Alpha-lipoic acid enhances ischemic postconditioning-mediated improvement of myocardial infarction and apoptosis in diabetic rats with ischemia/reperfusion injury.

This work evaluated the combined effects of alpha-lipoic acid (ALA) and ischemic postconditioning (Post) on myocardial infarction and cell death in rats with chronic type-II diabetes following ischemia/reperfusion injury. The rats received a high-fat diet and were given one intraperitoneal injection of 35 mg/kg streptozotocin to induce chronic diabetes. They were then pretreated with ALA (100 mg/kg/day, orally) for 5 weeks before undergoing ischemia/reperfusion (I/R) insult. The hearts experienced 35 min regional ischemia through ligating the left anterior descending coronary artery, followed by 60 min reperfusion. The Post protocol involved 6 cycles of a 10/10 s algorithm, applied during the early stage of reperfusion. The use of Post alone did not significantly alter lactate dehydrogenase and infarct size levels, while ALA showed positive effects. Similar findings were observed for apoptotic changes with single treatments. However, the concurrent administration of ALA and Post significantly reduced the protein expressions of Bax, Bax/Bcl2, and cleaved caspase-3 while increasing Bcl2 expression. Additionally, the histopathological findings of the combined therapy were superior to those of single treatments. The concomitant use of ALA and Post effectively inhibited apoptosis, leading to cardiac recovery after I/R injury in diabetic conditions. This strategy could improve outcomes for preserving diabetic hearts following I/R insults.

Effect of troxerutin on the expression of genes regulating mitochondrial biogenesis and microRNA-140 in doxorubicin-induced testicular toxicity.

Background: Application of doxorubicin (DOX) in cancer patients is limited due to its dose-dependent toxicity to nontarget tissues such as testis and subsequent infertility. Due to limitation of our knowledge about the mechanisms of DOX toxicity in the reproductive system, reduction of DOX-induced testicular toxicity remains an actual and primary clinical challenge. Considering the potentials of troxerutin (TXR) in generating a protective phenotype in many tissues, we aimed to examine the effect of TXR on DOX-induced testicular toxicity by evaluating the histological changes and the expression of mitochondrial biogenesis genes and microRNA-140 (miR-140). Materials and Methods: Twenty-four adult male Wistar rats (250-300 g) were divided in groups with/without DOX and/or TXR. DOX was injected intraperitoneally at 6 consecutive doses over 12 days (cumulative dose: 12 mg/kg). TXR (150 mg/kg/day; orally) was administered for 4 weeks before DOX challenge. One week after the last injection of DOX, testicular histopathological changes, spermatogenesis activity, and expression of mitochondrial biogenesis genes and miR-140 were determined. Results: DOX challenge significantly increased testicular histopathological changes, decreased testicular expression profiles of sirtuin 1 (SIRT-1) and nuclear respiratory factor-2 (NRF-2), and increased expression of miR-140 (P < 0.05 to P < 0.01). Pretreatment of DOX-received rats with TXR significantly reversed testicular histopathological changes, spermatogenesis activity index, and the expression levels of SIRT-1, peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC-1α), NRF-2, and miR-140 (P < 0.05 to P < 0.01). Conclusion: Reduction of DOX-induced testicular toxicity following TXR pretreatment was associated with upregulation of SIRT-1/PGC-1α/NRF-2 profiles and better regulation of miR-140 expression. It seems that improving microRNA-mitochondrial biogenesis network can play a role in the beneficial effect of TXR on DOX-induced testicular toxicity.

Alpha-lipoic acid preconditioning plus ischemic postconditioning provides additional protection against myocardial reperfusion injury of diabetic rats: modulation of autophagy and mitochondrial function.

BACKGROUND: Investigating the interaction of diabetes with ischemic postconditioning (IPostC)-associated cardioprotection in myocardial ischemia/reperfusion (I/R) damage is of great clinical importance. The present work was designed to determine the possible synergistic effects of alpha-lipoic acid (LA) preconditioning and IPostC on myocardial I/R damage in type-II diabetic rats through modulating autophagy, and the involvement of mitochondrial function. METHODS: High-fat diet/low dose of streptozotocin-induced type-II diabetic model with duration of 12 weeks was used in this study. LA (100 mg/kg/day) was administered orally in diabetic rats for 5 weeks before I/R. Myocardial I/R was established on Langendorff apparatus through the ligation of left anterior descending coronary artery for 35 min, then reperfusion for 60 min. IPostC was carried out immediately at the beginning of the reperfusion. At the end of the experiment, myocardial infarct size (IS), autophagy markers at both gene and protein levels, and mitochondrial ROS production and membrane potential were assessed. RESULTS: Combined conditioning with LA and ischemia significantly decreased the IS of diabetic hearts (P < 0.05), however, single therapies had no significant effects. LA in combination with IPostC more significantly decreased LC3 and p62 mRNA levels (P < 0.01), and LC3II/LC3I and p62 protein levels (P < 0.01). Also, this combined therapy decreased mitochondrial ROS generation and membrane depolarization (P < 0.01). CONCLUSIONS: Pretreatment with LA in diabetic rats notably restored cardioprotection by IPostC via modulating autophagy and restoring mitochondrial function. This combined conditioning might be an effective strategy to diminish I/R damage in diabetic hearts.

The effect of Fumaria parviflora on the expression of sexual hormones along with their receptors in testicles of adult rats induced by varicocele.

Varicocele (VCL) is a pathological dilation of the venous pampiniform plexus of the spermatic cord and is also classified as male factor infertility. The current experiment aimed to examine the protective effect of Fumaria parviflora (FP), as a powerful antioxidant, against reproductive damage induced by VCL. In this experimental study, 32 male rats were randomly allocated into four groups, namely sham (simple laparotomy without additional intervention), FP (healthy rats administered 250 mg/kg FP), VCL + FP (underwent VCL and received 250 mg/kg FP), VCL (underwent VCL without receiving any treatment). The results showed that the number of Sertoli and germ cells were markedly reduced in the VCL group in comparison to the FP-treated and sham groups. The VCl + FP group had significantly higher serum levels of testosterone (T), FSH, and LH hormones than the VCL group. The quality and motility of spermatozoa were reduced in the VCL group compared with other groups (p ≤ 0.05). Moreover, our findings demonstrated that the administration of FP considerably enhanced the mRNA levels of CatSper-1 and -2, SF-1, 3ß-HSD, 17ß-HSD3, LHCGR, and FSHR (p ≤ 0.05). Based on the obtained results, treatment with FP is capable of preventing testicular dysfunction and elevating the concentration of hormones and some crucial genes, such as CatSper1 and 2, SF-1, 3ß-HSD, 17ß-HSD3, LHCGR, and FSHR that contribute to the spermatogenesis process.

Hepatotoxic effects caused by simultaneous exposure to noise and toluene in New Zealand white rabbits: a biochemical and histopathological study.

The aim of this experimental study was to investigate hepatotoxicity effects of noise and toluene, and in particular, to study hepatotoxicity effects of simultaneous exposure to noise and toluene by histopathological and biochemical experiments. To experiment hepatotoxicity effects of noise and toluene, 100 dB white noise and 1000 ppm toluene vapors were generated during two consecutive weeks in healthy male New Zealand White rabbits. Non-simultaneous exposure to noise and toluene increased liver enzymes and the serum levels of superoxide dismutase, malondialdehyde, and total antioxidant capacity, and also decreased serum level of glutathione peroxidase. Alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, malondialdehyde, total antioxidant capacity, and superoxide dismutase levels increased by simultaneous exposure to noise and toluene. Furthermore, catalase and alkaline phosphatase level decreased by simultaneous exposure to noise and toluene. The hematoxylin and eosin stain (H&E) experiments indicated significant swelling, lipidosis, eosinophilic cytoplasm, pyknosis, karyorrhexis, and disruption of the cytoplasmic membrane in the liver tissue due to exposure to noise, toluene and simultaneous exposure to them.

Fumaria parviflora regulates oxidative stress and apoptosis gene expression in the rat model of varicocele induction.

Varicocele is one of the leading causes of male infertility in which oxidative stress induces DNA damages in spermatozoa of patients with varicocele. Recent studies indicated that the treatment with antioxidant agents has protective effects against the formation of reactive oxygen species (ROS). Our research aimed to evaluate the impact of Fumaria Parviflora (FP) on the varicocele-induced testicular injury. For this purpose, 32 adult male Wistar rats (n = 8 per group) were randomly assigned to four groups as follows: sham group, varicocele group, varicocele treatment group and the control treatment group. The experimental groups daily received FP (250 mg/kg) for 8 weeks. The induction of varicocele was conducted by partial occlusion on the left renal vein. The diameter of seminiferous tubules, Johnsen's score and the epithelium thickness improved in the treated-varicocele group as compared to the varicocele group. FP extract could increase the biochemical parameters including superoxide dismutase and glutathione peroxidase, and also decrease malondialdehyde level in the varicocele group. Furthermore, varicocele markedly increased both mRNA and intensity of Bax, while treatment with FP could alleviate them. We concluded that FP could alleviate varicocele, possibly by lowering oxidative stress and testicular damage.

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

Effects of high-intensity interval training on the expression of microRNA-499 and pro- and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats.

BACKGROUND: Because clinical use of doxorubicin (DOX) in chemotherapy is limited due to cardiotoxicity, finding new strategies to alleviate DOX burden and improving patients' health are necessary. Due to positive cardiovascular impacts of high-intensity interval training (HIIT), here we have investigated the effect of HIIT on DOX-induced cardiotoxicity by evaluating the myocardial apoptosis mechanism as well as microRNA-499a-5p expression. METHODS: Male Wistar rats (250-270 g) were randomly allocated into four groups: control, HIIT, DOX, and HIIT+DOX. HIIT was performed as 7 sets of alternative intervals of high and low trainings for 1 h a day, 5 days a week for 6 weeks using a rodent treadmill. After the last session of HIIT, the trained and time-matched control rats received intraperitoneal injection of DOX (20 mg/kg). Three days later, the left ventricular samples were obtained to determine the expression of microRNA and genes and proteins regulating apoptosis via real-time PCR. Myocardial apoptosis was also evaluated using TUNEL staining method. RESULTS: DOX administration significantly increased the expression levels of Bax and caspase-6 mRNAs, Bax protein and Bax/Bcl2 ratio, while reduced the expression levels of Bcl2 mRNA and protein in comparison to control group (P < 0.01). Pre-treatment of DOX-received rats with HIIT significantly up-regulated the Bcl2 and reduced the Bax, Bax/Bcl2, and caspase-6 expression profiles toward control values (P < 0.05), not affecting GSK-3ß expression. In addition, DOX toxicity significantly overexpressed microRNA-499, comparing to control rats (P < 0.01). HIIT significantly reversed this overexpression and also reduced TUNEL-positive apoptotic cells in DOX-received rats (P < 0.05). CONCLUSIONS: The data suggested that prior training of rats with HIIT had protective effect on DOX cardiotoxicity through reversing the expression profiles of pro- and anti-apoptotic factors and microRNA-499 and reducing myocardial apoptosis.

Tetrahydrobenzothiophene carboxamides: Beyond the kinase domain and into the fatty acid realm.

A series of tetrahydrobenzothiophene carboxamides, inspired by structural features present in kinase and SCD1 inhibitors, are presented here. Prototype compound 8 (MMDD13) modulates fatty acid elongase and desaturase indexes, lipid accumulation, while preserving kinase inhibitory activity. This chemotype represents a stepping stone towards chemical probes to study the consequences of lipid metabolism modulation through non-redundant pathways.

How do red and infrared low-level lasers affect folliculogenesis cycle in rat's ovary tissue in comparison with clomiphene under in vivo condition.

Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm2. Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats.

Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus (T2DM), aim of this study was evaluating the influance of regular swimming on serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in high-fat diet-induced diabetic rats. Fourty male Wistar rats were randomly divided into control, diabetic, exercise and diabetic-exercise groups (n = 10). Diabetes was induced by high-fat diet and streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, rats were anestatized and blood samples and pancreatic tissues were collected and used for evaluation of CRP, IL-6, TNF-α and pancreatic histopatholology. Our results showed significantly increase in lymphocytes, monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these parameters significantly reversed to control levels by induction of swimming (p < 0.01). In diabetic group, the levels of CRP, IL-6 and TNF-α increased (p < 0.01), and swimming decreased these factors significantly. Histopathological results of this study also showed that swimming can prevent damage induced by diabetes. The present study indicates that swim training is associated with improved inflammation and inflammatory mediators and pancreatic damage.

Genistein Blunted Detrimental Effects of Polycystic Ovary Syndrome on the Ovarian Tissue of Rats by Improving Follicular Development and Gonadotropin Secretion.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common cause of female infertility worldwide. It has been shown that genistein, a natural isoflavone, may influence follicular competence via the production of gonadotropins in women with PCOS. The current study aims to evaluate the effects of genistein on the ovarian tissue of rats with PCOS. METHODS: Thirty female Wistar rats were randomly divided into the following four groups: Control; PCOS (rats received 2 mg/kbW estradiol valerate); Genistein (rats given 1 mg/kg BW of genistein for 14 days); and Genistein + PCOS. All animals were slaughtered under anesthesia and blood samples were collected for biochemical analysis. Follicular morphology was analyzed based on histologic examination. RESULTS: Histologic examination exhibited enhanced follicular atresia at various stages in the rats with PCOS compared to controls (p<0.001). Induction of PCOS caused significant reduction in gonadotropin levels and steroid hormone levels consistent with insulin resistance (p<0.01). Data showed that 14-day administration of genistein might improve follicular morphology in rats with PCOS (p<0.001). Genistein treatment increased the production of gonadotropins and steroid hormones and alleviated insulin resistance in Rats with PCOS (p<0.001). CONCLUSIONS: This study indicated that genistein treatment exerted a beneficial effect on the ovarian tissue of rats with PCOS by improving follicular growth and hormone balance.

Effect of ghrelin on hypoxia-related cardiac angiogenesis: involvement of miR-210 signalling pathway.

OBJECTIVE: Hypoxia is the main stimulus for angiogenesis. Hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and miR-210 are involved in the hypoxia-induced angiogenesis. This study examined the effects of hypoxia and/or ghrelin on miR-210, HIF-1α, and VEGF levels in the heart of rats. METHODS: Wistar rats were randomly divided into 4 groups (n = 6): control; ghrelin, received daily intraperitoneal injections of ghrelin; hypoxia, was exposed to hypoxic condition; hypoxia + ghrelin, was exposed to hypoxic condition and received intraperitoneal injections of ghrelin, for 2 weeks. Myocardial angiogenesis, the expression level of miR-210, and protein levels of HIF-1α and VEGF were assayed in the heart samples. RESULTS: Hypoxia increased myocardial angiogenesis and cardiac levels of miR-210, HIF-1α, and VEGF. However, ghrelin inhibited these hypoxia-induced changes. Interestingly, ghrelin had no significant effect on miR-210, HIF-1α, and VEGF levels in normoxic condition. CONCLUSION: Ghrelin may be useful as an anti-angiogenic factor.

Swimming training modulates lung injury induced by ovariectomy in diabetic rats: involvement of inflammatory and fibrotic biomarkers.

CONTEXT: Previous studies have noted that the incidence of inflammatory and fibrotic diseases is higher in diabetic menopausal women. OBJECTIVE: In the present study, we evaluated effects of swimming training on inflammatory and fibrotic biomarkers in the lung of ovariectomized diabetic rats. MATERIALS AND METHODS: Forty female rats were assigned into four groups: sham; rats underwent surgery without ovariectomies, OVX: rats that underwent ovariectomies, OVX.Dia: ovariectomized rats with high-fat diet, OVX.Dia. Exe: ovariectomized diabetic rats with 8 weeks of swimming training. At the end of experiment, protein expressions were assessed with western blot. Lung sections were subjected to immunohistochemical and haematoxylin eosin staining. RESULTS: There was a significant difference in the protein expressions between exercise and ovariectomized diabetic groups (p < .05). CONCLUSION: The present study showed strong potential of swimming training on oestrogen deficient diabetic lung. These data encourage further investigation into the inclusive effects of exercise in menopausal diabetic women.

Effects of Different Vitrification Solutions and Protocol on Follicular Ultrastructure and Revascularization of Autografted Mouse Ovarian Tissue.

OBJECTIVE: Many attempts have been made to preserve fertility by improving the cryopreservation of the ovarian tissue. This current studyaimed to improve of direct cover vitrification (DCV) protocol on follicular preservation and angiogenesis in autografted ovarian tissue. MATERIALS AND METHODS: In this experimental study, sixty five female Balb/c mice (5-6 week-old) were anesthetized and their ovaries were dissected. The left ovaries were vitrified by DCV solution, thawed by descending concentrations of sucrose, and then autografted subcutaneously. The right ovaries were autografted with no vitrification procedure prior to transplantation. The animals were sacrificed under anesthesia on the 7th day after transplantation to obtain ovarian tissue. Follicular quality was assessed by histological and ultrastructure observations, and angiogenesis was examined by immunohistochemical staining and real-time polymerase chain reaction (PCR) analysis. RESULTS: The histological and ultrastructure features of the follicles preserved well after vitrification of the ovarian tissue by 10% ethylene glycol (EG) and 10% dimethyl sulfoxide (DMSO). Revascularizationwas manifested prominently in the DCV1-vitrified/grafted ovaries by von Willebrand factor (vWF) and alpha smooth muscle actin (α-SMA) immunostaining. The ovarian tissue vitrified in DCV1 protocol had higher expression levels of angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) 7 days after autotransplantation (P<0.01). CONCLUSION: These findings suggest that DCV with 10% of both EG and DMSO, is an effective cryopreservation solution for preservation of good quality follicles as well an upregulation of angiogenic factors after ovarian tissue transplantation.

Vildagliptin ameliorates renal injury in type 2 diabetic rats by suppressing oxidative stress.

PURPOSE: Vildagliptin has been shown to prevent microvascular complications during diabetes. The aim of this research was to evaluate the antioxidant effects of vildagliptin in diabetic nephropathy. METHODS: The diabetes was induced in the animals by high-fat diet and intraperitoneal injection of 35 mg/kg streptozotocin. After diagnosis of diabetes, the vildagliptin (6 mg/kg/day) was orally administered for one month. The biochemical parameters of blood urea nitrogen, creatinine, insulin, and serum albumin were measured. The levels of stress oxidative markers were detected using spectrophotometry. RESULTS: Treatment with vildagliptin significantly diminished blood glucose, oxidative stress, and reduced creatinine as well as increased insulin secretion. In addition, the vildagliptin improved renal glomerular and tubule interstitial damages and reduced vascular lesions. CONCLUSIONS: The treatment with vildagliptin can be useful in controlling the renal complications of type 2 diabetes mellitus through inhibiting lipid peroxidation and increasing the antioxidant enzymes.

The impacts of garlic and voluntary training alone or together on myocardial miR-126 and miR-210 gene expressions and angiogenesis in healthy rats.

Introduction: microRNAs (miRs) play a critical role in both physiological and pathological processes. Recent studies have shown that garlic and exercise training have many beneficial effects in different disorders including cardiovascular disease. However, their mechanisms have not been fully understood. This study sought to investigate the impact of garlic and voluntary training alone or together on themiR-126 and miR-210 gene expressions and cardiac angiogenesis. Methods: Male Wistar rats were divided into four groups (n=7): (1) Control, (2) Garlic, (3) Exercise, and (4) Garlic+ Exercise. Animals were gavaged with raw fresh garlic homogenate (250 mg/kg body weight/day) or were subjected to voluntary training alone or together for about 6 weeks. The expressions of miR-126 and miR-210 in the heart tissue were measured by real-time PCR and lipid profile in serum was assessed by enzymatic kits. Angiogenesis was determined by immuno staining detection of PECAM-1 and CD31 in the heart tissue. Results: Garlic and exercise up-regulated myocardial miR-126 (P < 0.01), miR-210 (P < 0.001)expressions, and angiogenesis (P < 0.001) which was evidenced by higher CD31 expression. Besides, combination of garlic and exercise amplified their effects on those parameters (P < 0.001). Moreover, both voluntary exercise and garlic alone (P < 0.01) or together (P < 0.001) markedly modulated serum lipid profile. Conclusion: Voluntary exercise and garlic treatment for 6 weeks enhanced myocardial angiogenesis. These alterations were partly due to the increment of miR-126 and miR-210 expressions in the heart tissue in relation to improvement in lipid profile.

Exercise training attenuates diabetes-induced cardiac injury through increasing miR-133a and improving pro-apoptosis/anti-apoptosis balance in ovariectomized rats.

OBJECTIVES: The useful and effective role of exercise program to prevent cardiac tissue apoptosis and fibrosis in ovariectomized type 2 diabetic (T2DM) rats (OVR.D) is well known. The current study aimed to investigate the simultaneous effects of T2DM and swimming plan on the expression of some apoptotic, anti-apoptotic biomarkers and glycogen changes in the cardiac muscle tissue of ovariectomized (OVR) rats. MATERIALS AND METHODS: Forty rats were randomly sorted into 4 equal categories; sham, OVR, OVR.D and diabetic ovariectomized with an 8 week of swimming plan (OVR.D.E). Lipid profile and miR-133, Bcl-2, Bax, caspase-3 and caspase-8 levels were evaluated in the cardiac tissue. RESULTS: Ovariectomy significantly (P-value<0.05) increased cholesterol, triglyceride, LDL, Bax, caspase-3, caspase-8 and decreased (P-value<0.05) HDL, miR-133, Bcl-2 in the cardiac tissue and a further reduction in the expression of miR-133, Bcl-2 and an enhancement in Bax, caspase-3 and caspase-8 in OVR.D rats was observed (P-value<0.01). However, exercise training significantly reversed all the measured parameters (P-value<0.05). Also, exercise training improved abnormal tissue structure, fragmentation and irregular form of glycogen granules in the OVR.D.E compared to OVR and OVR.D animals. CONCLUSION: Exercise training could prevent the cardiac disturbance, enhance the expression of anti-apoptotic markers and decrease apoptotic biomarkers in the hearts of OVR.D animals. Therefore, based on the findings of this study suggested using the exercise's beneficial effects for prevention of the cardiac cell death in OVR.D animals.

Swimming training attenuates pancreatic apoptosis through miR-34a/Sirtu in1/P53 Axis in high-fat diet and Streptozotocin-induced Type-2 diabetic rats.

OBJECTIVE: The present study sought to evaluate the miR-34a/Sirtuin1/p53 pro-apoptotic pathway, and reveal its modulation in diabetic rats undergoing swimming exercise. METHODS: Twenty-eight male Wistar rats were divided into four groups. They were inducted to develop diabetes by injection of streptozotocin. After 12 weeks of swimming, the pancreatic tissue of these rats were removed to be evaluated for the expression level of Sitruin1/P53/miR-34a through qPCR. RESULTS: Findings indicated a marked rise in the expression of miR-34 and P53 (P < 0.01) as well as a significant decrease in expression of Sitruin1 (P < 0.01) in the diabetic group. In contrast, swimming resulted in a significant decrease in miR-34a expression (P < 0.01), and a prominent rise in the level of Sitruin1 in the swimming-trained-diabetic group (P < 0.01). Additionally, high, moderate and low apoptosis rate were observed in the pancreatic tissue of the diabetic, swimming-trained diabetic, and control groups, respectively. CONCLUSION: Our findings suggested a correlation between pancreatic tissue apoptosis rate and miR-34a/Sitruin1/p53 signaling, that was subject to modulation by training.

Preparation and characterization of novel anti-inflammatory biological agents based on piroxicam-loaded poly-ε-caprolactone nano-particles for sustained NSAID delivery.

Piroxicam (PX), a main member of non-steroidal anti-inflammatory drugs (NSAIDs), is mainly used orally, which causes side effects of the gastrointestinal tract. It also has systemic effects when administered intramuscularly. Intra-articular (IA) delivery and encapsulation of PX in biodegradable poly-ε-caprolactone (PCL) nanoparticles (NPs) offer potential advantages over conventional oral delivery. The purpose of this study is the development of a new type of anti-inflammatory bio-agents containing collagen and PX-loaded NPs, as an example for an oral formulation replacement, for the prolonged release of PX. In this study, the PX was encapsulated in PCL NPs (size 102.7 ± 19.37 nm, encapsulation efficiency 92.83 ± 0.4410) by oil-in-water (o/w) emulsion solvent evaporation method. Nanoparticles were then characterized for entrapment efficiency, percent yield, particle size analysis, morphological characteristics, and in vitro drug release profiles. Eventually, the NPs synthesized with collagen were conjugated so that the NPs were trapped in the collagen sponges using a cross-linker. Finally, biocompatibility tests showed that the anti-inflammatory agents made in this study had no toxic effect on the cells. Based on the results, it appears that PX-loaded PCL NPs along with collagen (PPCLnp-Coll) can be promising for IA administration based on particulate drug delivery for the treatment of arthritis.