Long-Term Exposure of Lead Acetate on Rabbit Renal Tissue.

BACKGROUND: Lead has been widely used in different industries for ages. It is one of the heavy metals, highly poisonous even at low doses, and has biochemical, physiological and behavioral side effects on human and animals. It has been shown that lead has toxic effects on different tissues such as neural and genitourinary tissues, cardiovascular systems and blood. Therefore, high attention has been paid to its environmental pollutions. OBJECTIVES: Although many histological and biochemical studies have reported about the effects of lead on the renal tissue, there are a few studies about the ultrastructure and morphometric effects of lead on the kidney. Hence, the aim of this study was the evaluation of morphology and morphometrics of rabbit renal urinary barrier ultrastructure following long-term exposure to lead acetate. MATERIALS AND METHODS: In this experimental study, 20 male New Zealand rabbits were divided into control and test groups (10 in each). The test group was injected intraperitoneally with chronic dose (8.5 mg/kg of body weight) of lead acetate and for the control group the same volume of normal saline was used, every other day for 10 weeks. After anesthetizing, the biopsies of renal tissues were taken for light and electron microscopic morphometric and morphologic analyses. RESULTS: Long-term exposure to lead acetate caused histopathology effects including dilatation, congestion, nuclei heterochromatic effects, increase in diameter of renal tubules and urinary barrier thickness in rabbit renal tissue. CONCLUSIONS: Quantitative and qualitative results of long-term lead acetate exposure showed many histopathology side-effects, especially in the urinary barrier.

Efficacy of Compound Therapy by Ginseng and Ciprofloxacin on Bacterial Prostatitis.

OBJECTIVE: Genitourinary tract infections play a significant role in male infertility. Infections of reproductive sex glands, such as the prostate, impair function and indirectly affect male fertility. The general aim of this study is to investigate the protective effect of Korean red ginseng (KRG) on prostatitis in male rats treated with ciprofloxacin (CIPX). MATERIALS AND METHODS: In this experimental study, we randomly divided 72 two male Wistar rats into 9 groups. The groups were treated as follows for 10 days: i. Control (no medication), ii. Sham [(normal saline injection into the vas deferens and oral administration of phosphate-buffered saline (PBS)], iii. Ginseng, iv. CPIX, v. CIPX+ginseng, vi. Uropathogenic Escherichia coli (E. coli) (UPEC), vii. UPEC+ginseng, viii. UPEC+CIPX, and ix. UPEC+ginseng+CIPX. The rats were killed 14 days after the last injection and the prostate glands were removed. After sample preparation, routine histology was performed using hematoxylin and eosin staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) method was used to determine the presence of apoptotic cells. RESULTS: The severity score for acinar changes and inflammatory cell infiltration in the UPEC+CIPX group did not significantly different from the UPEC group. However this score significantly decreased in the UPEC+CIPX+ginseng group compared to the UPEC group. Apoptotic index of all ginseng treated groups significantly decreased compared to the UPEC and CPIX groups. CONCLUSION: These results suggested that ginseng might be an effective adjunct in CIPX treatment of prostatitis. The combined use ginseng and CIPX was more effective than ginseng or CIPX alone.

Rosiglitazone, but not epigallocatechin-3-gallate, attenuates the decrease in PGC-1α protein levels in palmitate-induced insulin-resistant C2C12 cells.

Alteration of lipid metabolism is an important mechanism for the treatment of insulin resistance. PGC-1α, a key regulator of mitochondrial biogenesis and function, plays an important role in the improvement of insulin sensitivity by increasing fatty acids ß-oxidation. In the present study, the effects of epigallocatechin-3-gallate (EGCG), an anti-obesity agent and enhancer of lipid catabolism, on PGC-1α protein expression was examined and compared with anti-diabetic drug rosiglitazone (RGZ). After differentiation of C2C12 myoblasts to myotubes, insulin resistance was induced by palmitate treatment. Then the expression of the PGC-1a gene and glucose uptake were evaluated before and after treatment with RGZ and EGCG. Palmitate treatment significantly decreased PGC-1α protein expression in C2C12 cells (P < 0.05). RGZ could restore the expression of PGC-1α in palmitate treated cells (P > 0.05), while EGCG had no significant effect on the expression of this gene (P < 0.05). RGZ and EGCG significantly improved glucose uptake (by 2- and 1.54-fold, respectively) in myotubes treated with palmitate. These data suggest that RGZ and EGCG both exert their anti-diabetic activity by increasing insulin sensitivity, but with different molecular mechanisms. This effect of RGZ, unlike EGCG, is mediated, at least partly, by increasing PGC-1α protein expression.

Tissue engineered scaffolds in regenerative medicine.

Stem cells are self-renewing cells that can be differentiated into other cell types. Conventional in vitro models for studying stem cells differentiation are usually preformed in two-dimensional (2D) cultures. The design of three-dimensional (3D) in vitro models which ideally are supposed to mimic the in vivo stem cells microenvironment is potentially useful for inducing stem cell derived tissue formation. Biodegradable scaffolds play an important role in creating a 3D environment to induce tissue formation. The application of scaffolding materials together with stem cell technologies are believed to hold enormous potential for tissue regeneration. In this review, we provide an overview of application of tissue engineered scaffolds and stem cells for the development of stem cell-based engineered tissue replacements. In particular, we focus on bone marrow stem cells (BMSCs) and mesenchymal stem cell (MSCs) due to their extensive clinical applications.

Curcumin prevents the structural changes induced in the rats' deep cerebellar nuclei by sodium metabisulfite, a preservative agent.

OBJECTIVE: To evaluate the the possible neurotoxic effects of sulfite and the protective potential of curcumin on the deep cerebellar nuclei using stereological methods. METHODS: The rats were randomly divided into five experimental groups (n=6): Group I: distilled water, Group II: Olive oil, Group III: Curcumin (100 mg/kg/day), Group IV: Sodium metabisulfite (25 mg/kg/day), and Group V: Sodium metabisulfite+curcumin. At the end of 56 d, the right cerebellar hemispheres were removed and assigned to stereological studies. The total volume and total neuron number of deep cerebellar nuclei were assessed using Cavalieri and optical disector methods, respectively. RESULTS: The data showed ∼20% and ∼16% decrease was respectively observed in the total volume and the total neuron number of the deep cerebellar nuclei of the sulfite-treated rats in comparison to the distilled water group (P<0.04). However, no significant change was observed in the total volume and neuronal number of the deep cerebellar nuclei in sulfite+curcumin-treated rats and curcumin played a protective role against sulfite. Curcumin or its vehicle (olive oil) did not induce any significant changes. CONCLUSIONS: Curcumin, the main part of the turmeric, could prevent the structural changes induced in the deep cerebellar nuclei by sodium metabisulfite, a preservative agent, in rats.

Increased expression of transforming growth factor-ß and receptors in primary human airway fibroblasts from chemical inhalation patients.

The widespread use of sulfur mustard (SM) as a chemical warfare agent in the past century has proved its long-lasting toxic effects. Despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Transforming growth factor (TGF-ß), a cytokine that affects many different cell processes, has an important role in the lungs of patients with some of chronic airway diseases, especially with respect to airway remodeling in mustard lung. Primary airway fibroblasts from epibronchial biopsies were cultured, and gene expression of TGF-ß1, TGF-ß2, TbR-I and TbR-II in fibroblasts of SM injured patients and controls were investigated. Expression of TGF-ßs and receptors was measured by RT-PCR. Protein level of TGF-ß1 was surveyed by western blot. Our findings revealed that expression levels of TGF-ß1, TGF-ß2, TbR-I and TbR-II were upregulated in the airway fibroblasts of SM exposed patients in comparison with control samples. TGF-ß1 expression was shown to be markedly increased in primary lung fibroblasts of chemically injured patients. Our novel data, suggested that over-expression of TGF-ß molecule and receptors in primary airway fibroblasts of mustard gas injured patients may be involved in progression of airway remodeling of these patients.

siRNA therapeutics in the treatment of diseases.

siRNAs are a class of dsRNAs, 21-23 nucleotides in length, which are able to silence their target genes through enzymatic cleavage of target mRNA. The sequence-specific gene-silencing by siRNA can be used as a new therapeutic approach for treatment of a variety of diseases that are incurable by conventional drugs. Many efforts have been made to overcome the problems related to delivery, stability, off-target gene silencing and immunostimulatory effects of siRNA. Different studies have carried out done to improve in vitro and in vivo delivery of naked or formulated siRNAs. In this review, different aspects of using siRNA as a new class of drugs will be discussed.

Maternal Nicotine Induces Collagen Type IV Changes in the Mice Lung Parenchyma and its Vessels.

BACKGROUND: One of the undesirable effects of maternal nicotine exposure during pregnancy is pulmonary hypertension. Since nicotine binds to its receptors on pulmonary vessels the hypothesis of this research was the possible structural changes that nicotine may cause on newborn vessels. MATERIALS AND METHODS: Twenty-four female BALB/c mice were mated and finding vaginal plug was assumed as day zero of pregnancy. Pregnant mice were divided into 2 experimental and 2 control groups. Experimental group 1 received 3 mg/kg nicotine intraperitoneally from day 5 of gestation until the last day of pregnancy. Experimental group 2 received the same amount of nicotine during the same gestational days as well as the first 2 weeks after birth (lactation). The control groups received the same volume of normal saline during the same periods. At the end of exposure times, all the newborns (experimental and control) were anesthetized, their lungs were removed and immunohistochemical studies were carried out for tracing collagen. RESULTS: Our findings indicated that collagen reaction in the bronchial basement membrane (BBM) and extracellular matrix (ECM) of the lung parenchyma in experimental groups increased significantly compared to the control groups but these changes were not observed in BM of lung vessels in the experimental groups. CONCLUSION: These data indicate that nicotine exposure during pregnancy does not cause a significant change in collagen type IV in BM of lung vessels. But this does not mean that other types of collagen fibers do not indicate change because the wall thickness of pulmonary vessels in experimental groups increased significantly compared to the control groups.

Inductive role of collagen type IV during nephrogenesis in mice.

INTRODUCTION: During nephrogenesis, transition of mesenchyme to the epithelium of tubules and glomeruli occurs via the interaction of ureteral bud and metanephric mesenchyme. The distribution pattern of collagen type IV suggests that a regulated balance of activities is required to facilitate migration of the ureteral bud branches into the mesenchyme and to control early extracellular matrix changes during tubulogenesis. We used a specific antibody for tracing collagen type IV basement membrane during renal tubules morphogenesis. MATERIALS AND METHODS: Twenty female Balb/C mice were divided randomly into 10 groups and were kept until finding vaginal plug was as an indicator of day zero of pregnancy. Twelve pregnant mice were sacrified by cervical dislocation in one of gestational days 13 to 18 and their fetuses were fixed, serially sectioned, and underwent immunohistochemical study for tracing of collagen type IV in basement membrane of glomeruli. The same processes were used for kidneys preparation on postnatal days 5, 10, 15, and 20 in newborns of 2 mothers for each day. RESULTS: Collagen type IV showed weak reaction on day 14 of gestation in tubular basement membrane. The amount of collagen increased continuously until the following days of fetal life and of the first 5 postnatal days in basement membrane. After this period, collagen type IV reaction was not showed significant change in newborns. CONCLUSION: These results indicate that developmental changes in various nephron segments from most immature stages to most differentiated structures are dependent on the collagen type IV expression.