scholarly journals Protective effects of curcumin against methotrexate-induced testicular damage in rats by suppression of the p38-MAPK and nuclear factor-kappa B pathways

Author(s):  
Leyla Kilinc ◽  
Yesim Hulya Uz

Objective: Methotrexate (MTX), is a commonly used chemotherapeutic agent. This study aimed to investigate the possibility that curcumin (CMN) protects against MTX-induced testicular damage by affecting the phospho (p)-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways. Methods: Male Wistar albino rats were subdivided into three groups. The control group was given an intragastric (ig) administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal (ip) dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given ig CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single ip dose of MTX (20 mg/kg) on the 11th day. Results: The animal weights, the seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. The testes weight and the ratio of the testes to body weight did not change, whereas the number of seminiferous tubules and the interstitial space width increased significantly in the MTX group. The number of phospho-p38 (p-p38) MAPK immunopositive cells and the immunoreactivity of NF-kB also increased in the MTX group compared to the control group. Conclusion: CMN prevented the MTX-induced decreases in the body weight, seminiferous tubule diameter, and the germinal epithelium height, while significantly reducing the number of histologically damaged seminiferous tubules and the interstitial space width changes due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-kB immunoreactivity.

2021 ◽  
pp. 096032712110356
Author(s):  
Ozlem Delen ◽  
Yesim H Uz

The aim of the study was to investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) against methotrexate (MTX)-induced testicular damage in rats. Forty Wistar albino male rats were divided into equally four groups: Control group (saline solution, IP), PDTC group (100 mg/kg PDTC,IP, 10 days), MTX group (20 mg/kg MTX, IP, single dose, on the 6th day) and MTX + PDTC group (100 mg/kg PDTC, IP, 10 days and 20 mg/kg MTX, IP, single dose, on the 6th day). After 10 days, testicular tissues were excised for morphometric, histological and immunohistochemical evaluations. Serum testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and prokineticin 2 (PK2) levels were determined. Body and testicular weights were measured. Testicular damage was assessed by histological evaluation. Nuclear factor kappa B (NFkB), nuclear factor erythroid 2 related factor 2 (Nrf2) and PK2 immunoreactivities were evaluated by HSCORE. Body and testicular weights, serum FSH, LH, testosterone levels, seminiferous tubule diameter and germinal epithelial thickness were significantly decreased in the MTX group. However, serum PK2 level, histologically damaged seminiferous tubules and interstitial field width were significantly increased. Additionally, there was an increase in NFkB and PK2 immunoreactivity, whereas there was a significant decrease in Nrf2 immunoreactivity. PDTC significantly improved hormonal, morphometric, histological and immunohistochemical findings. Taken together, we conclude that PDTC may reduce MTX-induced testicular damage via NFkB, Nrf2 and PK2 signaling pathways.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Mohamed Kh. ElMahdy ◽  
Samar A. Antar ◽  
Ehab Kotb Elmahallawy ◽  
Walied Abdo ◽  
Hayfa Hussin Ali Hijazy ◽  
...  

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.


Author(s):  
R Islam ◽  
N Sultana ◽  
U Ayman ◽  
A Akter ◽  
M Afrose ◽  
...  

Glucocorticoids (GCs) cause excess fat accumulation, which leads to fertility dysfunction in broilers. The study investigated alterations in the morphology and morphometry of the testes of broilers in response to GC and dexamethasone (DEX). Male day-old chicks were randomly divided into a control group and three experimental groups (E1, E2, and E3). The control group was fed a commercial broiler ration. The experimental groups were fed a commercial broiler ration containing GC (i.e. DEX 3, 5, and 7 mg/kg, respectively). The testes were collected and stained with haematoxylin and eosin to count the number of testicular seminiferous tubules. An increase in the seminiferous tubule count was initially seen, which declined as both the age of the broilers and the dose of DEX increased. Morphometric measurements, i.e., the testicular capsule thickness, seminiferous tubule diameter, and seminiferous epithelium height, were performed. The initial thickening of the testicular capsule was evident. There was a depletion of the interstitial (Leydig) cell population in the experimental groups with the age and increased with the dose advancement. The diameter of the seminiferous tubules and testicular capsule thickness remained upregulated in the treatment groups with the increased dose of DEX. The initial height of the seminiferous epithelium increased in the experimental groups of broilers. The study suggests that DEX greatly alters the morphological architecture of broiler testes; as a result, it could be said that DEX has the effect on the infertility of the broiler by affecting the morphology as well as the functionality of the testes.


2018 ◽  
Vol 30 (2) ◽  
pp. 17-22
Author(s):  
Aseel J. Ibraheem ◽  
Aysar N. Mohammed

Background: All diseases concerning bone destruction such as osteoporosis and periodontal diseases share common pattern in which the osteoclast cells are absolutely responsible for bone resorption that occurred when osteoclast activity exceeds osteoblast activity. Osteoprotegrin (OPG) considered as novel soluble decoy receptor known as “bone protector” since it prevents extreme bone resorption through inhibition of differentiation and activity of osteoclast by competing for binding site. It binds to receptor activator of nuclear factor kappa-B ligand (RANKL) and prevent its interaction with receptor activator of nuclear factor kappa-B (RANK), thus inhibits osteoclast formation. TNF-α is a pro-inflammatory cytokines having a broad range of important roles in regulation of immune system and bone resorption through the stimulation of osteoclastogenesis. Alendronate (ALN) diminishes the expression of osteoclast activating factors and cytokines such as RANKL and enhances the production of decoy receptor osteoprotegerin in osteoblast cells. Moreover, it decreases the production of proinflammatory cytokines such as TNF-α by macrophage, stimulates apoptosis of monocyte-macrophage cell lines derivative and reduces inflammatory response. Aims of the Study: 1. To assess the effect of alendronate treatment on salivary levels of osteoprotegrin and TNF-α in postmenopausal women with osteoporosis and periodontal disease 2. To find any possible correlation between salivary levels of osteoprotegrin and TNF-α in control and study groups. Materials and Methods: Total sample of 90 female subjects (55-65 years) were divided into 3 groups, (30 subjects in each group): first control group involved systemically healthy subjects with healthy periodontium, second group involved postmenopausal women with osteoporosis under alendronate treatment for(3-6)months (alendronate group), third group involved postmenopausal women with osteoporosis without alendronate treatment(osteoporosis group). The last two groups were sub- divided in- to two sub –groups (15 subjects in each sub-group) of gingivitis and periodontitis subjects respectively. Salivary samples were collected from all subjects and salivary levels of osteoprotegrin and TNF- α were determined by enzyme –linked immune sorbent assay (ELISA). Results: Highest median value of salivary (OPG) was found in alendronate group followed by control group while the lowest value was found in osteoporosis group. Highest median value of TNF- α was found in osteoporosis group followed by control group and alendronate group respectively with highly significant differences between them. Spearman correlation between salivary levels of TNF-α and OPG showed non- significant correlation at all subgroups. Conclusion: Subjects with osteoporosis in this study had greater levels of TNF-α and decrease in the level of OPG comparing with patients under alendronate treatment. Alendronate treatment for women with osteoporosis and periodontal disease may have beneficial outcome.


2004 ◽  
Vol 10 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Alifah Hayati ◽  
Binti Yunaida ◽  
I.B. Rai Pidada ◽  
Win Darmanto ◽  
Dwi Winarni

This research has done to investigate the effect of 2-Methoxyethanol on the testicular histology of the male mice and also the influence the length of time after administration 2-ME stopped in the recovery of the spermatogenic cells and the diameter also the thicknes of seminiferous tubule. Thirty BALB/C male mice 8–9 week old, weighed 28–30 grams body weight. Those mice separated to 6 groups with 5 male mice each group. Those mice were treated with 2-ME 200 mg/kg body weight daily by intra peritoneal injection, within 3 weeks (K1). To investigate the influence the length of time after administration 2-ME stopped, the male mice after treated by 2-ME in 3 weeks also given by the length of time after 2-ME administration stopped 1, 2, 3 and 4 weeks (P1, P2, P3 and P4). The control animal given by intraperitoneal administration of saline. Histological observation was performed on the number of spermatogonium, primary spermatocyte, oval spermatid and the diameter also epithelial thickness of seminiferous tubules. The data were analyzed by One-Sample T-test to investigate the differences between K0 and K1. One Way ANOVA to investigate the influence the length of time after 2-ME administration stopped in the P1, P2, P3 and P4 and then continuing by LSD (Least Significant Difference) to show the differences groups of treatment. The result showed that administration 2-ME could destroy the seminiferous tubules in the testes. Its presented by the decreasing of the number spermatogonium, primary spermatocyte, oval spermatid and diameter also epithelial thickness of seminiferous tubule. The length of time after administration 2-ME stopped could recover seminiferous tubules condition. Its presented by the increasing of the number spermatogonium, primary spermatocyte, oval spermatid, and diameter also epithelial tickness of seminiferous tubules. The conclution of this research were, 2-ME could destroy the testicular histology of the male mice and the length of time after administration 2-ME stopped have linear correlation with seminiferous tubules recovery.


2019 ◽  
Vol 12 (8) ◽  
pp. 1261-1265
Author(s):  
Budi Utomo ◽  
Nurfitri Rahmah Daningtia ◽  
Gandul Atik Yuliani ◽  
Wiwik Misaco Yuniarti

Background and Aim: It has long been known that the spermatogenic tissue is very sensitive to temperatures higher than its physiologic temperature and causing cessation of activity and resulting in sterility. This study investigated the effect of a standardized 40% ellagic acid extract of pomegranate on the histopathology, diameter, and epithelial thickness of seminiferous tubules in albino rats exposed to heat. Materials and Methods: Twenty-five male albino Wistar rats were randomized at 7-8 months of age to five treatment groups. Group C was not treated; Group T0 was treated with 0.5% of Na carboxymethyl cellulose (CMC) 2 ml/day and exposed to heat. T1, T2, and T3 were treated with 75, 150, and 300 mg/kg/day of a standardized 40% ellagic acid extract of pomegranate (Punica granatum L.), respectively. The animals were orally administered Na CMC or pomegranate extract and were exposed to sunlight for 15 min at 40°C-42°C for 14 days. The animals were sacrificed on day 15 and the testes were removed for histological evaluation and measurement of seminiferous tubule diameter and epithelium thickness. Results: The diameter of seminiferous tubules from rats exposed to heat and treated with 300 mg/kg/day pomegranate extract was larger and the epithelia thicker than those in the other groups (p= <0.05). The protective effects of the standardized 40% ellagic acid extract may have been mediated by its antioxidant activity. Conclusion: Compared with controls, administration of 300 mg/kg/day of a standardized 40% ellagic acid extract of P. granatum L. for 14 days increased seminiferous tubule diameter and epithelium thickness in albino Wistar rats exposed to heat. Keywords: diameter, epithelium thickness, heat, pomegranate extract, seminiferous tubule.


2017 ◽  
Vol 3 (6) ◽  
pp. 718
Author(s):  
Melyandari Ayu Qomar ◽  
Rimayanti Rimayanti ◽  
Tri Nurhajati

The Objective of this research was to know the effect of laserpuncture on reproduction point of male Mojosari duck on the number of spermatogonium cells and seminiferous tubule diameter of the testes. This research using completely randomized design with eighteen male Mojosari ducks which divided into three group randomly. Group I (P0) without any treatment of laserpuncture, Group II (P1) with 0.2 J dose of laserpuncture, and Group III (P2) with 0.4 J dose of laserpuncture. Laserpuncture shooting was done on reproduction point with three days interval in one month. On the thirty-first day, the duck was dissected so that the testes can be taken then made by the histological slide of testes. The obtained data processed by Analysis of Variant (ANOVA) followed with Duncan. Research result showed that laserpuncture shoot on the reproduction point of five-month-old male Mojosari duck decreases the number of spermatogonium cells and seminiferous tubule diameter of the testes. Keyword: laserpuncture, Mojosari duck, spermatogonium, seminiferous tubule


2007 ◽  
Vol 76 (2) ◽  
pp. 223-229 ◽  
Author(s):  
P. Massányi ◽  
N. Lukáč ◽  
J. Zemanová ◽  
A. V. Makarevich ◽  
P. Chrenek ◽  
...  

The aim of this study was to describe the effects of nickel (NiCl2) on murine testicular structure. Experimental animals were injected intraperitoneally with a single dose of 20 mg NiCl2 per kg of body mass (group A, n = 5) and 40 mg NiCl2 per kg b. m. (group B, n = 5). The group without injection (n = 5) was the control (C). Animals were killed 48 hours after administration of nickel. The body mass of animals, the mass of testes and the testes : body mass ratio were not significantly affected. In both experimental groups a significant (p < 0.001) decrease of germinal epithelium in comparison with control group was observed. The relative volume of the interstitium was increased but not significantly in both experimental groups. An increase in the relative volume of the lumen was registered in both experimental groups in comparison with the control group. The qualitative analysis detected a dilatation of blood vessels in the interstitium, undulation of the basal membrane and several empty spaces in the germinal epithelium. The diameter (n = 150) of the seminiferous tubule was markedly (p < 0.05) decreased in both experimental groups (A, B) compared to control group. The height of the germinal epithelium showed a significant decrease (p < 0.05 - 0.001) after nickel administration. Evaluation of the lumen diameter in the seminiferous tubule showed a significant increase in both experimental groups. The data of the perimeter of seminiferous tubules corresponded with those of the seminiferous tubule diameter. TUNEL assay detected a higher frequency of localized apoptosis in the interstitium of nickel-administered animals compared to control group. Our findings clearly suggest a negative effect of nickel on the structure as well as on the function of the seminferous epithelium at the site of spermatozoa production.


2013 ◽  
Vol 19 (S4) ◽  
pp. 47-48
Author(s):  
M. Ferreira ◽  
T.M. Santos ◽  
M.L. Pereira

Cr(III)-tris(picolinate), [Cr(pic)3], is a very common dietary supplement, recommended for humans, cattle and swine. Chromium is considered an essential trace element, when in oxidation state +3, with some of its compounds seeming to have a beneficial effect on blood sugar regulation mechanisms. However, the safety of the use of a particularly popular Cr(III) compound, ie [Cr(pic)3], remains debatable. Clastogenic, and mutagenic features have been reported by Stearns and co-workers, although surrounded by a controversial and contradictory multitude of publications on this subject. The present work aims to study the effects of [Cr(pic)3] on mice spermatogenesis.Cr(III)-tris(picolinate) was synthesized and characterized according to the literature. Its composition as a mononuclear complex was tested by ESI-MS and by X-ray powder diffraction followed by single-crystal simulation calculations.Male adult CDI mice from Harlan (Spain) were divided in groups and orally given 25 mg/kg and 50 mg/kg/body weigh/daily of [Cr(pic)3] for two weeks. Controls were also done. Behaviour and body weight were monitored throughout the experiments. After sacrifice, testis were collected, weighed, and fixed in Bouin´s solution. Organs were then prepared for histology using routine techniques. Animal experiments were conducted according to ethics procedures. Histological sections of control group evidenced normal regular features (Fig. 1a). However considerable damage was observed in both experimental groups in a dose dependent manner. In fact, seminiferous tubules showed degenerative changes within epithelium, namely vacuolation and sloughing of immature germ cells into the lumen in the group given the lowest dose (Fig.1 b,c). The high dosed group displayed more conspicuous injury within testis, namely strongly atrophic seminiferous tubules devoid of germs cells and strong vacuolation (Figs.1d-f).The results of this study have shown an increased risk of adverse events in mice receiving 50 mg/kg/body weight of [Cr(pic)3]. However, little potential for adverse reproductive and developmental effects namely on progeny was recently described for male mice fed a diet containing 200 mg/kg/day [Cr(pic)3]. In conclusion, concerns about using dietary supplements based on [Cr(pic)3] remain to be elucidated in future work.This work was financed by CICECO, Aveiro University, Portugal.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ng Cho Ping ◽  
Noor Hashida Hashim ◽  
Durriyyah Sharifah Hasan Adli

Twenty-fourSprague-Dawleymale rats (7–9 weeks old, 200–250 g) were divided into Nicotine (N) (0.5 mg/100 g body weight (BW), Nicotine Control (NC) (saline, 0.1 mL/100 g BW),Habbatus saudaoil (HS) (6.0 μL/100 g BW), andHabbatus saudaControl (HSC) (corn oil, 0.1 mL/100 g BW) groups and treated for 100 days. Sperm parameters and seminiferous tubules measurements were evaluated. The N showed a significantly lower sperm motility (1.03±0.05×106 sperm/mL) and percentage of normal (82.61±0.03%) and live (93.88±0.01%) sperm, higher value for the seminiferous tubule (253.36±1.83 μm) and lumen (100.15±2.38 μm) diameters and spermatogonia (19.85±0.39 μm) and spermatocytes (33.37±0.59 μm) layers, and thinner spermatid-sperm layer (22.14±0.71 μm) than the NC (P<0.05). The HS had significantly higher sperm motility (1.49±0.04×106 sperm/mL) and percentage of normal (90.61±0.01%) and live (96.98±0.01%) sperm, smaller lumen diameter (67.53±2.34 μm) and thinner spermatogonia (17.67±0.32 μm) and wider spermatid-sperm (36.95±0.79 μm) layers than the HSC (P<0.05). This research confirmed that nicotine reduced sperm motility and morphology of normal and live sperms and also affected the testis histology, whileHabbatus saudaoil increased sperm quality and gave better testis histological features.


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