The frequency of peripheral PD-1+ TCD4+ cells is reversely associated with serum creatinine levels in recipients of kidney allografts.

The long-term survival of solid organ allografts remains a challenge for organ transplantation systems worldwide. T-cell exhaustion has been supposed to be associated with immunologic tolerance in transplantation and might reflect the immunologic status in recipients. The aim of the present study was to compare the TCD4+ cells of kidney transplant recipients with high and low serum creatinine levels for their expressions of PD-1 and TIGIT as two well-known exhaustion markers. Blood samples were taken from 20 kidney allograft recipients with serum creatinine levels above 2 mg/dL and 20 recipients with creatinine levels below 2 mg/dL. The percentages of PD-1+ CD4+ and TIGIT+ CD4+ cells were analyzed along with the evaluation of TNF-α, IFN-γ, and IL-10 release from peripheral blood mononuclear cells (PBMCs). The patients with serum creatinine levels below 2 mg/dL demonstrated a higher frequency of PD-1+ CD4+ T-cells (p = 0.003) along with lower TNF-α secretion from PBMCs (p = 0.028). The frequency of PD-1 + CD4+ T-cells was reversely correlated with the serum creatinine levels in recipients of kidney allografts (r = 0.59, p < 0.001). Besides, the MFI of TIGIT on TCD4+ cells demonstrated a trend for higher expression in patients with serum creatinine levels below 2 mg/dL (p = 0.070). The expression of PD-1+ on CD4+ T-cells demonstrated a potential for estimation of the immunologic status of the host in interaction with alloantigens. The exhaustion markers could be regarded as potential diagnostic indicators for the evaluation of immunologic tolerance in renal transplantation.

CTLA4-Ig alleviates the allogeneic immune responses against insulin-producing cells in a murine model of cell transplantation.

The adoptive transfer of insulin-producing cells (IPCs) is one of the promising treatments for insulin-dependent diabetes mellitus. While the use of allogeneic cell resources is inevitable in the case of a series of patients, alloimmune responses are a major barrier ahead of the successful implementation of allogeneic therapeutic cells. This study is aimed at evaluating the potential of CTLA4-Ig, as an approved immunomodulatory biologic, in protecting the IPCs against allogeneic immune responses. The C57BL/6 and BALB/c mice were used to establish a murine model of allogeneic cell transplantation. The mouse bone-marrow-derived mesenchymal stem cells were in vitro differentiated into IPCs, and the in vitro as well as the in vivo immune responses against IPCs were evaluated in the presence and absence of CTLA4-Ig. The allogeneic IPCs induced the in vitro activation of CD4+ T-cells, IFN-γ release, and the proliferation of lymphocytes, which all were controlled by CTLA4-Ig. Upon in vivo transfer of IPC into an allogeneic host, the splenic CD4+ and CD8+ T-cells exhibited a significant activation, and there was a significant donor-specific antibody response. Either of the mentioned cellular and humoral responses were modulated by a CTLA4-Ig regimen. This regimen also reduced the infiltration of CD3+ T-cells into the IPC injection site along with the improved overall survival of diabetic mice. CTLA4-Ig could be a complementary therapy for improving the efficacy of allogeneic IPC therapy through modulating the cellular and humoral responses that can lead to prolonged durability of IPCs within an allogeneic host.

Urinary MicroRNAs, Possible Biomarkers for Early Detection of Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent renal disorder that causes abnormal growth of renal epithelial cells. The excessive expansion of renal epithelial cells can lead to cyst formation that is associated with serious renal complications. The early diagnosis of ADPKD makes the control of the disease somehow attainable. Regarding the diagnostic potential of microRNAs (miRs) as robust clinical biomarkers, the present study aimed to examine the potential of urinary miRs in early diagnosis of ADPKD in asymptomatic patients. METHODS: Urine samples were obtained from 20 asymptomatic ADPKD patients and 20 healthy control individuals and the miR content of the samples was extracted and converted to cDNA for the qRT-PCR experiment. The relative expressions of miR-17, miR-21, miR-143, and miR-223 were evaluated in ADPKD cases and healthy individuals. Serum levels of kidney function markers were also evaluated in the study participants. RESULTS: The urine samples of patients with ADPKD demonstrated higher levels of miR-17, miR-21, and miR-143 along with a lower miR-223 level compared to the healthy control group. CONCLUSION: This study revealed the differential expression of the studied miRs in ADPKD patients. Detection of miRs in urinary samples might provide a useful platform for early diagnosis of ADPKD in asymptomatic patients.  DOI: 10.52547/ijkd.7281.

Seroprevalence of VZV IgG antibody in kidney transplant recipients: A systematic and meta-analysis review.

BACKGROUND: Varicella-zoster virus (VZV) is a human neurotropic virus, that becomes latent in nerve ganglia. VZV infection rarely occurs after kidney transplantation but causes severe clinical features and is associated with higher mortality rates. This study was performed to survey the reports on the seroprevalence of VZV IgG antibodies in kidney transplant recipients. MATERIAL AND METHODS: Relevant studies were obtained by an online review of international databases (Web of Science, PubMed, Scopus, Science Direct, and Google scholar), and suitable studies were selected. The NOS checklist was used for the quality assessment of the selected studies. Heterogeneity assay among the primary studies was conducted by Cochran's Q test and I2 index (significance level 50%). Statistical analysis was performed using the Comprehensive Stata software (Version 14 package). RESULTS: Seroprevalence of VZV IgG in transplant recipients has been reported in ten studies. After combining the results of preliminary studies using a random effect model, the overall estimate of IgG positivity to VZV in transplant recipients was obtained equal to 98%. CONCLUSION: In this study, our results demonstrated that VZV is a prevalent infectious agent in kidney transplant recipients. A prophylactic vaccine may provide an effective strategy for preventing VZV in renal transplant recipients and also provide prophylaxis against the occurrence of post-herpetic neuralgia in immunocompetent patients.

The immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy individuals: A systematic review and meta-analysis.

OBJECTIVE: Inactivated (killed) vaccines against COVID-19 have been widely used for the control of the pandemic condition. We performed a systematic and meta-analysis review of randomized, double-blind, placebo-controlled trials of the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. METHODS: In the present study, all research and evidence were extracted from the available online databases. Two researchers randomly evaluated the assessment of the research sensitivity. Finally, after quality assessment and regarding the specific inclusion and exclusion criteria, the eligible articles were entered for meta-analysis. The heterogeneity between the results of the studies was measured using test statistics (Cochran's Q) and the I2 index. The forest plots illustrated the point and pooled estimates with 95% confidence intervals (crossed lines). All statistical analyses were performed using Comprehensive meta-Analysis V.2 software. RESULTS: This meta-analysis included six primary studies investigating the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. According to the pooled prevalence (95% confidence interval), neutralizing antibody responses 28 days after receiving the second dose regarding different ages and micrograms per dose was 95.50% (CI: 93.2-97.1%). Our results showed that antibody levels were higher in the 6 µg group than in other groups. 98.3% (CI: 94.2-99.5%). CONCLUSION: Since the rapid development of vaccinations has sparked widespread public anxiety regarding vaccine efficacy. Governments and unvaccinated individuals, particularly those with vaccination reluctance, will be interested in and benefit from the findings of this systematic study.

New insights on the monitoring of solid-organ allografts based on immune cell signatures.

Attaining a fair long-term allograft survival remains a challenge for allogeneic transplantation worldwide. Although the emergence of immunosuppressants has caused noticeable progress in the management of immunologic rejection, proper application of these therapeutics and dose adjustments require delicate and real-time monitoring of recipients. Nevertheless, the majority of conventional allograft monitoring approaches are based on organ damage or functional tests that render them unable to predict the rejection events in early time points before the establishment of a functional alloimmune response. On the other hand, biopsy-based methods include invasive practices and are accompanied by serious complications. In recent years, there have been a myriad of attempts on the discovery of reliable and non-invasive approaches for the monitoring of allografts that regarding a close relationship between allografts and hosts' immune system, most of the attempts have been devoted to the studies on the immune response-associated biomarkers. The discovery of gene and protein expression patterns in immune cells along with their phenotypic characterization and secretome analysis as well as tracking the immune responses in allograft tissues and clinical specimens are among the notable attempts taken to discover the non-invasive predictive markers with a proper coincidence to the pathologic condition. Collectively, these studies suggest a list of candidate biomarkers with ideal potentials for early and non-invasive prediction of allograft rejection and shed light on the way towards developing more standardized and reproducible approaches for monitoring the allograft rejection.

Blockade of TGF-ßR improves the efficacy of doxorubicin by modulating the tumor cell motility and affecting the immune cells in a melanoma model.

TGF-ß contributes to drug resistance and the invasiveness of tumor cells and weakens the anti-tumor immune responses. The present study aimed at examining the efficacy of the combination of SB431542, as a specific inhibitor of TGF-ßR, and doxorubicin in controlling the melanoma tumor in mice. The impact of the combination of the doxorubicin and SB431542 on the cell growth, apoptosis, migration, and invasiveness of B16-F10 cells was examined. Besides, the B16-F10 tumor was induced in C57BL/6 mice, and the effects of the mentioned treatment on the tumor volume, survival, and the exhaustion state of T cells were evaluated. Although the combination of doxorubicin and SB431542 did not exhibit synergism in the inhibition of cell growth and apoptosis induction, it efficiently prohibited the migration and the epithelial to mesenchymal transition of B16-F10 cells, and the combination of doxorubicin and SB431542 caused an increase in mRNA levels of E-cadherin and, on the other hand, led to a decline in the expression of Vimentin. Tumor volume and the survival of tumor-bearing mice were efficiently controlled by the combination therapy. This treatment also eventuated in a decrease in the percentage of PD-L1+, TCD4+, and TCD8+ cells as indicators of exhausted T cells within the spleens of tumor-bearing mice. Blockade of TGF-ßR also propelled the RAW 264.7 cells towards an anti-tumor M1 macrophage phenotype. The inhibition of TGF-ßR demonstrated a potential to increase the efficacy of doxorubicin chemotherapy by the means of affecting cellular motility and restoring the anti-tumor immune responses.

Zoledronic acid-loaded lipidic nanoparticles enhance apoptosis and attenuate invasiveness by inhibiting epithelial to mesenchymal transition (EMT) in HepG2 cancer cells.

The aim of this study was to evaluate the potential of zoledronic acid (ZOL)-loaded lipidic nanoparticles (ZOL-NLCs) in enhancing the efficiency of paclitaxel (Pac) in the context of cytotoxicity, apoptosis, and invasiveness of HepG2 hepatocellular carcinoma cells. ZOL-NLCs were characterized in terms of zeta potential, particle size, and scanning electron microscope (SEM) as well as cell internalization. To measure the anti-proliferative effects of ZOL-NLCs, annexin-V/PI and MTT assays were employed. Real-time PCR and western blot analysis were performed to identify the molecular mechanisms underlying the apoptosis in response to the studied conditions. Furthermore, the transwell migration assay was applied to clarify the role of applied formulations on the invasiveness of HepG2 cells. Our results demonstrated that the optimized ZOL had an average particle size of 105 ± 6 nm with a nearly narrow size distribution. The IC50 values for ZOL and ZOL-NLCs were 90 ± 3.1 and 54.6 ± 2.4 µM, respectively. The population of apoptotic cells was increased from 17 ± 2% to 27 ± 4% (p < 0.05) in response to treatment with ZOL-NLCs. ZOL-loaded nanoparticles triggered the mRNA expression of Bax as pro-apoptotic marker and E-cadherin as epithelial one along with a decrease in mesenchymal marker, N-cadherin, and Bcl-xl as an anti-apoptotic marker in HepG2 cells. These outcomes were consistent with western blot analysis of protein expressions. Besides, ZOL-incorporated lipidic nanoparticles reduced the migration of HepG2 cells significantly. Our data suggest that the formulation of ZOL into lipidic nanoparticles can be considered a potential therapeutic approach that can enhance the efficacy of Pac chemotherapy.

Dialysis-Induced Immune Dysregulations and Their Possible Impacts on COVID-19.

Hemodialysis (HD) patients display metabolic and immunologic alterations that renders their immune responses to be dysregulated. These patients generally have problems in mounting effective immune responses against pathogens such as viruses. On the other hand they typically have higher levels of inflammatory cytokines in their peripheral blood. Both of these features may work in favor of COVID-19. Since robust immune responses are needed to prevent infection in the initial stages of COVID-19, the impaired immune system may not be able to cope effectively with the highly replicating SARS-CoV2. In advanced stages of the disease wherein the inflammation as well as the cytokine storm are the core players, a high baseline inflammatory cytokines could intensify and substantially exacerbate the immunopathological situation. Presence of COVID-19 in HD patients may also be a complex immunological condition. Immunological alterations in HD patients and their potential effects on the fate of the SARSCoV- 2 infection are discussed here. Case reports describing the occurrence of COVID-19 in HD patients have also been reviewed in this study.

PD-L1 overexpression conveys tolerance of mesenchymal stem cell-derived cardiomyocyte-like cells in an allogeneic mouse model.

Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4+ and CD8+ T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8+ T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4+ and CD8+ T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction.

Current status of COVID-19 among hemodialysis patients in the East Azerbaijan Province of Iran.

INTRODUCTION: Management of vulnerable patients during the COVID-19 pandemic requires careful precautions. Hemodialysis patients constitute a large group of at-risk patients that not only suffer from a compromised immune system but also are at a higher risk due to frequent admission to healthcare units. Therefore, a better understanding on the pathogenesis and possible risk factors of COVID-19 in hemodialysis patients is of high importance. METHODS: A total of 670 maintained hemodialysis patients from all dialysis units of the East Azerbaijan Province of Iran, including 44 COVID-19 patients were included in the present study. Possible associations between the backgrounds of patients and the incidence of COVID-19 were assessed. Also, hemodialysis patients with COVID-19 were compared to 211 nonhemodialysis COVID-19 patients. FINDINGS: Chronic glomerulonephritis patients and those with blood group A demonstrated a higher incidence of COVID-19. On the other hand, patients with blood group AB+ and those with hypertension etiology of kidney failure demonstrated a lower incidence of COVID-19. Hemodialysis patients with COVID-19 had higher counts of polymorphonuclears (PMNs) in their peripheral blood compared to other COVID-19 patients. DISCUSSION: A better comprehension on the risk factors associated with COVID-19 in hemodialysis patients can improve our understanding on the pathogenesis of COVID-19 in different situations and help the enhancement of current therapeutics for COVID-19 in hemodialysis patients.

Mouse bone marrow-derived mesenchymal stem cells acquire immunogenicity concurrent with differentiation to insulin-producing cells.

BACKGROUND: Although mesenchymal stem cells (MSCs) are regarded as immune-elusive and even immunosuppressive, recent evidence suggests that allogeneic immune response might is inevitable in the case of some lineages differentiated from MSCs. Regarding the importance of allogeneic IPCs and MSCs in pre-clinical and clinical studies, the present study aimed to investigate the possible changes in the immunogenicity of MSCs during the differentiation to IPCs in a murine model of allogeneic transplantation. MATERIAL AND METHODS: Two mouse strains, C57BL/6 (H2Db) and BALB/c (H2Dd) were selected to establish an allogeneic cell transplantation model. Bone marrow MSCs were differentiated into IPCs and the expression of H2D, CD80, and Qa-2 molecules were evaluated via flowcytometry on MSCs and IPCs. The differentiated and undifferentiated MSCs were encountered to allogeneic splenocytes and the proliferation, CD44 activation marker, and cytokine release in the splenocytes were evaluated. RESULTS: IPCs exhibited increased expression of MHC-I and CD80 that elicited an allogenic response including the activation-induced proliferation of splenocytes, activation of CD4+ T cells, and IFNγ response. CONCLUSIONS: MSCs acquire immunogenicity after differentiation to functional IPCs, which might cause decreased efficacy in the case of allogeneic transplantation. Careful precautions might be critical for saving the IPCs against the detrimental allogeneic responses.

Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line.

The potential role of microRNAs (miRNA or MIR) as therapeutic molecules has moved them from basic research to the field of cancer therapy. High expression of miR-93 and low expression of miR-34a have previously been indicated in prostate cancer (PC), which is the second leading cause of cancer-related death in men. Androgen receptor (AR) and prostate-specific antigen (PSA) play key roles in the initiation and progression of this cancer. Therefore, this study aimed to investigate the effects of the transfection and co-transfection of miR-34a mimic and miR-93 inhibitor with or without epigallocatechin-3-gallate (EGCG) on prostate cancer cell line and also to evaluate their effects on the expression of AR, PSA. Human lymph node carcinoma of the prostate (LNCaP) cells were treated with miR-34a mimic or/and miR-93 inhibitor with or without EGCG. Gene or protein expressions were assessed by real-time PCR or western blotting of lysates. The transfection with miR-34a mimics significantly reduced the mRNA expression of AR (p=0.0016), and PSA (p=0.038) compared to the control. Also, the miR-93 inhibitor led to a decrease in the mRNA expression of AR (p=0.0057) and PSA (p>0.05) compared to the control group. Furthermore, the co-transfection, along with EGCG, caused more decrease in both the AR (p<0.001) and the PSA (p=0.003) expression compared with the co-transfection without EGCG. Our study indicates that the reduced expression of AR and PSA in PC cells followed by treatment with miR-34a mimic and miR-93 inhibitor and their combination with EGCG as a natural substance may be a promising therapeutic way for controlling the growth of these malignant cells.

An update on potentials and promises of T cell co-signaling molecules in transplantation.

The promising outcomes of immune-checkpoint based immunotherapies in cancer have provided a proportional perspective ahead of exploiting similar approaches in allotransplantation. Belatacept (CTLA-4-Ig) is an example of costimulation blockers successfully exploited in renal transplantation. Due to the wide range of regulatory molecules characterized in the past decades, some of these molecules might be candidates as immunomodulators in the case of tolerance induction in transplantation. Although there are numerous attempts on the apprehension of the effects of co-signaling molecules on immune response, the necessity for a better understanding is evident. By increasing the knowledge on the biology of co-signaling pathways, some pitfalls are recognized and improved approaches are proposed. The blockage of CD80/CD28 axis is an instance of evolution toward more efficacy. It is now evident that anti-CD28 antibodies are more effective than CD80 blockers in animal models of transplantation. Other co-signaling axes such as PD-1/PD-L1, CD40/CD154, 2B4/CD48, and others discussed in the present review are examples of critical immunomodulatory molecules in allogeneic transplantation. We review here the outcomes of recent experiences with co-signaling molecules in preclinical studies of solid organ transplantation.

Human charcoal-stripped serum supplementation enhances both the stearoyl-coenzyme a desaturase 1 activity of cumulus cells and the in vitro maturation of oocytes.

Obtaining a better outcome in assisted reproductive technology remains to be attained. In the case of in vitro fertilization (IVF), oocyte maturity is paramount for achieving a successful pregnancy. Maternal serum supplementation of in vitro maturation (IVM) medium can increase the rate of oocyte IVM. The aim of the present study was to compare the effect of whole and charcoal-stripped serum supplementation on IVM and the activity index of stearoyl-coenzyme A desaturase 1 (SCD1) in cumulus cells enclosing the oocyte as a molecular indicator of oocyte quality. Cumulus cells and germinal vesicle immature oocytes were collected from 76 women with polycystic ovarian syndrome during an IVF cycle. Serum samples were pooled from healthy women and were applied as whole or charcoal-stripped serum supplements. SCD1 expression and activity were measured by quantitative polymerase chain reaction (PCR) and gas-liquid chromatography, respectively. Charcoal-stripped serum at an amount of 10% showed a higher potency in increasing the SCD1 expression and activity index than whole serum (>1.5 fold, p < 0.001). An increase in the IVM rate was also observed in oocytes cultured in the presence of 10% charcoal-stripped serum compared to the control group (1.9 fold, p = 0.031). Therefore, charcoal-based lipid depletion as a simple and preparative strategy may increase the beneficial effect of serum supplementation in oocyte IVM culture.

SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells.

Stromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells. Especially they play a key role in tumor immune surveillance. Whereas it was not well understood whether SDF-1α modulates anti-tumor immune response or not, the purpose of the present study was to investigate the effect of SDF-1α on the cytotoxic properties of peripheral blood NK cells. Human peripheral blood NK cells were freshly isolated using MACSxpess system and cultured in the presence or absence of recombinant human SDF-1α or SDF-1α plus CXCR4 antagonist, AMD3100. CD107a degranulation assay was conducted through the co-culture of NK cells with K562 cells. The percentage of CD107a positive cells was assessed by flowcytometry. Effect of SDF-1α was also examined on the mRNA levels of NKG2A and NKG2D as indicator examples of NK cell inhibitory and activating receptors, respectively. SDF-1α significantly decreased the degranulation activity of NK cells (p=0.04). The mRNA content of NKG2D was down-regulated under the influence of SDF-1α (p=0.03). Moreover, AMD3100 exhibited a trend in recovering the NKG2D mRNA level to its un-treated state (p=0.05).  The present study reveals that SDF-1α has a negative impact on NK cell activity and might is involved in tumor immune-suppression. Thus, it can be concluded that microenvironment manipulations targeting SDF-1α may reinforce current cancer therapies by disturbing one of the immune-suppressive axes in the cancerous milieu.

Steroid-depleted polycystic ovarian syndrome serum promotes in vitro oocyte maturation and embryo development.

In vitro maturation (IVM) of immature oocytes obtained from patients with polycystic ovarian syndrome (PCOS) is considered as a novel strategy in order to reduce clinical side effects and cost of in vitro fertilization (IVF) technique. The aim of this study was to evaluate the effects of PCOS whole and steroid-depleted serums on in vitro oocyte maturation indices. Patients with PCOS were selected according to the Rotterdam criteria. Cumulus-oocyte complexes and blood serums were collected and pooled. Cumulus cells and immature oocytes were treated with 10% whole or steroid-depleted serums. Stearoyl-CoA desaturase-1 (SCD1) and cyclooxygenase-2 (COX2) expression levels in cumulus cells were evaluated by quantitative PCR. Fatty acid composition of cumulus cells was analyzed using gas-liquid chromatography. Polar body observation was considered as the oocyte maturation index. Oleate (1.28-fold, p = .006), SCD1 expression (450-fold, p = .001), and COX2 expression (35-fold, p = .02) in cumulus cell, as well as oocyte maturation (p < .001) and in vitro embryo development (p < .05) were significantly higher in treatment with steroid-depleted serum compared to that of whole serum. Steroid depletion of PCOS serum improved its capacity to increase success rate of oocyte maturation, intra-cytoplasmic sperm injection and early embryo development.

Effects of a triplex mixture of Peganum harmala, Rhus coriaria, and Urtica dioica aqueous extracts on metabolic and histological parameters in diabetic rats.

CONTEXT: Several therapeutic effects such as antioxidant and blood glucose-lowering activities have been reported for Peganum harmala L (Zygophyllaceae) (PH) seeds, Rhus coriaria L (Anacardiaceae) (RC) fruits, and Urtica dioica L (Urticaceae) (UD) leaves. OBJECTIVE: This study investigates the effects of a triplex mixture (1:1:1) of these medicinal plants on metabolic and histological parameters in diabetic rats. MATERIALS AND METHODS: Aqueous extracts of PH, RC and UD were administered as either monotherapy or in combination at a final dose of 200 mg/kg to alloxan-induced diabetic rats by daily gavage. Biochemical parameters including blood glucose, liver function-related enzymes, lipid profile, and creatinine were estimated by spectrophotometric methods. Tissues from the liver and kidney stained with hematoxylin/eosin were histologically examined. The results obtained from the exposure groups were compared to either healthy or diabetic control groups. RESULTS: Compared with the diabetic control rats, all aqueous extracts (ED50 = 11.5 ± 2.57 mg/ml) led to significant decreases in the levels of ALP (1.39-2.23-fold, p < 0.05), low-density lipoprotein cholesterol (LDL-C) (1.79-3.26-fold, p < 0.05), and blood glucose (1.27-4.16-fold, p < 0.05). The serum concentrations of TG was decreased only by treatment with UD and triplex mixture (1.25- and 1.20-fold, respectively, p < 0.05). Among the studied parameters, alanine aminotransferase (ALT), LDL-C, TG, and creatinine recovered to healthy control levels after 4 weeks of treatment with the extract mixture. CONCLUSION: This study showed that PH, RC, and UD extracts, especially their combination, had significant antidiabetic, hypolipidemic, and liver and renal damage recovering effects.