scholarly journals Is ferroptosis involved in ROS-induced testicular lesions in a varicocele rat model?

2021 ◽  
Vol 31 (1) ◽  
Author(s):  
Erfaneh Shaygannia ◽  
Mohammad H. Nasr-Esfahani ◽  
Fattah Sotoodehnejadnematalahi ◽  
Kazem Parivar

Abstract Background Ferroptosis is an iron-dependent cell death that is distinct from apoptosis. Based on excessive amounts of iron and reactive oxygen species in varicocele (VCL) rats, we hypothesize that ferroptosis might be involved in VCL. In addition, since alpha-lipoic acid (ALA) was shown to have both antioxidant and anti-ferroptotic activity we assessed in the present work the status of ferroptosis in our varicocele model and the protective effect of ALA. To this end, 70 male Wistar rats were divided into 7 groups: control, sham and varicocele groups which were initially sacrificed 2 months after the operation to verify the induction of varicocele. A second batch of the same 3 groups were sacrificed 4 months after varicocele induction to evaluate the effect of ALA supplementation. The parameters measured were chromatin integrity (aniline blue and acridine orange staining), lipid peroxidation (BODIPY staining), testicular morphometry and iron content. In addition, redox (GSH and NADPH) and ferroptosis (Nrf2, Slc7a11, P53 and p-Jnk) markers were evaluated at 2 and 4 months post-operation. Result The alteration of the spermatic parameters made it possible to verify the induction of the varicocele. Iron accumulated well in the testicles during varicocele and decreased significantly following ALA treatment. Ferroptotic molecular markers at the mRNA and protein levels were not significantly altered. ALA supplementation did not alter NADPH values, but increased GSH levels. Conclusion Despite the increased accumulation of iron in the testes 2 and 4 months after surgical induction of varicocele, molecular evidence did not demonstrate the involvement of ferroptosis. This could be explained by the mosaic nature of the varicocele affecting some seminiferous tubules and not others which could mask variations in molecular markers. In parallel, our study confirms that ALA stimulates the NRF2 pathway.

2017 ◽  
Vol 68 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Mahmoud M. Said ◽  
Marwa M. Abd Rabo

AbstractAluminium (Al) is a neurotoxic metal that contributes to the progression of several neurodegenerative diseases. The aim of the present study was to evaluate the protective effect of dietary eugenol supplementation against aluminium (Al)- induced cerebral damage in rats. Male Wistar rats were divided into four groups: normal controls, rats fed a diet containing 6,000 μg g-1eugenol, rats intoxicated daily with aluminium chloride (84 mg kg-1body weight) p. o. and fed either a basal diet or a eugenol-containing diet. Daily oral administration of Al for four consecutive weeks to rats significantly reduced brain total antioxidant status (TAS) (11.42±0.31 μmol g-1tissue, p<0.001) with a subsequent significant enhancement of lipid peroxidation (MDA) (32.55±1.68 nmol g-1tissue, p<0.002). In addition, Al enhanced brain acetylcholinesterase activity (AChE) (46.22±4.90 U mg-1protein, p<0.001), tumour necrosis factor alpha (TNF-α) (118.72±11.32 pg mg-1protein, p<0.001), and caspase 3 (Casp-3) (8.77±1.26 ng mg-1protein, p<0.001) levels, and in contrast significantly suppressed brain-derived neurotrophic factor (BDNF) (82.74±14.53 pg mg-1protein, p<0.002) and serotonin (5-HT) (1.54±0.12 ng mg-1tissue, p<0.01) levels. Furthermore, decreased glial fibrillary acidic protein (GFAP) immunostaining was noticed in the striatum of Al-intoxicated rats, compared with untreated controls. On the other hand, co-administration of dietary eugenol with Al intoxication restored brain BDNF (108.76±2.64 pg mg-1protein) and 5-HT (2.13±0.27 ng mg-1tissue) to normal levels, enhanced brain TAS (13.43±0.24 μmol g-1tissue, p<0.05), with a concomitant significant reduction in TNF-α (69.98±4.74 pg mg-1protein) and Casp-3 (3.80±0.37 ng mg-1protein) levels (p<0.001), as well as AChE activity (24.50±3.25 U mg-1protein, p<0.001), and increased striatal GFAP immunoreactivity, compared with Al-treated rats. Histological findings of brain tissues verified biochemical data. In conclusion, eugenol holds potential as a neuroprotective agent through its hydrophobic, antioxidant, and anti-apoptotic properties, as well as its neurotrophic ability against Al-induced brain toxicity in rats.


2012 ◽  
Vol 120 (02) ◽  
pp. 84-88 ◽  
Author(s):  
S. Chen ◽  
X. Zhuang ◽  
Y. Liu ◽  
A. Sun ◽  
C. Chen

AbstractLipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.


2014 ◽  
Vol 31 (02) ◽  
pp. 075-081
Author(s):  
A. Akinlolu ◽  
O. Akinola ◽  
P. Khobe ◽  
K. Obasi ◽  
O. Dada

Abstract Introduction: AAzathioprine and Methotrexate are both used in the treatment of cancer; and are classified as cytotoxic drugs with reported adverse effects such as oxidative damage to the DNA/RNA, the testes and sperm cells. This study, therefore, tested the hypothesis that AAzathioprine and Methotrexate administrations impair the morphology and functions of the testes in adult male wistar rats. Methods: AAzathioprine (50-150mg per day) and Methotrexate (2.5mg per week) are used in the treatment of cancer in adult Man. We tested the hypothesis that AAzathioprine and Methotrexate impair the morphology and functions of testes in rats. Forty adult male wistar rats (150-230g) were employed in the study: Control Group I received physiological saline while Experimental Groups II - V received oral administrations of 5mg/kg/bodyweight of AAzathioprine per day, 15mg/kg/bodyweight of AAzathioprine per day, 8mg/kg/bodyweight of Methotrexate per week and 20mg/kg/bodyweight of Methotrexate per week respectively for 35 days. Results: Histological examinations of the testes of rats of Groups II - V showed dose-dependent morphological anomalies such as fewer collagen ibers of connective tissues, disrupted seminiferous tubules and scanty spermatozoa when compared to rats of Group I. Statistical analyses showed dose-dependent elevated levels (P≤0.05) of superoxide dismutase and malondialdehyde in testes homogenates of rats of Groups II - V when compared to rats of Group I. This implied increased oxidative stress in rats of Groups II - V. Evaluations of Follicle Stimulating Hormone and Testosterone showed dose-dependent significantly elevated levels (P≤0.05) in rats of Groups II - V when compared to rats of Group I. Conclusions: Our findings are consistent with the stated hypothesis.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1350 ◽  
Author(s):  
Anna Signorile ◽  
Domenico De Rasmo ◽  
Antonella Cormio ◽  
Clara Musicco ◽  
Roberta Rossi ◽  
...  

Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student’s t-test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins.


2017 ◽  
Vol 95 (8) ◽  
pp. 969-976 ◽  
Author(s):  
Martina Muráriková ◽  
Miroslav Ferko ◽  
Iveta Waczulíková ◽  
Magdaléna Jašová ◽  
Ivana Kancirová ◽  
...  

Diabetes mellitus, besides having deleterious effects, induces cardiac adaptation that may reduce the heart’s susceptibility to ischemia–reperfusion (IR) injury. This study aimed to investigate whether changes in mitochondrial properties are involved in the mechanisms of increased resistance of the diabetic heart to IR. Adult male Wistar rats were made diabetic by a single dose of streptozotocin (65 mg·kg–1, i.p.), and on the day 8, Langendorff-perfused hearts were subjected to 30 min global ischemia and 40 min reperfusion. Baseline preischemic parameters in the diabetic hearts did not differ markedly from those in the nondiabetic controls, except for lower left ventricular developed pressure, higher mitochondrial membrane fluidity, and protein levels of manganese superoxide dismutase. On the other hand, diabetic hearts showed significantly better post-IR functional restoration and reduced arrhythmogenesis associated with lower reactive oxygen species production as compared with healthy controls. IR decreased membrane fluidity in both experimental groups; however, it led to a complete recovery of mitochondrial Mg2+-ATPase activity in diabetics in contrast to its reduction in nondiabetics. These findings indicate that the heart may become adapted to diabetes-induced alterations that might increase its tolerance to an ischemic insult. Preserved mitochondrial function might play a role in the mechanisms of the heart’s resistance to IR injury in diabetics.


Dose-Response ◽  
2017 ◽  
Vol 15 (4) ◽  
pp. 155932581772926 ◽  
Author(s):  
Mosunmola Busayo Omotola ◽  
Isaac O. Adeosun ◽  
Efere M. Obuotor ◽  
Rufus O. Akomolafe ◽  
Olugbenga A. Ayannuga

This study evaluated the ameliorative and prophylactic effects of 2 different doses of polyphenolic-rich fraction of Garcinia kola (PPRF Gk) seeds on the histology and hormones of pituitary–testicular axis of male Wistar rats. Thirty-five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each. Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by propylene glycol (0.2 mL/d) and 600 mg/kg of PPRF Gk, respectively, for 21 days. Group III received sodium arsenate (8 days), left untreated for 21 days. Groups IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRF Gk (300 and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRF Gk (300 and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg) for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose and their blood collected through cardiac puncture. Blood sera were assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone using immunoassay techniques. Histology of the pituitary gland and testes was carried out. A significant reduction was observed in the concentration of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The concentrations of both LH and testosterone showed significant decreases in groups IV, V, VI, and VII in comparison with group I. Group III presented with the lowest serum hormonal concentrations. Photomicrographs of the pituitary gland revealed greatly reduced basophils in group III and mildly reduced basophils in groups IV, VI, and VII in comparison with groups I and II. Group V revealed hypercellularized and distorted basophils. Photomicrographs of the testes showed detachment of the seminiferous tubules from the basement membrane and disruption of the interstitial space which was worse in group III, moderate in groups V and VI, and mild in group VII. In conclusion, PPRF Gk effected a dose-dependent reversal and prevention of the perturbations caused by arsenate in rats.


Phytotaxa ◽  
2018 ◽  
Vol 360 (3) ◽  
pp. 220 ◽  
Author(s):  
ZAHRA ARABI ◽  
FARROKH GHAHREMANINEJAD ◽  
RICHARD K. RABELER ◽  
IRINA SOKOLOVA ◽  
GÜNTHER HEUBL ◽  
...  

The status of the genus Dichodon has long been debated, and its taxonomic position in tribe Alsineae has been changed during the time from a section or subgenus in Cerastium to genus sister to Holosteum. This group comprises important members of wet meadows in alpine and subalpine vegetation of Europe, arctic regions, and SW-Asia plus one species known as a weed in N-America, and a further one occuring in mountains of Taiwan. In order to clarify the taxonomic questions concerning this group and its species delimitation, we constructed phylogenetic trees, selecting several species belonging to tribe Alsineae as representatives of major lineages of this tribe as well as several accessions of Dichodon. Morphological studies focused more intensively on members of Dichodon using herbarium specimens and direct field examinations. The results confirm those of recent molecular phylogenetic studies, indicating Dichodon as a monophyletic genus sister to Holosteum and not Cerastium. In addition, the obtained cladograms support five distinct groups in Dichodon corresponding to five species of this genus we recognize in Iran, the focal area of this study. Seed micromorphology provides strong support for the recognition of Dichodon as a separate genus, but it is not informative at species and subspecies ranks due to constancy of most of seed characters within the genus. As part of this study, a new species—Dichodon alborzensis—is described, D. kotschyi is reported in Iran for the first time, and Cerastium schischkinii is placed in synonymy (new synonymy) under D. kotschyi.


Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2550-2556
Author(s):  
Christian H. Ottensmeier ◽  
Freda K. Stevenson

Primary diffuse large B-cell lymphomas (DLBCLs) are aggressive tumors accounting for approximately 40% of B-cell malignancies. The immunoglobulin (Ig) variable region genes have undergone rearrangement and are commonly somatically mutated. The majority show intraclonal variation which indicates that somatic mutation has continued after transformation. Typically, cells of DLBCLs express Ig of a single isotype, but there may be accompanying cells that express alternative isotypes. To probe the status of the isotype switch process in DLBCL, 4 cases of tumor-derived constant region transcripts of all isotypes were investigated. Following the identification of the VDJ sequences, the presence of the major isotype expected from immunohistochemical analysis was confirmed at the RNA level. Another 3-4 alternative isotypes were revealed in all cases, some of which could also be detected by immunohistochemistry. All cases were somatically mutated with an intraclonal variation. In 2 cases there were clearly distinct patterns of somatic mutation between isotypes, which was consistent with independent evolution of the tumor subpopulations. There was apparent clustering of mutational patterns into either an IgMD/IgG3/IgA set or an IgG1/IgA set, indicating that the switch to IgA can occur by different routes. Alternative isotype expression is evident in DLBCL at both the RNA and protein levels. The pattern of mutation indicates that switching is occurring in subpopulations of the tumor after malignant transformation. The findings support the concept that isotype switch events may be a feature of DLBCL.


Zootaxa ◽  
2009 ◽  
Vol 2173 (1) ◽  
pp. 66-68 ◽  
Author(s):  
FELIPE F. CURCIO ◽  
VÍTOR DE Q. PIACENTINI ◽  
DANIEL S. FERNANDES

The genus Erythrolamprus Boie (1826) comprises six species of Central and South American false coral snakes (Peters & Orejas-Miranda 1970; Zaher 1999; Curcio et al. 2009). It is traditionally allocated in the tribe Xenodontini (subfamily Xenodontinae), along with the genera Liophis, Lystrophis, Umbrivaga, Waglerophis and Xenodon (sensu Dixon 1980; Cadle 1984; Myers 1986; Ferrarezzi 1994; Zaher 1999). Although Xenodontini is supported by morphological and molecular evidence, phylogenetic relationships and classification within the tribe have been the subject of recent debate. Molecular phylogenetic studies have recovered clades with Erythrolamprus nested within some representatives of the genus Liophis (Vidal et al. 2000; Zaher et al. 2009), partly corroborating previous hypotheses based on morphology (e.g. Dixon 1980).


Sign in / Sign up

Export Citation Format

Share Document