Determination of the median lethal dose of zinc gluconate in mice and safety evaluation.

BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.

Preliminary Comparison of Fractional Absorption of Zinc Sulphate, Zinc Gluconate, and Zinc Aspartate after Oral Supple-Mentation in Healthy Human Volunteers.

(1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers with three different Zn complexes acquired with milk. (2) Methods: The design was a double-blind, three-period crossover trial. The volunteers were randomly divided into three groups. Each individual consumed 200 mL of bovine milk and rotated through a simultaneous administration of a single oral dose of 70ZnSO4, 70Zn-Gluconate (70Zn-Glu), and 70Zn-Aspartate (70Zn-Asp), equivalent to 2.0 mg 70Zn, followed by 2 weeks of wash-out. An estimation of the FZA for comparative purposes was computed by the isotopic ratio between 66Zn and 70Zn in urine collected before and 48 h after administration. (3) Results: The estimated FZA was found to be significantly higher for 70Zn-Asp when compared to the other forms, while the FZA of 70Zn-Glu was found to be significantly higher than 70ZnSO4. (4) Conclusions: The results of this study suggest that complexing Zn with aspartate in milk could be a useful tool to improve FZA in individuals at risk of Zn deficiency. These results provide a rationale for conducting further studies on Zn-Asp preparations.

Attenuated effect of zinc gluconate on oxidative stress, inflammation, and angiogenic imbalance in pre-eclampsia rats.

AIMS: Pre-eclampsia (PE) is a common obstetric disease associated with oxidative stress, systemic inflammation, and angiogenic imbalance, whereas zinc (Zn) presents anti-oxidative and anti-inflammatory effects. This study is to investigate whether zinc gluconate (ZG) supplementation may ameliorate the early signs, adverse pregnancy outcomes, and pathogenic processes of PE in an animal model. MAIN METHODS: Forty pregnant Wistar rats were randomly divided into four groups: blank control (treated with normal saline, NS), Zn control (treated with ZG and followed by NS), PE model (treated with NS and followed by nitro-L-arginine methyl ester, L-NAME), and PE intervention (treated with ZG and followed by L-NAME). ZG (5 mg/kg/day) or NS was administered by gavage from day 0 to 19 of gestation, and L-NAME (80 mg/kg/day) or NS was subcutaneously injected from day 4 to 19 of gestation. The blood pressure, urinary protein, and pregnancy outcomes were recorded. Oxidative stress, inflammation, and angiogenic homeostasis were evaluated. KEY FINDINGS: PE rats exhibited oxidative stress (reduced SOD, CAT, and GSH, and increased MDA and 3-NT), inflammation (increased IL-6 and TNF-α), and angiogenic imbalance (reduced VEGF and PlGF, and increased sFlt-1). After intervention with ZG, the blood pressure and urinary protein levels were reverted, and the pregnancy outcomes were improved. The oxidative stress, inflammation, and angiogenic imbalance were effectively restored in accompany by increased Zn and MT levels. SIGNIFICANCE: ZG can ameliorate the early signs and pathological processes of PE in the animal model, indicating the value of zinc supplementation during pregnancy for PE prevention.

Inhibition of SARS-CoV-2 replication by zinc gluconate in combination with hinokitiol.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is currently the major challenge to global public health. Two proteases, papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro or Mpro), are indispensable for SARS-CoV-2 replication, making them attractive targets for antiviral therapy development. Here we screened a panel of essential metal ions using a proteolytic assay and identified that zinc gluconate, a widely-used zinc supplement, strongly inhibited the proteolytic activities of the two proteases in vitro. Biochemical and crystallographic data reveal that zinc gluconate exhibited the inhibitory function via binding to the protease catalytic site residues. We further show that treatment of zinc gluconate in combination with a small molecule ionophore hinokitiol, could lead to elevated intracellular Zn2+ level and thereby significantly impaired the two protease activities in cellulo. Particularly, this approach could also be applied to rescue SARS-CoV-2 infected mammalian cells, indicative of potential application to combat coronavirus infections. Our studies provide the direct experimental evidence that elevated intracellular zinc concentration directly inhibits SARS-CoV-2 replication and suggest the potential benefits to use the zinc supplements for coronavirus disease 2019 (COVID-19) treatment.

Chitosan-poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor benefit for antibacterial and wound healing.

Chitosan/poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor (ZnG/rhEGF@Chit/Polo) were developed as a convenient, safe and effective dressing for skin wound treatment. Their fabrication procedure and characterization were reported, and their morphology was examined by a scanning electron microscope. Antibacterial and biofilms activities were evaluated by in vitro tests to reveal the inhibitory effects and scavenging activity on the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. ZnG/rhEGF@Chit/Polo was also investigated as a potential therapeutic agent for wound healing therapy. In vivo wound healing studies on rats for 21 days proves that ZnG/rhEGF@Chit/Polo supplements the requisite Zn2+ and rhEGF for wound healing to promote the vascular remodeling and collagen deposition, facilitate fibrogenesis, and reduce the level of interleukin 6 for wound basement repair, and thus is a good wound therapy.

A new therapeutic horizon in diaper dermatitis: Novel agents with novel action.

OBJECTIVE: This review looks at novel combinations of topical agents (i.e., zinc gluconate, zinc oxide, dexpanthenol, and taurine) that target a combination of mechanisms in diaper dermatitis. METHODS: A literature search of published studies was conducted using the search terms "diaper dermatitis", "treatment of diaper dermatitis in infants", "treatment of diaper dermatitis in adults", "nonsteroidal", "nonantibiotic", "antiinflammatory", "moisturizer", and "treatment for irritation". A total of 207 related articles were screened, and those categorized as clinical trials and reviews were studied and compared. Articles with common themes were categorized, summarized, and presented herein. RESULTS: Diaper dermatitis, also referred to as diaper rash, napkin dermatitis, and nappy rash, is the most common skin eruption in infants and toddlers. In the last several years, there have been several technologic advances in diaper design to lessen the severity of diaper dermatitis symptoms. However, due to the unique environment of the diaper area, children and adults continue to have recurring symptoms of diaper dermatitis. Both commercially available products and certain home remedies are considered effective for managing sensitive and delicate skin in the diaper area. These topical agents create a protective barrier over the skin and reduce the impact of external irritants, which cause the reddening and burning sensation often associated with diaper dermatitis. CONCLUSION: A range of therapeutic strategies for preventing and controlling diaper dermatitis are summarized in this manuscript.

Zinc Gluconate-Loaded Chitosan Nanoparticles Reduce Severity of Collagen-Induced Arthritis in Wistar Rats.

Rheumatoid arthritis (RA) is the most prevalent autoimmune disease affecting about 1% world population. Zinc (Zn) is necessary for the maintenance of bone homeostasis and the level of Zn was reported to be decreased in RA patients and collagen-induced arthritic rats. Effective delivery of Zn has been reported using zinc gluconate but oral absorption of Zn from zinc gluconate (ZG) is very low in humans. Zn supplementation reduces disease severity in patients suffering from chronic, refractory RA and exerts mild and transient side effects. The aim of this study was to synthesize and characterize zinc gluconate-loaded chitosan nanoparticles (ZG-Chit NPs) and to evaluate and compare therapeutic efficacy of ZG-Chit NPs and zinc gluconate against collagen-induced RA in Wistar rats. The nanoparticles were formulated by ionic gelation method and the hydrodynamic diameter was 106.5 ± 79.55 nm as measured using DLS. The particle size, shape, and surface morphology was further confirmed by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. These nanoparticles showed good cytocompatibility against foreskin fibroblasts (BJ) and L929 cells. Arthritic rats were treated with ZG (20 mg/kg body weight, intraperitoneally) and equivalent doses of ZG-Chit NPs. The treatment of both ZG and ZG-Chit NPs reduced the severity of arthritis as evidenced by reduced joint swelling, erythema, and edema but ZG-Chit NPs exhibited superior efficacy. Furthermore, it was found that ZG and ZG-Chit NPs attenuate biomarkers of inflammation (C-reactive protein, myeloperoxidase, nitric oxide, TNF-α, and IL-1ß) and oxidative stress (articular elastase, lipid peroxidation, catalase, glutathione, and superoxide dismutase). The results of the histopathology further confirmed that ZG-Chit NPs markedly suppressed infiltration of inflammatory cells as compared to ZG at the ankle joint tissue. Immunohistochemical analysis also revealed that treatment with ZG-Chit NPs resulted in reduced pro-inflammatory marker (TNF-α, IL-6, and iNOS) expression and enhanced SOD1 expression. Overall, this study suggests that ZG and ZG-Chit NPs suppressed the severity of arthritis plausibly mediated by attenuation of inflammation and oxidative stress and more importantly ZG-Chit NPs exhibited superior efficacy as compared to ZG.

Clinical effect of zinc gluconate combined with tetralogy of viable bifidobacterium tablets in the treatment of infantile autumn diarrhea / 中国基层医药

Objective To study the clinical effect of zinc gluconate combined with tetralogy of viable bifidobacterium tablets in the treatment of infantile autumn diarrhea .Methods 76 children with diarrhea in Lishui Hospital of Traditional Chinese Medicine from September to November in 2014 and from September to November in 2015 were selected as research subjects .All patients were randomly divided into control group ( n=38 ) and observa-tion group(n=38) by registration order.The control group was given tetralogy of viable bifidobacterium tablets ,while the observation group was given zinc gluconate combined with tetralogy of viable bifidobacterium tablets .The disappea-ring time of disease and the clinical symptoms after treatment for 72 h were compared between the two groups . Results The disappearing time of fever in the observation groupwas (28.81 ±5.72) h,which in the control group was (41.67 ±7.91)h,the difference was statistically significant between the two groups (t=10.358,P=0.011).The disappearing time of abdominal distension in the observation group was (40.28 ±7.96)h,which in the control group was (52.35 ±11.54)h,the difference was statistically significant between the two groups (t=7.334,P=0.021).The disappearing time of emesis in the observation groupwas (35.71 ±10.37)h,which in the control group was (50.66 ± 12.89)h,the difference was statistically significant between the two groups (t=9.214,P=0.017).The total effective rate of the observation group was 97.37％,which was higher than 81.58％ of the control group (χ2 =15.240,P<0.05 ) .In addition ,no complication was observed during the treatment .Conclusion The combination therapy of zinc gluconate and tetralogy of viable bifidobacterium tablets for infantile autumn diarrhea has high efficacy ,less adverse reaction,short therapy time ,and it has clinical value .

Effect of zinc gluconate, sage oil on inflammatory patterns and hyperglycemia in zinc deficient diabetic rats.

BACKGROUND: The relationship between zinc homeostasis and pancreatic function had been established. In this study we aimed firstly to configure the inflammatory pattern and hyperglycemia in zinc deficient diabetic rats. Secondly to illustrate the effect of two selected agents namely Zinc gluconate and sage oil (Salvia Officinalis, family Lamiaceae). METHODS: Rats were fed on Zinc deficient diet, deionized water for 28days along with Zinc level check up at intervals to achieve zinc deficient state then rats were rendered diabetic through receiving one dose of alloxan monohydrate (120mg/kg) body weight, classified later into 5 subgroups. RESULTS: Treatment with sage oil (0.042mg/kg IP) and Zinc gluconate orally (150mg/kg) body weight daily for 8 weeks significantly reduced serum glucose, C-reactive protein (CRP), Tumor necrosis factor alpha (TNF- α), interleukins-6 1 ß, inflammatory8 (IFN È£), pancreatic 1L1-ß along with an increase in serum Zinc and pancreatic Zinc transporter 8 (ZNT8). Histopathological results of pancreatic tissues showed a good correlation with the biochemical findings. CONCLUSIONS: Both sage oil and zinc gluconate induced an improvement in the glycemic and inflammatory states. This may be of value like the therapeutic agent for diabetes.

Role of oral zinc supplementation for reduction of neonatal hyperbilirubinemia: a systematic review of current evidence.

BACKGROUND: Neonatal hyperbilirubinemia is frequently seen condition in the NICU. Oral zinc has been tried for the prevention of hyperbilirubinemia. AIMS: To evaluate the role of oral zinc supplementation for reduction of neonatal hyperbilirubinemia in term and preterm infants. METHOD: The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other data base. RESULTS: This review included six RCT that fulfilled inclusion criteria. One study evaluated the role of zinc in very low birth weight (VLBW) infants and remaining enrolled neonates ≥35 weeks of gestation. The dose of zinc varied from 5 to 20 mg/day and duration from 5-7 days. All the studies used zinc sulfate, only one study used zinc gluconate. The total neonates enrolled in these different RCT are 749. CONCLUSION: Role of zinc in the prevention of neonatal hyperbilirubinemia is not supported by the current evidence. Only one study was able to show reduction in the mean TSB level and requirement of phototherapy with zinc, and the remaining studies did not report any positive effect. None of the studies showed any effect on the duration of phototherapy, incidence of phototherapy, age of starting of phototherapy and any serious adverse effect.

The Effect of Zinc and Selenium Supplementation Mode on Their Bioavailability in the Rat Prostate. Should Administration Be Joint or Separate?

It is thought that zinc and selenium deficiency may play a significant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was significantly elevated already after the first month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate significantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the first time that these elements should not be administered jointly in supplementation.

Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora.

Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200µM ZG for 0-24h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1ß protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons.

Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 µg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 µg serum Zn/dL failed to increase their serum zinc to ≥70 µg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.

Effects of surgical and chemical sterilization on the behavior of free-roaming male dogs in Puerto Natales, Chile.

Population management of free-roaming domestic dogs (Canis lupus familiaris) is of interest due to the threat these animals pose to people, other animals and the environment. Current sterilization procedures for male dogs include surgical and chemical methods. However, little is known about how these procedures affect their behavior. The primary objective of this study was to investigate changes in selected behaviors following chemical and surgical sterilization in a male free-roaming dog (FRD) population in southern Chile. We also examined the association between serum testosterone levels and behaviors thought to be influenced by circulating androgens. A total of 174 dogs were randomly assigned to either a surgical or chemical sterilization group, or a control group. At the onset of the intervention period, 119 dogs remained and 102 dogs successfully completed the study. Each dog was monitored pre- and post-intervention using video recordings, GPS collars, and blood samples for the measurement of testosterone. Analysis of behavior revealed that surgically castrated dogs showed no reduction of sexual activity or aggression when compared to their pre-intervention behavior. Chemically sterilized dogs showed a statistically significant increase in dog-directed aggression, but no change in sexual activity. There was no change in home range size in any groups between the pre- and post-intervention measurement. We found no consistent association between levels of serum testosterone concentration and behavioral changes in any of the groups. This study presents the first detailed behavioral observations following surgical and chemical sterilization in male FRDs. The information generated is highly relevant to communities struggling with the control of FRDs. Complementary studies to further our understanding of the effects of male sterilization on the behavioral and reproductive dynamics of FRD populations are needed.

Effect of pidotimod,zinc gluconate,bifico on immune function in the treatment of infants with persistent / 中国基层医药

Objective To observe the effect of pidotimod,zinc gluconate,bifico on immune function in the treatment of infants with persistent chronic diarrhea,and to provide new options for clinical treatment.Methods The infants with persistent chronic diarrhea were selected as study objects,all patients were randomly divided into 40 patients of the observation group and 40 patients of control group,both group were given conventional treatment, which including ORS oral rehydration,vitamin supplements,electrolytes,correct acid -base balance,smecta.The con-trol group were given zinc gluconate and bifico(Bifico 20mg/kg,tid;oral zinc gluconate,10 -20mg/d (zinc compu-ting),tid),the observation group were given pidotimod(400mg/times,qd)on the basis of the control group.Both group had been treated for three weeks and been followed for 12month.The symptoms improvement was observed be-fore and after treatment,the time of stool frequency normalization and stool Characters normalization were recorded,the blood were extracted for detecting immunoglobulin (IgA,IgG)and T lymphocyte subsets (CD +3 ,CD +4 ,CD +8 ),the effect and Diarrhea relapses of follow -up of 6 months were evaluated.Results The time of stool frequency normali-zation and stool characters normalization in the observation group and the control group were (4.5 ±1.5 )d and (7.8 ±2.2)d,(4.3 ±1.6)d and(7.5 ±2.0)d,the observation group were significantly shorter than the control group,t =7.146,8.108,all P <0.01.The number of diarrhea relapses of follow -up of 6 months in observation group and the control group were (2.05 ±1.62)times and (3.73 ±1.65 )times,(3.38 ±2.12)times and (5.15 ± 2.32)times,the observaiton group were significantly less than the control group,t =3.845,3.636,all P <0.05.The IgA,IgG,CD +3 ,CD +4 ,of observation group and control group after treatment were (1.75 ±0.10)g/L vs.(1.50 ± 0.11)g/L,(8.95 ±1.42)g/L vs.(8.02 ±1.25)g/L,(57.5 ±6.6)% vs.(50.5 ±6.0)%,(39.5 ±3.5)% vs. (35.6 ±3.6)%,the observation group were significantly higher than before treatment (t =3.633,5.835,9.534, 6.427 and 3.274,3.643,4.732,3.658,all P <0.05).The IgA,IgG,CD +3 ,CD +4 of observation group after treatment was significantly higher than the control group (t =3.553,3.434,3.568,3.336,all P <0.05).The total effective rate of observation group was 90.0%,the control group was 72.5%,the difference was statistically significant(χ2 =6.664,P <0.05).Conclusion The method containing pidotimod,zinc gluconate and bifico can adjust the immune dysfunction,improve immune and humoral immunity,prevent secondary infection,improve nutrition,promote mucosal tissue repair,improve treatment efficacy and reduce the long -term recurrence,worthy of clinical use in the treatment of infants with persistent chronic diarrhea.

The influence of selected antihypertensive drugs on zinc, copper, and iron status in spontaneously hypertensive rats.

Mineral homeostasis in hypertensive patients may be affected by hypotensive drugs. The aim of this study was to assess the influence of selected antihypertensive drugs on mineral homeostasis in a rat model of hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) were treated with perindopril, metoprolol, indapamide, amlodipine, or no drug for 45 days. In another experiment, the SHRs were treated with indapamide or amlodipine in the presence of zinc and copper gluconate supplement. Lipids, glucose, and insulin levels along with superoxide dismutase and catalase activities were assayed in serum. Iron, zinc, and copper concentrations in serum, erythrocytes, and tissues were determined using the flame atomic absorption spectrometry. Blood pressure was measured using a tail-cuff plethysmograph. Treatment with indapamide and amlodipine was found to significantly lower zinc levels in serum, erythrocytes, livers, and spleens of the SHRs, as well as copper levels in the kidneys, compared with the control no-drug group. A markedly higher concentration of glucose was found in the indapamide-treated rats. Supplementing the indapamide-treated SHRs with zinc and copper gluconate resulted in a significant decrease in both systolic and diastolic blood pressure, and also lowered serum glucose and triglyceride concentrations and HOMA (homeostasis model assessment-insulin resistance) values. The results show that indapamide and amlodipine disturb zinc and copper homeostasis in SHRs. Supplementation with zinc and copper restores mineral homeostasis in SHRs treated with indapamide and amlodipine, and also corrects metabolic imbalances while improving the antihypertensive efficiency of indapamide.