenging action against monochloramine. [ABSTRACT FROM AUTHOR]