Computational and in vitro analyses on synergistic effects of paclitaxel and thymoquinone in suppressing invasive breast cancer cells.

BACKGROUND: In the present experiment, we evaluated the impact of thymoquinone (TQ) and paclitaxel (PTX) treatment on MDA-MB-231 cell line growth inhibition via controlling apoptosis/autophagy. MATERIALS AND RESULTS: MDA-MB-231cells were exposed to PTX (0, 25, 50, 75, and 100 nM), TQ (0, 25, 50, 75, and 100 µM), and combinations for 48 h. After the MTT assessment, dose-response curves and IC50 values were calculated, and the combination synergism was evaluated using the Compusyn software. Following the treatment with PTX, TQ, and combinations at IC50 doses, the expression of apoptosis and autophagy genes was assessed in cells. The GraphPad Prism program was used to analyze the data, and Tukey's test at p < 0.05 was then run. PTX, TQ, and their combinations inhibited MDA-MB-231cell proliferation and viability dose-dependently. TQ reduced the effective concentration (IC50) of PTX in co-treatment groups. PTX and TQ showed antagonistic effects when cell proliferation declined above 70%. Antagonistic effects shifted into additive and synergistic effects upon increasing PTX concentration, indicated by diminished cell proliferation below 70%. PTX-TQ co-treatment significantly enhanced P53 and BAX expression while reducing Bcl-2 expression. Also, their combination increased Beclin-1, ATG-5, and ATG-7 expression in treated cells. CONCLUSION: Effective concentrations of TQ and PTX had synergic effects and inhibited breast cancer cells via prompting apoptosis and autophagy in vitro.

Resveratrol-loaded decellularized ovine pericardium: ECM introduced for tissue engineering.

An ideal scaffold for skin tissue engineering should have a suitable potential for antibacterial activity, no hemolysis, sufficient porosity for air exchange, water retention capacity, and a suitable swelling rate to maintain tissue moisture. Considering this issue, our study used decellularized ovine pericardial tissue's extracellular matrix (ECM). These scaffolds were decellularized with sodium dodecyl sulfate (SDS) and sodium deoxycholate (SD) detergents along with vacuum methods. Following imaging with scanning electron microscopy (SEM), analysis of the mechanical properties, and the measurement of the amount of DNA, collagen, and glycosaminoglycan (GAG), our study observed that the three-dimensional (3D) structure of ECM was largely preserved. Resveratrol (RES) 400 µg/µL was loaded into the above scaffold, and analysis revealed that scaffolds containing RES and with vacuum reported higher antibacterial properties, a higher swelling rate, and increased water retention capacity. The biocompatibility and hemocompatibility properties of the above scaffolds also reported a significant difference between methods of decellularization.

A hybrid construct of decellularized matrix and fibrin for differentiating adipose stem cells into insulin-producing cells, an optimized in vitro assessment.

The generation of insulin-producing cells (IPCs) is an attractive approach for replacing damaged ß cells in diabetic patients. In the present work, we introduced a hybrid platform of decellularized amniotic membrane (dAM) and fibrin encapsulation for differentiating adipose tissue-derived stem cells (ASCs) into IPCs. ASCs were isolated from healthy donors and characterized. Human AM was decellularized, and its morphology, DNA, collagen, glycosaminoglycan (GAG) contents, and biocompatibility were evaluated. ASCs were subjected to four IPC differentiation methods, and the most efficient method was selected for the experiment. ASCs were seeded onto dAM, alone or encapsulated in fibrin gel with various thrombin concentrations, and differentiated into IPCs according to a method applying serum-free media containing 2-mercaptoethanol, nicotinamide, and exendin-4. PDX-1, GLUT-2 and insulin expression were evaluated in differentiated cells using real-time PCR. Structural integrity and collagen and GAG contents of AM were preserved after decellularization, while DNA content was minimized. Cultivating ASCs on dAM augmented their attachment, proliferation, and viability and enhanced the expression of PDX-1, GLUT-2, and insulin in differentiated cells. Encapsulating ASCs in fibrin gel containing 2 mg/ml fibrinogen and 10 units/ml thrombin increased their differentiation into IPCs. dAM and fibrin gel synergistically enhanced the differentiation of ASCs into IPCs, which could be considered an appropriate strategy for replacing damaged ß cells.

Accelerated wound healing with resveratrol-loaded decellularized pericardium in mice model.

One of the key objectives of regenerative medicine is the design of skin tissue engineering scaffolds to promote wound healing. These scaffolds provide a fresh viewpoint on skin injury repair by emulating body tissues in their structure. A suitable platform for cellular processes can be provided by natural scaffolds made from decellularized tissues while retaining the primary components. Resveratrol (RES), which has qualities like angiogenesis, antioxidant, antibacterial, and anti-inflammatory, is also useful in the healing of wounds. In this investigation, RES-loaded decellularized sheep pericardium scaffolds were created and tested on full-thickness wounds in a mouse model. According to the in vivo findings, the groups in which the wound was treated with decellularized pericardium (DP) had better wound healing than the control group and showed more production of angiogenic and anti-inflammatory substances. The secretion of these factors was greater in RES-loaded decellularized pericardium (DP-RES) than in the scaffold without RES, and the macroscopic and histological data supported this. Therefore, the use of decellularization scaffolds with substances like RES for the regeneration of skin wounds can be further researched and evaluated in the preclinical stages.

Decellularized kidney capsule as a three-dimensional scaffold for tissue regeneration.

Tissue regeneration is thought to have considerable promise with the use of scaffolds designed for tissue engineering. Although polymer-based scaffolds for tissue engineering have been used extensively and developed quickly, their ability to mimic the in-vivo milieu, overcome immunogenicity, and have comparable mechanical or biochemical properties has limited their capability for repair. Fortunately, there is a compelling method to get around these challenges thanks to the development of extracellular matrix (ECM) scaffolds made from decellularized tissues. We used ECM decellularized sheep kidney capsule tissue in our research. Using detergents such as Triton-X100 and sodium dodecyl sulfate (SDS), these scaffolds were decellularized. DNA content, histology, mechanical properties analysis, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), biocompatibility, hemocompatibility and scanning electron microscope (SEM) imaging were measured. The results showed that the three-dimensional (3D) structure of the ECM remained largely intact. The scaffolds mentioned above had several hydrophilic properties. The best biocompatibility and blood compatibility properties were reported in the SDS method of 0.5%. The best decellularization scaffold was introduced with 0.5% SDS. Therefore, it can be proposed as a scaffold that has ECM like natural tissue, for tissue engineering applications.

Exosome-loaded decellularized tissue: Opening a new window for regenerative medicine.

Mesenchymal stem cell-derived exosomes (MSCs-EXO) have received a lot of interest recently as a potential therapeutic tool in regenerative medicine. Extracellular vesicles (EVs) known as exosomes (EXOs) are crucial for cell-cell communication throughout a variety of activities including stress response, aging, angiogenesis, and cell differentiation. Exploration of the potential use of EXOs as essential therapeutic effectors of MSCs to encourage tissue regeneration was motivated by success in the field of regenerative medicine. EXOs have been administered to target tissues using a variety of methods, including direct, intravenous, intraperitoneal injection, oral delivery, and hydrogel-based encapsulation, in various disease models. Despite the significant advances in EXO therapy, various methods are still being researched to optimize the therapeutic applications of these nanoparticles, and it is not completely clear which approach to EXO administration will have the greatest effects. Here, we will review emerging developments in the applications of EXOs loaded into decellularized tissues as therapeutic agents for use in regenerative medicine in various tissues.

Stem cell induction and plant regeneration are affected by medium components in maca (Lepidium meyenii Walp).

BACKGROUND: In medicinal plants, selection, reproduction and preservation of important genotypes are very necessary. Nowadays, using tissue culture and regeneration techniques of medicinal plants under in vitro conditions has been able to proliferate medicinal plants widely, which is much higher than traditional methods of vegetative propagation. Maca (Lepidium meyenii), is an industrial plant whose root is the usable part. Maca has valuable medicinal effects such as sexual enhancement and reproductive power, infertility treatment, improved sperm count and quality, anti-stress, osteoporosis prevention and more. METHODS AND RESULTS: This study was conducted to induce callus and regeneration of Maca. First, MS medium supplemented with different concentrations of Kinetin, Naphthaleneacetic acid and 2,4-Dichlorophenoxyacetic acid [0.5, 1 and 2 µM respectively] and control were compared for callus induction from root and leaves. After 38 days of incubation, the first callus appeared, after 50 days of callus induction and after 79 days regeneration occurred. The callus induction experiment was performed for the study of the effect of three explants (leaf, stem and root) and seven hormone levels. The regeneration experiment was carried out by studying the effect of three explants (leaf, stem and root) on eight levels of the hormone. The results of data analysis on callus induction showed that the effects of explants, hormones and their interactions on callus induction percentage were highly significant but not significant on callus growth rate. The results of regression analysis showed that explants, hormones and their interactions had no significant effect on regeneration percentage. CONCLUSION: Based on our results, the best medium for inducing callus was Hormone 2,4-D [2 µM] and Kinetin [0.5 µM], in which the highest percentage of callus induction was in leaf explants (62%). And the lowest were in stem (30%) and root (27%) explants. According to the comparison of the mean, the best environment for regeneration of the environment was 4 µM 6-Benzylaminopurine 2.5 + Thidiazuron, in which the highest percentage of regeneration was in leaf explant (87%) and stem (69%) and the lowest in root explant (12). %).

The anti-cancer effect of resveratrol nano-encapsulated supplements against breast cancer via the regulation of oxidative stress.

AIM: Several shreds of evidence have supported the growth-inhibitory effect of resveratrol in breast cancer. Owing to the low efficiency, we aimed to fabricate an ACN nanoparticle containing resveratrol to target the proliferation of breast cancer cells. METHODS: Resveratrol encapsulation was characterized using spectrophotometry, FTIR, and SEM. The cytotoxicity and antioxidant activities of compounds were evaluated by MTT, NO, FRAP, and qRT-PCR assays on MCF7 and SKBr3 cells. RESULTS: Our result found that the encapsulation efficiency was 87%, the particle size was 200 ± 15 nm, and the zeta potential was 31 ± 0.4 mV. The prepared RES + ACN had controlled in vitro release. RES + ACN nanoparticle showed a significantly increased cytotoxicity in both cell lines. The reduced level of NO and enhance antioxidative content in both cells, especially the MCF7, were in line with increased expression of Nrf2 and SOD as well as more apoptotic effect. CONCLUSION: Decreased growth and increased expression of Nrf2 in MCF7 compared to SKBr3 cells proved that the upregulation of Nrf2 by nanoresveratrol is likely contributed to its relationship with ER/PR signaling factors, albeit its precise mechanism is needed to be more elucidated.

A novel 3D-electrospun nanofibers-scaffold grafted with Royal Jelly: improve hydrophilicity of the nanofibers-scaffold and proliferation of HUVEC cell line.

Tissue engineering is one of the most important medical rehabilitation tools that includes two vital components of scaffolding and cell growth stimulants. Therefore, designing a more intelligent, portable, monitorable, and safe scaffold that can release growth factors is a key step in achieving an acceptable level of cells for treating patients. In this study, a nanofibers-grafted scaffold was prepared with two-nozzle electrospinning to serve as a tissue engineering scaffold. Fundamental physical characterizations were carried out by scanning electron microscopy (SEM), pore diameter determination, and FT-IR. Fundamental physical characterization revealed that the nanofibers-scaffolds grafted with Royal Jelly significantly increased hydrophilicity, but the porosity of the novel-nanofibers did not alter significantly than the nanofibers without Royal Jelly. Based on the MTT assay results, cell growth, survival, and proliferation of the HUVEC Cell line were increased in the nanofibers scaffold grafted with Royal Jelly. Together, these findings highlight the potential of our novel scaffold for tissue engineering applications.

Nrf2 antioxidant pathway and apoptosis induction and inhibition of NF-κB-mediated inflammatory response in human prostate cancer PC3 cells by Brassica oleracea var. acephala: An in vitro study.

BACKGROUND: Brassica oleracea var. acephala is a good source of health-promoting biologically active compounds like phenolics, vitamins, and glucosinolates. METHODS AND RESULTS: This in vitro research was conducted to evaluate the apoptotic, antioxidant, anti-inflammatory, and antiproliferative properties of ethanolic extract of Brassica oleracea var. acephala (EEBO) in PC3 prostate cancer cells. The LC-MS/MS technique was applied to identify the biomolecules of EEBO. The MTT assay was used to evaluate the cytotoxic effects of EEBO on PC3 cells. Moreover, qRT-PCR was used to examine the expression levels of Nrf2, NQO1, HO-1, NF-κB, TNF-α, IL-6, BAX, and BCL-2 in PC3 cell line. MMP was predicted by Rhodamine 123 staining, and release of cytochrome c was detected by an ELISA kit. Further, apoptosis was quantified by DNA fragmentation assay. The Western blotting method was used to detect the protein expression levels, and The DPPH assay was applied to determine the antioxidant effect of EEBO. The formula and structure of 19 biomolecules were predicted by LC-MS/MS. EEBO exhibited scavenging activity for DPPH. The MTT test showed EEBO reduced the viability of PC3 cells. The mRNA and protein levels of NRF2 pathway genes and BAX were increased, but those of the NF-κB pathway genes and BCL-2 were decreased in the EEBO-treated cells. Moreover, EEBO led to the diminution of MMP and enhanced the release of cytochrome c and DNA fragmentation, which resulted in apoptosis. CONCLUSIONS: Molecular changes due to the anticancer impact of EEBO on PC3 were involved in the induction of Nrf2 antioxidant pathway and apoptosis and inhibition of inflammation.

L-proline as a novel additive to cryopreservation media improved post-thaw quality of human spermatozoon via reducing oxidative stress.

Sperm cryopreservation as a routine technique in assisted reproductive technique (ART) laboratories has detrimental effects on spermatozoa. Various methods have been introduced to improve it. The aim of this research was to evaluate the effects of L-proline supplementation in cryopreservation medium on normozoospermic semen samples. A total of 30 semen samples were collected from normozoospermic men. Cryopreservation media were supplemented with different concentrations of L-proline (0, 1, 2 and 4 mmol/L). The semen samples were cryopreserved. After thawing, sperm parameters and chromatin integrity (aniline blue (AB), toluidine blue (TB), sperm chromatin dispersion test (SCD) and chromomycin A3 (CMA3)), reactive oxygen species (ROS), and total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were evaluated. A total of 4 mmol/L L-proline significantly improved progressive motility and viability (p < 0.05). MDA and ROS levels significantly diminished in samples were cryopreserved by 4 mmol/L L-proline supplemented cryopreservation media (p < 0.001). Also, it significantly increased TAC level. Also, chromatin damages (AB, TB and CMA3) significantly improved in samples were cryopreserved by 4 mmol/L L-proline supplemented cryopreservation media (p < 0.05). The results support that the usage of L-proline supplemented cryopreservation media to improve sperm quality after cryopreservation.

Beneficial effect of L-Proline supplementation on the quality of human spermatozoa.

L-Proline is a natural anti-oxidative and osmoprotectant agent, playing a versatile role in cell metabolism and physiology. The present study aimed to explore the antioxidant effects of L-Proline on human sperm function during incubation. Thirty healthy, normozoospermic men (27-40 years) were enrolled. Sperm samples were incubated in an unsupplemented sperm medium (control group), or supplemented with L-Proline (1, 2 and 4 mmol/L) to evaluate its effect during 0, 1, 4 and 24 h of incubation. Sperm were assessed in terms of motility, viability, morphology, chromatin and DNA integrity. Moreover, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined in the sperm medium. The results indicated that 2 mmol/L of L-Proline significantly improved the maintenance of sperm motility, viability, normal morphology, chromatin and DNA integrity, and TAC levels compared to the control group during 24 h of incubation (p < 0.05). However, 1 and 4 mmol/L of L-Proline could not significantly preserve sperm parameters, chromatin quality, and antioxidant status during different incubation times compared to the control group (p > 0.05). Collectively, the inclusion of L-Proline (2 mmol/L) in the human sperm medium maintains sperm parameters and chromatin quality probably by modulating the oxidative status.

Adipose tissue-derived stem cells: a comparative review on isolation, culture, and differentiation methods.

Adipose tissue-derived stem cells (ADSCs) are an available source of mesenchymal stem cells with the appropriate capacity to in vitro survive, propagate, and differentiate into cells from three lineages of ectoderm, mesoderm, and endoderm. The biological features of ADSCs depend on the donor physiology and health status, isolation procedure, culture conditions, and differentiation protocols used. Adipose tissue samples are provided by surgery and lipoaspiration-based methods and subjected to various mechanical and chemical digestion techniques to finally generate a heterogeneous mixture named stromal vascular fraction (SVF). ADSCs are purified through varied cell populations that exist within SVF and cultured under standard conditions to give rise to a highly rich resource of stem cells directly applied in the clinic or differentiated into a wide range of cells. The development and optimization of conventional isolation, expansion, and differentiation methods seem noteworthy to preserve the desirable biological functions of ADSCs in pre-clinical and clinical investigations.

Functional survey of decellularized tissues transplantation for infertile females.

Numbers of women worldwide face infertility, which will have a significant impact on a couple's life. As a result, assisting with the treatment of these individuals is seen as a critical step. Successful births following uterus and ovary donation have been reported in recent. When immunosuppressive drugs are used in patients who receive donated tissues, there are always problems with the drugs' side effects. In recent years, tissue engineering has mainly been successful in treating infertility using decellularization techniques. Engineered uterus and ovary prevent immunological reactions and do not require immunosuppressive drugs. The most important aspect of using decellularized tissue is its proper function after transplantation. These tissues must be able to produce follicles, secrete hormones and cause pregnancy. This study aimed to investigate research on decellularized tissues and transplanted into the female reproductive system. In this study, just tissues that, after transplantation, have the proper function for fertility were investigated.

Ceratonia siliqua (Carob) extract improved in vitro development of vitrified-warmed mouse germinal vesicle oocytes: assessment of possible mechanism.

Oocyte banking is a vital step for safekeeping and spreading genetic resources of animals. It is also used for fertility preservation of human. Oocyte vitrification is closely related to the lower developmental competence which includes the cryo-injury arisen during vitrification. The aim of the present study was to evaluate the maturation, embryonic development and production of reactive oxygen species (ROS) of mice oocytes following the supplementation vitrification media with different concentrations of Ceratonia siliqua (carob) extracts. In this experimental study, germinal vesicle oocytes collected from 8 to 10 week-old female NMRI mice (30-40 gr) were randomly divided into six groups of vitrification media supplemented with 0 (control), 5, 10, 20, 30 and 50 µg/ml C. siliqua. After thawing, oocytes were put in an in vitro maturation medium (IVM) (α-MEM: Alpha Minimum Essential Medium). 3-4 and 24 h (hr) later, the oocyte nuclear maturity was checked. Standard in vitro fertilization was performed on the matured oocytes (MII), and embryonic development was followed. Extra- and intra-cellular ROS was measured in IVM medium after 24 h of oocyte incubation. The addition of 20 and 30 µg/ml C. siliqua extract to vitrification media improved normal morphology of warmed germinal vesicle (GV) oocytes, rate of germinal vesicle break down (GVBD), and metaphase 2 (MII) oocyte formation significantly (p < 0.05). Fertilization rate, (embryonic development to 2 cells stage, 4-8 cells stage, and > 8 cells stage increased in the 30 µg/ml C. siliqua group significantly (p < 0.05). Furthermore, supplementation of 30 µg/ml C. siliqua in vitrification media significantly decreased extra- and intra-cellular of ROS as well as embryonic fragmentation (p < 0.05). In conclusion, supplementation of GV oocyte vitrification media with carob extract improved maturation, fertilization, and embryonic development rate and decreased extra- and intra-cellular ROS levels.

Novel therapeutic approaches of tissue engineering in male infertility.

Male reproductive organ plays an important role in sperm production, maintenance and entry to the female reproductive tract, as well as generation and secretion of male sex hormones responsible for the health of male reproductive system. The purpose of this paper is to discuss the experimental and clinical evidence on the utilization of tissue engineering techniques in treating male infertility. Tissue engineering (TE) and regenerative medicine have developed new approaches to treat patients with reproductive disorders such as iatrogenic injuries, congenital abnormalities, and trauma. In some cases, including congenital defects and undescended testis or hypogonadism, the sperm samples are not retrieved. This makes TE a possible future strategy for restoration of male fertility. Here, we have summarized the recent advances in experimental and clinical application of cell-, tissue-, and organ-based regenerative medicine in male reproductive disorders.

Review on Metal-Based Nanoparticles: Role of Reactive Oxygen Species in Renal Toxicity.

The rapidly emerging field of nanotechnology has offered innovative discoveries. Due to a wide variety of nanotechnology applications in the industrial, medical, and consumptive products, the application of nanotechnology has received considerable attention in the past decades. Metal-based nanoparticles including metal and metal oxide nanoparticles are now widely utilized in different areas of nanotechnology, leading to an increase in human exposure to nonmaterial. Since the kidney is one of the major organs to remove a variety of potentially harmful substances, including nanoparticles (NPs), from living organisms and a large proportion of cardiac output reaches the kidney, this organ is susceptible to the toxin-induced renal injury. However, despite the extensive use of NPs, there is still a limited understanding of NP-mediated toxicity. The unique physicochemical properties of metal-based NPs not only make them highly desirable in a variety of applications but also enable them to induce changes at biological levels of cellular activities, including reactive oxygen species (ROS) generation. Since oxidative stress is a key factor of NP-induced injury, it is urgent to characterize the ROS response resulting from metal-based NPs. This review summarizes an assessment of the signaling pathways that are involved in the metal-based NP-induced nephrotoxicity, with a particular focus on ROS production along with the potential oxidative stress-dependent mechanism. However, available data show that metal-based NPs may have a severe impact on the renal system, but the exact molecular mechanism of nephrotoxicity is not fully understood. A highly effective strategy for a better understanding of the mechanism would be to collect an increasing volume of information about the exposure time, physicochemical characteristics of the engineered NPs, and the cellular effects. In order to achieve a thorough knowledge of ROS-dependent renal toxicity, both in vitro and in vivo studies should be considered.

Cryoprotective effect of sericin supplementation in freezing and thawing media on the outcome of cryopreservation in human sperm.

The destructive effects of sperm cryopreservation result in decreased sperm parameters and their fertilizing ability. Antioxidants supplementation can potentially improve cryopreservation outcomes. In this study, we tried to investigate the effects of sericin supplementation in freezing and thawing media on frozen-thawed human sperm motility, morphology, viability, and DNA fragmentation. In experiment 1, semen samples were collected from 30 healthy fertile men and were cryopreserved in the presence of freezing medium supplemented with different concentrations of sericin (0, 0.5, 1, 2.5, and 5%). The results showed that the addition of 2.5 and 5% sericin in freezing medium significantly increased sperm viability and total motility (A + B) and decreased DNA fragmentation (P < 0.05). In experiment 2, semen samples were collected from 21 fertile men and were cryopreserved in freezing medium without any supplementation for 48 h. Then, the samples were thawed in medium supplemented with different concentrations of sericin (0, 0.5, 1, 2.5, and 5%). The addition of 5% sericin to thawing medium increased the total motility, viability, and decreased DNA fragmentation compared with those in thaws without sericin. In nutshell, the results clearly indicate the feasibility of sericin as an cryoprotective supplement for freezing media in human spermatozoa.

In vitro effects of clomiphene citrate on sperm parameters and fertilisation rate in male NMRI mice.

Clomiphene citrate (CC), as a medication in male infertility, improves the sperm parameters in oral consumption but various detrimental side effects have been reported including testicular tumours, gynaecomastia, skin allergic reactions and ocular symptoms. Therefore, this study was designed to evaluate the in vitro effects of CC on sperm parameters and fertilisation rate in IVF protocol. Sperm samples of NMRI adult mice were divided into six groups: group 1 received no treatment (control group), while groups of 2, 3, 4, 5 and 6 (experimental groups) were incubated with the doses of 0.001, 0.01, 0.1, 1 and 10 µg/ml of CC in culture medium respectively. Sperm parameters (viability, morphology and motility), DNA fragmentation levels and fertilisation rate in IVF were evaluated. The results demonstrated that the doses of 0.1 µg/ml (p = .000007 for viability and p = .00006 for fertilisation rate) and 1 µg/ml (p = .032 for viability and p = .005 for fertilisation rate) CC cause a significant improvements; also, the dose of 0.1 µg/ml CC found effective on sperm motility (p = .0003). In the field of IVF, the application of 0.1 and 1 µg/ml of CC in the culture medium may improve the sperm parameters in IVF protocol with no side effects.

The effects of hydroalcoholic extract of Vaccinium arctostaphylos L. on sperm parameters, oxidative injury and apoptotic changes in oxymetholone-induced testicular toxicity in mouse.

Anabolic androgenic steroids (AAS) such as oxymetholone (OM) used for athletic enhancement, but increased free radicals damage and changes in hormonal levels, lead to serious and irreversible organ damage. Vaccinium arctostaphylos(V. arctostaphylos( has been demonstrated to have antioxidant and antiinflammatory effects. The aim of present study was to investigate V. arctostaphylos effect on OM-induced oxidative injury in mouse testis and sperm parameters. In this experimental study, 30 BALB/c mice were divided into five groups, including healthy, positive control(5 mg/kg OM) and three treatment groups (100, 200 and 400 mg/kg of V. arctostaphylos extract + 5 mg/kg OM). At the end of the study, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were measured. Testis stereological and sperm parameters were calculated. Antioxidant status was measured using nitric oxide (NO) and FRAP assay, and malondialdehyde (MDA) levels. Furthermore, the expression of p53, caspase-3, Bax and Bcl-2 was measured. V. arctostaphylos decreased the serum level of testosterone, increased the LH and FSH, and improved the stereological and sperm parameters and down-regulated the p53, caspase-3 and Bax and up-regulated Bcl-2 genes. Furthermore, this dose decreased serum levels of NO and increased testis FRAP and MDA levels in treated groups compared with OM group. V. arctostaphylos extract has protective effects against testicular toxicity caused by OM.