The Potential Radioprotective Effect of Piperine against Radiation-Induced Lung Injury in Mice: Histopathological and Biochemical Evaluations.

INTRODUCTION: It has been hypothesized that piperine, the main alkaloid component of black pepper, possesses a unique radioprotective effect. This study aimed to investigate the protective effect of piperine against Radiation-Induced Lung Injury (RILI) in mice. METHOD: Firstly, eighty male mice were divided into eight groups; the control group did not receive any dosage of piperine and radiation (6 Gy), and the other groups received piperine alone at doses 10, 25, and 50 mg/kg, radiation, and radiation-piperine combination (6 Gy + 10, 25, and 50 mg/kg). Animals received piperine by gavage for 7 consecutive days. To investigate the effect of piperine pretreatment in mice that were exposed to radiation, histopathological and biochemical evaluations (markers of oxidative stress) were performed. Irradiation led to an increase in oxidative stress (increase in MDA and PC). Pretreatment of piperine in all three doses in irradiated mice was able to reduce oxidative stress compared to mice that were only exposed to radiation. RESULTS: Piperine at a dose of 25 mg/kg exhibited the highest protective effect as compared to other doses. Also, in the histopathological examination, it was seen that pretreatment with piperine was able to improve the infiltration of inflammatory cells and reduce the thickness of the alveolar septum and air sac damage. CONCLUSION: The outcomes completely proved significant lung protection by piperine in mice through reducing oxidative stress. This natural compound could be considered a protective agent against lung injury induced by ionizing radiation.

Insights into the development of 99mTc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies.

Serotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT1A), serotonin-2A (5-HT2A), 5-HT1A/7 heterodimers and serotonin receptor neurotransmitter (SERT). This review focuses on recent efforts in the design, synthesis and evaluation of 99mTc-radioligands used for single photon emission computerized tomography (SPECT) imaging of serotonergic (5-HT) receptors. Additionally, the discussion will cover aspects such as chemical structure, in vitro/vivo stability, affinity toward serotonin receptors, blood-brain barrier permeation (BBB), and biodistribution study.

Piperine mitigates oxidative stress, inflammation, and apoptosis in the testicular damage induced by cyclophosphamide in mice.

Although cyclophosphamide (CP) has been approved as an anticancer drug, its toxic effect on most organs, especially the testis, has been established. Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti-inflammatory activities. This study was investigated the protective effects of PIP on CP-induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB/c mice (30-35 g) were divided into six groups (n = 8), receiving normal saline (C), 5 mg/kg of PIP (PIP5), 10 mg/kg of PIP (PIP10), 200 mg/kg of CP, 200 mg/kg of CP + PIP5, and 200 mg/kg of CP + PIP10. On the eighth day of the study, blood and testis samples were prepared for serum testosterone hormone quantification, sperm analysis, histological, and immunohistochemical assays. The results of this study showed that CP induced testicular toxicity with the decrease of sperm count, motility, and viability. Also, CP treatment caused histological structure alterations in the testis, including exfoliation, degeneration, vacuolation of spermatogenic cells, and reducing the thickness of the epithelium and the diameter of the seminiferous tubule. In addition, CP decreased glutathione (GSH) levels, increased malondialdehyde (MDA) levels, Caspase-3, and NF-κB. At the same time, PIP treatment reduced testicular histopathological abnormalities, oxidative stress, and apoptosis that were induced by CP. These results showed that PIP improved CP-induced testicular toxicity in mice, which can be related to its antioxidant, antiapoptotic, and anti-inflammatory activities.

99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors.

BACKGROUND: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT7R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT7R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT7R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3(H2O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. RESULTS: Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-HT7R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT7R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT7R.

Radioprotective effect of piperine, as a major component of black pepper, against radiation-induced colon injury: biochemical and histological studies.

BACKGROUND: Patients undergoing radiotherapy are prone to radiation-induced gastrointestinal injury. Piperine is an alkaloid component in black pepper with a unique chemopreventive activity against oxidative stress-related damage in healthy tissues. The purpose of this study was to investigate the effects of piperine on intestinal damage. METHODS: In this study, mice were divided into eight groups: including the control, piperine (10, 25, and 50 mg/kg), radiation (6 Gy), and piperine+radiation (10, 25 and 50 mg/kg + 6 Gy) groups. The radioprotective effects of piperine were evaluated by biochemical (MDA, GSH, and PC) and histopathological assessments in colon tissues. RESULTS: The 10 mg/kg dose of piperine significantly reduced the levels of oxidative stress biomarkers compared to the group that received only radiation. In addition, pre-treatment with 10 mg/kg piperine diminished the histopathological changes like vascular congestion in the submucosa, while the dose of 50 mg/kg led to the infiltration of inflammatory cells. CONCLUSION: Based on this study, it is concluded that piperine, at low dose, with its antioxidant properties, could reduce the colon damage caused by radiation.

Sinapic acid attenuates cyclophosphamide-induced liver toxicity in mice by modulating oxidative stress, NF-κB, and caspase-3.

Objectives: Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Crosstalk between Oxidative Stress and Inflammation Induced by Ionizing Radiation in Healthy and Cancerous Cells.

Radiotherapy (RT) is a unique modality in cancer treatment with no replacement in many cases and uses a tumoricidal dose of various ionizing radiation types to kill cancer cells. It causes oxidative stress through reactive oxygen species (ROS) production or the destruction of antioxidant systems. On the other hand, RT stimulates the immune system both directly and indirectly by releasing danger signals from stress-exposed and dying cells. Oxidative stress and inflammation are two reciprocal and closely related mechanisms, one induced and involved by the other. ROS regulates the intracellular signal transduction pathways, which participate in the activation and expression of pro-inflammatory genes. Reciprocally, inflammatory cells release ROS and immune system mediators during the inflammation process, which drive the induction of oxidative stress. Oxidative stress or inflammation-induced damages can result in cell death (CD) or survival mechanisms that may be destructive for normal cells or beneficial for cancerous cells. The present study has focused on the radioprotection of those agents with binary effects of antioxidant and anti-inflammatory mechanisms in ionizing radiation (IR)-induced CD.

The preclinical study of 177Lu-DOTA-LTVSPWY as a potential therapeutic agent against HER2 overexpressed cancer.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has evolved in cancer therapy and diagnosis. LTVSPWY, as a peptide, can target HER2 receptor; on the other hand, 177Lu emits ß- which is helpful for cancer therapy. The radiolabeling of LTVSPWY with 177Lu results in a therapeutic agent (177Lu-DOTA-LTVSPWY) capable of cancer treatment. METHODS: 177Lu-DOTA-LTVSPWY was prepared with high radiochemical purity (RCP). The stability was investigated in saline and human serum. The radiotracer affinity toward the SKOV-3 cell line with overexpression of the HER2 receptor was evaluated. Then the impact of the radiotracer on the colony formation of the SKOV-3 cell line was investigated with colony assay. Moreover, the biodistribution of this radiotracer in SKOV-3 xenograft tumor-bearing nude mice were also studied to determine the radiotracer accumulation in the tumor site. The mice were treated with 177Lu-DOTA-LTVSPWY and subjected to histopathological evaluation. RESULTS: The RCP of 177Lu-DOTA-LTVSPWY after radiolabeling and stability tests was more than 97.7%. The radiotracer displayed high affinity toward the SKOV-3 cell line (KD = 6.6 ± 3.2 nM). Treatment of the SKOV-3 cell line with the radiotracer reduces the SKOV-3 colony survival to less than 3% for 5 MBq of the radiotracer. Tumor-to-muscle (T/M) ratio is the highest at 48 h and 1 h post-injection (2.3 and 4.75, respectively). The histopathological study also confirms the cellular damage to the tumor tissue. CONCLUSIONS: 177Lu-DOTA-LTVSPWY can recognize HER2 receptors in vivo and in vitro; hence, it can serve as a therapeutic agent.

Choosing the Right Protocol to Establish MCF-7 Tumor Xenograft in Nude Mice.

BACKGROUND: Xenografts of various human cancers in nude mice provide a helpful model in cancer research. This study aimed to develop a xenograft mouse model of MCF-7 breast cancer using injectable estradiol valerate. METHODS: Thirty healthy female C57 nu/nu mice were engrafted with three protocols to establish an MCF-7 tumor. Injectable estradiol valerate (10 mg/ml) was used as a substitute for estradiol pellets. The development of tumors was recorded daily, and data were statistically analyzed. Histology of bladder, kidney, and tumors was used to estimate tumor establishment and probable urinary adverse effects. RESULTS: According to the findings, the duration of MCF-7 tumor growth was the lowest for protocol B (tumor tissue). Also, this protocol had the highest xenograft yield within the shortest time duration (37 days for protocol B vs. 73 days for protocol A) without causing urinary adverse effects. CONCLUSION: Our findings revealed that estradiol valerate, which is way less expensive than estradiol pellets, can be used as a tumor proliferator to establish MCF-7 tumors with the highest yield when MCF-7 tumors have been used for xenograft.

Molecular Imaging of HER2 Expression in Breast Cancer patients Using the [99mTc] Tc-Labeled Small Peptide.

PURPOSE: The accurate determination of human epidermal growth factor receptor 2 (HER2) status can predict response to treatment with HER2-targeted therapy for HER2-positive breast cancer patients. [99mTc]Tc-HYNIC-(Ser)3-LTVPWY ([99mTc]Tc-HYNIC-LY) is a small synthetic peptide molecule targeting of the HER2 receptor. This clinical study evaluated the pharmacokinetic, dosimetry, and efficacy of [99mTc]Tc-HYNIC-LY for determining the HER2 status in primary breast cancer patients. MATERIALS AND METHODS: In total, 24 women with suspected primary breast cancer received an intravenous injection of approximately 20 µg (∼740 MBq) of [99mTc]Tc-HYNIC-LY. In the first 3 patients, blood levels of radioactivity were analyzed for pharmacokinetic evaluation and planar gamma camera imaging was conducted at 30 min and 1, 2, 4, and 24 hour after injection for dosimetry assessment. In the last 21 patients, planar imaging was performed at the baseline, as well as 1, 2, 3, and 4 hour, followed by single-photon emission computed tomography (SPECT) imaging after 4 hour to evaluate the tumor-targeting potential in primary lesions. RESULTS: Injection of [99mTc]Tc-HYNIC-LY was safe and well tolerated. Fast blood clearance provided high-contrast HER2 imaging within 1 to 4 hour. The highest absorbed radiation dose was found for kidneys (6.78E-03 ± 2.62E-04 mSv/MBq), followed by the heart (3.73E-03 ± 1.98E-04 mSv/MBq). The [99mTc]Tc-HYNIC-LY peptide was able to detect HER2 status in primary tumors at an acceptable level. CONCLUSION: The findings of this study indicated that [99mTc]Tc-HYNIC-LY SPECT is safe and feasible for the identification of HER2-positive lesions in primary breast cancer patients, and may provide an accurate and non-invasive modality for guiding HER2 targeted therapy.

The Effects of Zataria multiflora Cream on Split-Thickness Skin Graft Donor-Site Management: A Randomized, Blinded, Placebo-Controlled Study.

Purpose: The wound healing process involves a complex series of biological events. Skin grafts have several uses as a reconstructive method. There are several dressings for the skin graft donor site, but the optimum dressing agents that provide all the requirements at the same time are unclear. This prospective, randomized, placebo-controlled clinical trial aimed to evaluate the therapeutic effect of Zataria multiflora cream in the wound healing process of partial-thickness skin graft donor sites and compared it with a placebo. Materials and Methods: This clinical trial study was performed on patients who underwent split-thickness skin grafts. Enrolled patients applied Z. multiflora cream and placebo controlled (petrolatum ointment) twice a day, from the day of intervention at the skin graft donor sites in two parts, separately. On 7, 14, 21, and 28 days after surgery, the wound healing process was evaluated, photographed, and scored according to the Bates-Jensen assessment tool. Evidence of infection was evaluated. The main agent and placebo were compared during the wound healing process. Results: Decreases in wound surface area and total score were significantly greater in the Z. multiflora group (p < 0.05). The wounds of 30% of patients in the second week and 90% of patients in the third week were completely epithelialized in the Z. multiflora group. These values were 3.3% and 36.7% for the control group, respectively, and so, the healing rate was ∼9-fold in the second week and 2.45-fold in the third week in the Z. multiflora group compared with the control group (p < 0.05). Conclusion: Wound healing and reepithelialization accelerated significantly in the first, second, third, and fourth week after intervention in the Z. multiflora treatment group, due to modulating the inflammatory phase and improving the proliferative phase. Clinical Trial Registration Number: IRCT20210624051695N1.

Homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide improved HER2-overexpressed tumor targeting and imaging.

We hypothesized that a novel design of the LTVPWY (LY) peptide might exhibit a great potential for improving binding affinity and targeting HER2-overexpressed tumors. Hence, new dimer construction of 99mTc-labeled LY [99mTc-HYNIC-E(SSSLTVPWY)2] (99mTc-DLY) was introduced. Afterward, a head-to-head comparison of in vitro and in vivo experiments was performed between 99mTc-DLY and 99mTc-HYNIC-SSSLTVPWY as the monomer analog. The blocking dosage of trastuzumab reduced the uptake of the dimer about 20% more efficiently than the monomer in the SKOV-3 cell line. A twofold increase in competitive binding affinity and biological half-life was observed for 99mTc-DLY. The ovarian-tumor-bearing mice were detected with high contrast where the tumor-to-muscle ratio of 99mTc-DLY was notably increased about 40% using a gamma camera. The biodistribution experiment revealed an approximately 10% enhancement in tumor/blood, tumor/muscle, and tumor/bone ratios for the dimer. More rapid blood clearance was another achievement of the homodimer design. Overall, 99mTc-DLY successfully affected the pharmacokinetics and consequently the visualization of HER2-overexpressing tumors.

Radioprotective effects of gliclazide against irradiation-induced cardiotoxicity and lung injury through inhibiting oxidative stress.

Radiotherapy is one of the main treatments for localized primary cancer in patients. Cardiotoxicity and lung injury are two of the main side effects of oxidative stress following radiotherapy in patients with thoracic region cancer. Gliclazide (GLZ) as an antihyperglycemic drug has antioxidant, anti-inflammatory, and anti-apoptotic activities. This study aimed to evaluate the effect of GLZ in cardiotoxicity and lung injury induced by irradiation (IR). In this experimental study, 64 mice were divided into eight groups: control, GLZ (5, 10, and 25 mg/kg), IR (6 Gy), and IR + GLZ (in three doses). GLZ was administrated for 8 consecutive successive days and mice were exposed with IR on the 9th day of study. On the 10th day of study, tissue biochemical assay and at 14th day of study, histopathological assay were performed to evaluate for cardiotoxicity and lung injury. The findings revealed that IR induces atypical features in heart and lung histostructure, and oxidative stress (an increase of MDA, PC levels, and decrease of GSH content) in these tissues. GLZ administration preserved heart and lung damages and improves oxidative stress markers in mice. Data have authenticated that GLZ could protect heart and lung histostructure against oxidative stress-induced injury through inhibiting oxidative stress.

Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.

It is demonstrated that fasting can alter the biodistribution of radiopharmaceuticals in nuclear medicine. Various studies have highlighted that fasting is interpreted to be easy for physicians during PET study, fasting is one of the most important factors determining the usefulness of this protocol. It is well documented that fasting can suppress normal 18F-FDG PET uptake during nuclear cardiology. However, there is no consensus about the usefulness of fasting on radiopharmaceuticals, especially on 18F-FDG in PET imaging, but special attention should be paid to the setting of the fasting duration. Nevertheless, it does seem we still need extensive clinical studies in the future. The present study aims to review the various aspects of fasting, especially metabolic alteration on radiopharmaceutical biodistribution. In this study, we focused more on the effect of fasting on 18F-FDG biodistribution, which alters its imaging contrast in cardiology and cancer imaging. Therefore, shifting substrate metabolism from glucose to free fatty acids during fasting can be an alternative approach to suppress physiological myocardial uptake.

Initial preclinical evaluation of 68 Ga-DOTA-(Ser) 3 -LTVSPWY peptide as a PET radiotracer for glioblastoma targeting and imaging.

PURPOSE: Imaging of glioblastoma multiform (GBM) tumor using 68 -Galium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid-Ser-Ser-Ser-Leu-Thr-Val-Ser-Pro-Trp-Tyr ( 68 Ga-DOTA-(Ser)3-LTVSPWY) as a PET radiotracer for HER2 receptor due to fact that this receptor plays a pivotal role in the tumorigenesis and tumor progression in a wide range of cancer. METHODS: 68 Ga-DOTA-(Ser) 3 -LTVSPWY was produced with high radiochemical purity. The affinity and specificity of this radiotracer toward HER2 receptor on the surface of glioma glioblastoma (U-87 MG) cell line were evaluated. Furthermore, the biodistribution and PET imaging of this radiolabeled peptide were investigated on xenografted U-87 MG tumor-bearing mice. RESULTS: The in-vitro specific binding study revealed that the 68 Ga-DOTA-(Ser) 3 -LTVSPWY binds to different cell lines with respect to their level of HER2 expression. The calculated K D and B max of radiolabeled peptide toward U-87 MG cell line were 5.5 ± 2.4 nmol/l and (2.4 ± 0.3) × 10 5 receptors per cell, respectively. The highest tumor uptake was observed at 30-min postinjection, whereas the tumor-to-muscle ratio was about four-fold. The acquired PET images distinctively show tumor site, which was blocked with excess nonlabeled peptide that revealed specific in-vivo targeting of 68 Ga-DOTA-(Ser) 3 -LTVSPWY for glioma. CONCLUSION: 68 Ga-DOTA-(Ser) 3 -LTVSPWY specifically recognizes HER2 receptors and could be a potential candidate for GBM imaging.

Homomultimer Strategy for Improvement of Radiolabeled Peptides and Antibody Fragments in Tumor Targeting.

A homomultimeric radioligand is composed of multiple identical ligands connected to the linker and radionuclide to detect a variety of overexpressed receptors on cancer cells. Multimer strategy holds great potential for introducing new radiotracers based on peptide and monoclonal antibody (mAb) derivatives in molecular imaging and therapy. It offers a reliable procedure for the preparation of biological-based targeting with diverse affinities and pharmacokinetics. In this context, we provide a useful summary and interpretation of the main results by a comprehensive look at multimeric radiopharmaceuticals in nuclear oncology. Therefore, explanations for the strategy mechanisms and the main variables affecting the biodistribution results will be explained. The discussion is followed by highlights of recent work in the targeting of various types of receptors. The consequences are expressed based on comparing some parameters between monomer and multimer counterparts in each relevant section.

The Influence of Kidneys Ion Transport Inhibitors on the Pharmacokinetic and Tumor Uptake Behaviors of a HER2-targeted Small Size Radiolabeled Peptide.

BACKGROUND: HER2 over-expression plays a crucial role in the cancer treatment protocol. This study evaluates the effectiveness of organic anion and cation transport inhibitors and substrate on the tumor uptake of 99mTc- HYNIC-(Ser)3-LTVPWY radiotracer in SKOV-3 tumor-bearing nude mice. METHODS: Before the injection of the radiolabeled peptide, SKOV-3 tumor-bearing nude mice were treated with furosemide, cimetidine, para-amino hippuric acid, and saline. The inhibition effects of the organic anion and cation transport inhibitors were compared with the control group. In both treatment and control groups, the tumor and renal accumulation of radiopeptide in mice bearing SKOV-3 tumors were assessed in biodistribution and SPECT imaging studies. RESULTS: The biodistribution and imaging results suggested that all treated groups showed a higher tumor and higher normal tissue radioactivity compared to the control group. According to the tumor imaging study, the furosemidetreated group had slightly better tumor uptake and a higher tumor to muscle uptake ratio than other treatment groups. CONCLUSION: Administration of furosemide (an OAT inhibitor) increased radioactivity accumulation in the kidneys and blood and improved tumor radioactivity uptake. PAH (an anion transporter substrate) and cimetidine (an OCT inhibitor) have a minor effect on the accumulation of radioactivity in the kidneys and the acquired images.

Mefenamic acid as a promising therapeutic medicine against colon cancer in tumor-bearing mice.

Although radiotherapy is an effective strategy for cancer treatment, tumor resistance to ionizing radiation (IR) and its toxic effects on normal tissues are limiting its use. The aim of this study is to evaluate the anti-cancer effects of mefenamic acid (MEF), as an approved medicine, and its combination with IR against colon tumor cells in mice. Tumor-bearing mice were received MEF at a dose of 25 mg/kg for 6 successive days. The tumor size was measured. In the second experiment, after MEF treatment, tumor-bearing mice locally received an X-ray at dose 6 Gy. Tumor growth and biochemical, histological, and immunohistological assay (caspase-3) were performed. MEF significantly decreased tumor size in mice in comparison to the control group. IR and/or MEF treatment significantly reduced the tumor volume and inhibited tumor growth by 49%, 55%, and 67% by MEF, IR, and MEF + IR groups as compared with the control group. Administration of MEF in combination with radiation had a synergistic effect on enhanced histopathological changes in tumor tissues. MEF treatment in IR exposure mice showed a significant increase in the immunoreactivity of caspase-3 in the colon tumor tissue. MEF has an anti-tumor effect in colon tumor-bearing mice. MEF in combination with IR increased pathological changes and apoptosis in tumor tissues, suggesting that MEF might be clinically useful in the treatment of colon cancer.

Radioprotective Effect of Febuxostat Against Testicular Damage Induced by Ionizing Radiation in Mice.

BACKGROUND: The testis is one of the most radiosensitive tissues in pelvic radiotherapy, especially in prostate cancer. Febuxostat (FBX), as an inhibitor of xanthine oxidase, has anti-inflammatory, antioxidant, and anti-apoptosis properties. OBJECTIVES: The aim of this research was to survey the protective effect of FBX against irradiation (IR)-induced testis damage via the attenuation of oxidative stress. METHODS: Male adult mice were randomly assigned into eight groups: control, FBX with three doses of 5, 10, and 15 mg/kg, IR with 6 Gy, IR + FBX (IR + FBX in three doses), respectively. In the IR + FBX groups, FBX was administrated for 8 consecutive days, and then mice were exposed to IR at a dose of 6 Gy on the 9th day. One day after irradiation, biochemical parameters were evaluated in the testis of animals, while histopathological assessment had been performed on 14th day. RESULTS: Irradiation led to the induction of testicular toxicity. FBX significantly protected histopathological alterations and decreased oxidative stress parameters in irradiated testis. Besides, FBX increased the diameter and germinal epithelial thickness of seminiferous tubules and Johnson's score in irradiated mice. CONCLUSION: Data showed that FBX markedly protected testicular injury induced by IR by inhibiting oxidative stress and may be considered as an infertility inhibitor in cancer patients, especially prostate cancer.