Protective effect of melatonin against methotrexate-induced testicular damage in the rat model: An experimental study

Background: Methotrexate (MTX) has been shown to affect the testes adversely, especially the seminiferous epithelium. As melatonin, an endocrine hormone, has been shown to normalize testicular function, its ability to prevent MTX-induced testicular damage should be considered. Objective: Based on the antioxidant, anti-inflammatory, and antiapoptotic activities of melatonin, this study aimed to investigate its protective effect against testicular damage induced by MTX. Materials and Methods: Forty adult male rats (200-230 g) were divided into five groups (n = 8/each). The rats in group I were injected with vehicle as a control. In group II, the rats were received intraperitoneal injections of melatonin (8 mg/kg) for 15 consecutive days. The rats in group III were intravenously injected with MTX (75 mg/kg) for 15 consecutive days. The remaining two groups received melatonin (8 mg/kgBW) for 15 (group IV) and 30 (group V) consecutive days, intraperitoneally, and then intravenously received MTX (75 mg/kgBW) on days 8 and 15 of the experimental period. Reproductive parameters, including epididymal sperm concentration, testicular tyrosine-phosphorylated protein expression, steroidogenic acute regulatory (StAR) protein expression, and caspase-3 and malondialdehyde levels, were examined. Results: The sperm concentrations (×106/ml) of groups IV (58.75 ± 1.28) and V (55.93 ± 2.57) were improved significantly (p = 0.032) compared with that of group II (32.92 ± 2.14). The seminiferous epithelium in groups IV and V also increased, while caspase- 3 expression decreased. In the melatonin-treated groups, the expression of tyrosinephosphorylated proteins at 32 kDa was decreased and that of proteins at 47 kDa was increased compared with the MTX group. StAR protein expression was not altered in any of the groups. Conclusion: Our results indicate that melatonin improves the epididymal sperm concentration by decreasing the expression of caspase-3 and increasing that of tyrosine-phosphorylated proteins in MTX-treated testes. Key words: Melatonin, Testis, Sperm, Methotrexate, Caspase-3, Tyrosine phosphorylation.

Download Full-text

The expression and role of β3AR protein in myocardial ischemia/reperfusion in rats

Archives of Medical Science ◽

10.5114/aoms/135884 ◽

2021 ◽

Author(s):

Zi-Long Wang ◽

Xiao-Chen Sun ◽

Rong Luo ◽

Dong-Ye Li ◽

Hao-Chen Xuan

Keyword(s):

Myocardial Ischemia ◽

Protein Expression ◽

Caspase 3 ◽

Sham Group ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Sd Rats ◽

Group I ◽

Myocardial Ischemia Reperfusion

IntroductionTo explore serum norepinephrine (NE) concentration and β3-adrenoceptor (β3AR) protein expression at different times during myocardial ischemia/reperfusion (I/R) and examine the role of β3AR in I/R.Material and methods28 Sprague-Dawley (SD) rats were randomly divided into one sham group and six I/R groups. The rats in the I/R groups were subjected to ischemia for 45 minutes. After reperfusion, the serum NE concentration and the β3AR protein expression in the myocardial tissue of the left ventricular injury region were detected. Another 18 SD rats were randomly divided into a sham group, I/R groups, and I/R + BRL37344 group.ResultsCompared with the sham group, the serum NE concentration of rats in the I/R groups significantly increased at 6 hours (P < 0.001). The serum NE concentration and myocardial β3AR protein expression were both highest at 72 hours. Compared with the sham group, the expressions of the pro-apoptotic proteins Bax and cleaved caspase-3 after I/R were significantly increased (P < 0.01, P < 0.001, respectively), and the expression of anti-apoptotic protein Bcl-2 was significantly decreased (P < 0.01). Compared with I/R groups, the expressions of Bax and cleaved caspase-3 in the I/R + BRL37344 group were significantly decreased (P < 0.05, P < 0.01, respectively).ConclusionsWith the prolongation of myocardial I/R in rats, serum NE concentration and β3AR protein expression showed a significant increase trend and reached a peak at 72 hours. Specific β3AR agonist BRL37344 can reduce myocardial I/R injury in vivo in rats, alleviate apoptosis, reduce infarct size, and improve cardiac function.

Download Full-text

A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000300015 ◽

2015 ◽

Vol 51 (3) ◽

pp. 637-642 ◽

Cited By ~ 6

Author(s):

Seyyed Ali Mard ◽

Zahra Nikraftar ◽

Yaghoob Farbood ◽

Esrafil Mansouri

Keyword(s):

Gastric Mucosa ◽

Protein Expression ◽

Protective Effect ◽

Caspase 3 ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Celiac Artery ◽

Male Rats ◽

Gastric Mucosal Lesions ◽

Inflammatory Protein

The aim of the present study was to investigate the protective effect of crocin on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rats. Thirty-two male rats were randomly divided into sham, I/R, I/R + crocin pretreatment and crocin alone groups. To induce I/R lesions, the celiac artery was clamped for 30 min, and the clamp was then removed to allow reperfusion for 3 h. Crocin-pretreated rats received crocin (15 mg/kg, i.p.) 30 min prior to the induction of I/R injury. Samples of gastric mucosa were collected to quantify the protein expression of caspase-3, an apoptotic factor, and inducible nitric oxide synthase (iNOS), a pro-inflammatory protein, by Western blot. Pretreatment with crocin decreased the total area of gastric lesions and decreased the protein expression levels of caspase-3 and iNOS induced by I/R injury. Our findings showed a protective effect of crocin in gastric mucosa against I/R injury. This effect of crocin was mainly mediated by reducing the protein expression of iNOS and caspase-3.

Download Full-text

42 SEMEN FERTILITY OF THE BULL EVALUATED BY SECOND-ORDER STATISTICS

Reproduction Fertility and Development ◽

10.1071/rdv22n1ab42 ◽

2010 ◽

Vol 22 (1) ◽

pp. 178

Author(s):

T. F. Silva ◽

J. B. Barreto Filho ◽

R. S. Macedo ◽

M. V. C. Ferraz Jr ◽

R. A. Braga Jr ◽

...

Keyword(s):

Order Statistics ◽

Pearson Correlation ◽

Sperm Concentration ◽

Second Order ◽

Semen Parameters ◽

Ultrasound Images ◽

Second Order Statistics ◽

Group I ◽

Frozen Semen ◽

Group Ii

The biospeckle (BSL) is based on the incidence of laser light upon active biological materials, followed by analysis and manipulation of secondary images, and then, application to those images of a second-order statistics technique called the inertial moment (IM) that results in information about the activity of the specimen. This technique was previously used to analyze sperm motility. A bull’s fertility could be evaluated by several semen parameters in vitro and more precisely by conception rates of AI heifers. The objective of this work was to evaluate the fertility of bull’s frozen semen showing different levels of activity in an AI program. Semen of 6 mature IA donor bulls (Bos taurus indicus) was previously divided in 2 groups (group I: motility ≥50%; group II: motility <50%), each group comprising 3 animals. Sperm concentration was 30 to 35 × 106 cells per straw. Semen was thawed at 37°C for 30 s in a water bath. Samples were illuminated by nonpolarized He-Ne laser (632 nm, 10 mW) for 40 s, the time needed to take 512 images under a time rate of 0.08 s. Images were acquired by a CCD camera and analyses were conducted by building space-time speckle matrices from center columns of 512 images of the dynamic speckle and then the IM was calculated. Beef heifers (n = 109) under the same nutrition and management conditions underwent AI with the semen samples. All inseminations were done by the same technician and donor bulls were used consecutively throughout the breeding season. Pregnancy diagnosis was done by ultrasound images (Falco 100, 6 MHz, Pie Medical, Crawley, UK) 28 days after insemination. The SISVAR software was used for variance analysis and comparison of means by Tukey test at a nominal level of 5%. The IM (194.13 ± 31.99) obtained from 10 illuminations per sample of each bull and the conception rate (CR) of group I (CR = 0.63 ± 0.49) differed (P < 0.05) compared with group II (IM = 142.03 ± 30.62; CR = 0.43 ± 0.50). Pearson correlation coefficient (P < 0.05) between IM and CR was r = 0.21, showing coherence with IM and CR, despite its low value. These data showed that second-order statistics are correlated to semen fertility and could be used to evaluate ejaculates of the bull. Financial support: FAPEMIG grant EDT 94/07 and CNPq.

Download Full-text

PROTECTIVE EFFECT OF CARNITINE (ST-261, SIGMA-TAU) IN ACUTE MYOCARDIAL INFARCTION IN DOGS

10.1055/s-0038-1643012 ◽

1987 ◽

Author(s):

K Kordenat ◽

J Leasure

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Protective Effect ◽

Myocardial Necrosis ◽

Control Group ◽

Computer Technique ◽

T Wave ◽

Group I ◽

The Mean ◽

Group Ii

Limitation of infarct size (IS), using ST-261, was evaluated in a group (I) of eight dogs, during acute MI. Another group (II) served as the control group. The protocol for both groups was the same except that each dog in the treated group was ST-261 as a single bolus (25 mg/kg, in 20ml normal saline), before inducing an occluding thrombus in the mid-LAD, using a closed-chest model, under x-ray visualization. Percentages of total (gms) myocardium at jeopardy (TMJW) and myocardial necrosis (TMNW), delineated by fluoroscein and TTC dyes, respectively, were calculated and compared to the total ventricular myocardial weight (TVMU), by computer technique for both groups at 3 Hrs post-occlusion of the LAD. Mean serum total CPK (CPK-t) and isozymes (mb-band) were measured before and up to 3 Hrs post-occlusion, as were various hemodynamic and mean precordial (21 lead) ST-segment and T-wave amplitudes. There was 14% less TMJU (p<0.05) and 41% less TMNW (p<0.01) in Group I compared to Group II. The mean % of CPK-mb/CPK-t decreased in I and increased in II over the 3 Hrs of observation. Mean HR decreased (p<0.01) in I compared to II at 3 Hrs postocclusion. The sum of the mean T-wave amplitudes from the precordial electrode sites was less in I at 3 Hrs. It is felt that ST-261 had a protective effect on the myocardium during acute myocardial infarction.

Download Full-text

Protective effect of resveratrol against corticosterone-induced neurotoxicity in PC12 cells

Translational Neuroscience ◽

10.1515/tnsci-2019-0038 ◽

2019 ◽

Vol 10 (1) ◽

pp. 235-240 ◽

Cited By ~ 3

Author(s):

Ye Zhang ◽

Yun He ◽

Ning Deng ◽

Yan Chen ◽

Jiecong Huang ◽

...

Keyword(s):

Protein Expression ◽

Protective Effect ◽

Cell Viability ◽

Pc12 Cells ◽

Caspase 3 ◽

Annexin V ◽

Cell Counting ◽

Depressant Effect ◽

Protective Efficiency ◽

Related Proteins

Abstract Objective Resveratrol(RES) is a natural polyphenol which possesses an anti-depressant effect. However, the mechanisms of its anti-depressant effect remain unclear. The aim of the study is to investigate the potential mechanisms in the neuro-protective efficiency in the corticosterone-induced pheochromacytoma 12 (PC12) cells. Methods PC12 cells were treated with 200 μM of corticosterone in the absence or presence of different concentrations of RES for 24 h. Then, cell viability was measured by Cell Counting Kit-8 assay. Apoptosis of PC12 cells was measured by Annexin V-FITC and Propidium iodide (PI) labelling. The expression of apoptosis-related proteins including Bax, Bcl-2, caspase-3 was determined by western blotting. Results The results showed that treatment with 200 μM of corticosterone induced cytotoxicity in PC12 cells. However, different concentrations of RES (2.5μmol/L, 5μmol/L and 10 μmol/L) significantly increased the cell viability, suppressed the apoptosis of PC12 cells, down-regulated Bax and caspase-3 protein expression, and up-regulated Bcl-2 protein expression, compared to the model group (p<0.05). Conclusion Resveratrol has a protective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to the apoptosis via inhibition of apoptosis-related proteins and displays the antidepressant-like effect.

Download Full-text

Desoxyrhapontigenin attenuates neuronal apoptosis in an isoflurane-induced neuronal injury model by modulating the TLR-4/cyclin B1/Sirt-1 pathway

AMB Express ◽

10.1186/s13568-020-01105-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Feng Liang ◽

Xin Fu ◽

Yunpengfei Li ◽

Fanglei Han

Keyword(s):

Oxidative Stress ◽

Cognitive Function ◽

Protein Expression ◽

Protective Effect ◽

Neuronal Apoptosis ◽

Caspase 3 ◽

Neuronal Injury ◽

Cyclin B1 ◽

The Brain ◽

And Oxidative Stress

Abstract This study investigated the protective effect of desoxyrhapontigenin (DOP) against isoflurane (ISF)-induced neuronal injury in rats. Neuronal injury was induced in pups by exposing them to 0.75% ISF on postnatal day 7 with 30% oxygen for 6 h. The pups were treated with DOP 10 mg/kg, i.p., for 21 days after ISF exposure. The protective effect of DOP was estimated by assessing cognitive function using the neurological score and the Morris water maze. Neuronal apoptosis was assessed in the hippocampus using the TUNEL assay, and protein expression of caspase-3, Bax, and Bcl-2 was measured by Western blotting. The levels of cytokines and oxidative stress parameters were assessed by ELISA. Western blotting and RT-PCR were performed to measure the expression of NF-kB, TLR-4, Sirt-1, and cyclin B1 protein in the brain. The cognitive function and neurological function scores were improved in the DOP group compared with the ISF group. Moreover, DOP treatment reduced the number of TUNEL-positive cells and the expression of caspase-3, Bax, and Bcl-2 protein in the brains of rats with neuronal injury. The levels of mediators of inflammation and oxidative stress were reduced in the brain tissue of the DOP group. Treatment with DOP attenuated the protein expression of TLR-4, NF-kB, cyclin B1, and Sirt-1 in the brain tissue of rats with neuronal injury. In conclusion, DOP ameliorates neuronal apoptosis and improves cognitive function in rats with ISF-induced neuronal injury. Moreover, DOP treatment can prevent neuronal injury by regulating the TLR-4/cyclin B1/Sirt-1 pathway.

Download Full-text

Protective Effect of Two Alkaloids from Hippophae rhamnoides Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts

Molecules ◽

10.3390/molecules26071946 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1946

Author(s):

Wenna Zhou ◽

Jian Ouyang ◽

Na Hu ◽

Gang Li ◽

Honglun Wang

Keyword(s):

Protein Expression ◽

Protective Effect ◽

Caspase 3 ◽

Cardiac Cells ◽

Potential Candidate ◽

H9c2 Cells ◽

Cardiac Muscle Cells ◽

Anti Cancer ◽

H9c2 Cardiomyoblasts ◽

Induced Apoptosis

Background: Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, clinical application with Dox is limited due to its potentially fatal cumulative cardiotoxicity. N-p-coumaroyl-4-aminobutan-1-ol (alk-A), an organic amide alkaloid and hippophamide (alk-B), a rare pyridoindole alkaloid were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of alk-A and alk-B against Dox-induced embryonic rat cardiac cells (H9c2 cells) apoptosis. Methods: H9c2 cells were treated with Dox (2.5 µM) in the presence of alk-A and alk-B (10, 20, and 40 µM) and incubated for 24 h. Results: It was shown that pretreatment of the H9c2 cells with alk-A and alk-B significantly reduced Dox-induced apoptosis. Alk-A and alk-B both inhibited reactive oxygen species (ROS) production and suppressed cleaved-caspase-3 protein expression and the activation of JNK (Jun N-terminal kinases), as well as increasing ATP levels, favoring mitochondrial mitofusin protein expression, and relieving damage to mitochondrial DNA. Conclusions: These results suggest that alk-A and alk-B can inhibit Dox-induced apoptosis in H9C2 cardiac muscle cells via inhibition of cell apoptosis and improvement of mitochondrial function, while alk-B showed more protection. Alk-B could be a potential candidate agent for protecting against cardiotoxicity in Dox-exposed patients.

Download Full-text

The Effects of Pumpkin Seed Oil on Carbon Tetrachloride Induced Chronic Hepatic Damage in Rats and Detection of Hepatic Apoptosis by Caspase Activity

Indian Journal of Animal Research ◽

10.18805/ijar.b-1145 ◽

2020 ◽

Author(s):

Gorkem Ekebas ◽

Ayhan Atasever ◽

Meryem Senturk ◽

Duygu Yaman Gram ◽

Meryem Eren

Keyword(s):

Carbon Tetrachloride ◽

Biochemical Parameters ◽

Caspase 3 ◽

Seed Oil ◽

Corn Oil ◽

Group Vi ◽

Pumpkin Seed ◽

Group I ◽

Pumpkin Seed Oil ◽

Group Ii

The present study determined the possible protective effect of pumpkin seed oil (PSO) on cellular apoptosis detection by immunehistochemical method (with (active) caspase-3, -4, 8 and -9 antibodies) in liver tissue and some biochemical parameters; serum ALT activity, vitamin E, plasma 8-OHdG and liver MDA levels, SDH and GPx activities on chronic liver injury induced by carbon tetrachloride (CCl4) in rats. A total of 80 Wistar rats were divided into eight groups of ten rats each: Group I served as control, receiving vehicle 0.9% NaCl (1.0 mL/kg); Group II was given intraperitoneally CCl4 at a dose of 0.2 mL/kg, 1:1 mixture with corn oil, twice a week for 8 weeks. Groups III, IV and V were daily treated with PSO through gavage for 8 weeks (1, 2 and 3 mL/kg, respectively). Groups VI, VII and VIII were administered with intraperitoneally CCl4 (0.2 mL/kg) twice a week and simultaneously PSO by gavage for 8 weeks (1, 2 and 3 mL/kg, respectively). Groups VII and VIII were showed a partial decrease of steatosis in the hepatocytes while the findings in the Group VI were similar to Group II. Compared to Group II, the severity of caspase-3, -8 and -9 activities were not changed in the Group VI but Group VII and VIII were partially reduced. As a result, although no positive effect of 1 mL/kg PSO on liver damage was observed, it has been concluded that PSO has some ameliorative effects by decreasing the levels of biochemical parameters and histopathology in 2 and 3 mL/kg PSO groups. Dose and duration dependent further investigations need to be performed to understand the dose that produces the best result without any side effect.

Download Full-text

Protective effect of N-acetylcysteine on kidney as a remote organ after skeletal muscle ischemia-reperfusion

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000900004 ◽

2012 ◽

Vol 27 (9) ◽

pp. 611-615 ◽

Cited By ~ 13

Author(s):

Mohammad Ashrafzadeh Takhtfooladi ◽

Amirali Jahanshahi ◽

Gholamreza Jahanshahi ◽

Amir Sotoudeh ◽

Hamed Ashrafzadeh Takhtfooladi ◽

...

Keyword(s):

Skeletal Muscle ◽

Protective Effect ◽

Femoral Artery ◽

Renal Injury ◽

Ischemia Reperfusion ◽

Male Rats ◽

Muscle Ischemia ◽

Group I ◽

Remote Organ ◽

Group Ii

PURPOSE: To investigate whether N-acetylcysteine has a protective effect against renal injury as a remote organ after skeletal muscle ischemia-reperfusion in rats. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I) and group ischemia-reperfusion + N-acetylcysteine (group II). After ketamine and xylazine anesthesia, femoral artery was exposed. All animals were undergone 2h of ischemia by occlusion femoral artery and 24h of reperfusion. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mg/kg-¹, immediately before reperfusion. After 24h of reperfusion, the blood samples were collected and submitted for evaluation of plasmatic urea, creatinine values and then rats were euthanized and left kidney harvested for histopathological analysis under light microscopy. RESULTS: The urea (35±7.84 mg.dL-1), creatinine (1.46±0.47 mg.dL-1) values were significantly lower in group II (P=0.000). Renal histopathologic study in group I showed extensive distal and proximal tubular cells necrosis and sloughing of epithelial cells into the tubular lumen, cast formation in tubule and glomerul, glomerul fibrosis and hemorrhage. Histopathologically, there was a significant difference (p=0.037) between two groups. CONCLUSION: The N-acetylcysteine was able to decrease renal injury induced by skeletal muscle ischemia reperfusion in rats.

Download Full-text

Study of the antineoplastic action of Tabebuia avellanedae in carcinogenesis induced by azoxymethane in mice

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502011000200009 ◽

2011 ◽

Vol 26 (2) ◽

pp. 125-128 ◽

Cited By ~ 7

Author(s):

Roberta Alves Higa ◽

Ricardo Dutra Aydos ◽

Iandara Schettert Silva ◽

Rondon Tosta Ramalho ◽

Albert Schiaveto de Souza

Keyword(s):

Protective Effect ◽

Colon Carcinogenesis ◽

Group Iv ◽

Aberrant Crypt Foci ◽

Antitumor Action ◽

Group V ◽

Group Iii ◽

Antineoplastic Action ◽

Group I ◽

Group Ii

PURPOSE: To study the antitumor action of Tabebuia avellanedae in experimentally induced colon carcinogenesis by azoxymethane in mice. METHODS: Fifty (n=50) mice were divided into five groups: in group I azoxymethane (AOM) was administered, in Group II - β-lapachone, in group III - vehicle (diluent) and in group IV - vehicle + AOM and finally in group V - β-lapachone + AOM. RESULTS: It was observed the presence of aberrant crypt foci in all animals of groups I and IV, 50% in group II and 90% in group V. CONCLUSION: The β-lapachone extracted from the Tabebuia avellanedae showed no protective effect of lesions induced by azoxymethane in colon of mice.

Download Full-text