scholarly journals Allopurinol and Febuxostat Equally Attenuate Methotrexate-Induced Testicular Injury In Rats Via Activation Of EGF/ ERK1/2/HO‐1 Signaling Pathway.

2021 ◽  
Author(s):  
Remon R Rofaeil ◽  
Mohamed A. Ibrahim ◽  
Reham H. Mohyeldin ◽  
Walaa Y. Abdelzaher
Keyword(s):  
Protective Effect ◽  
Histopathological Examination ◽  
Serum Testosterone ◽  
Free Testosterone ◽  
Testicular Tissue ◽  
Testicular Damage ◽  
Purine Analogue ◽  
Tnf Α ◽  
Significant Difference ◽  
Testicular Injury

Abstract Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. In the current study, we evaluated the possible protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Gonadotoxicity was induced by a single dose of MTX (20 mg/kg, i.p.). ALL and FEB were administered orally in the following daily doses (100, 10 mg/kg, respectively) for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and nitric oxide (NO) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NO, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. In conclusion, All and FEB were protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions which might be through activation of the EGF/ERK1/2/HO-1 pathway. At the same time, no significant difference between ALL and FEB was noticed in this protective effect.

Long-Term Protective Effect of N-Acetylcysteine against Amikacin-Induced Ototoxicity in End-Stage Renal Disease: A Randomized Trial

2018 ◽  
Vol 38 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Alperen Vural ◽  
İsmail Koçyiğit ◽  
Furkan Şan ◽  
Eray Eroğlu ◽  
İbrahim Ketenci ◽  
...  
Keyword(s):  
Protective Effect ◽  
Pure Tone Audiometry ◽  
The Other ◽  
Control Group ◽  
Tnf Α ◽  
Significant Difference ◽  
Hearing Test ◽  
Stage Renal Disease ◽  
End Stage

Background The aim of the study is to evaluate the long-term protective effect of N-acetylcysteine (NAC), an antioxidant agent, against aminoglycoside (AG)-induced ototoxicity. Methods A total of 40 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and having their first peritonitis attacks and planned to be treated with AGs were enrolled in the study. They were randomized into 2 groups: 1 group received additional NAC and the other did not. All patients underwent hearing tests with pure tone audiometry (PTA) after the diagnosis, at 1 month and 12 months and at the same time the tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Results Patients taking NAC had better hearing test results in both ears at 1 month except 2,000 Hz for the left ear, which wasn't significantly different between the 2 groups. Although patients taking NAC had generally better PTA results at 12 months, differences between the 2 groups were not statistically significant. Baseline IL-6 level was significantly higher in the NAC group than the control group. Both TNF-α and IL-6 levels at 1 month were significantly lower in the NAC group than in the control group. On the other hand, there was no significant difference between the 2 groups in terms of TNF-α and IL-6 levels at 12 months. Conclusions The results of the current study showed that NAC, a potent anti-inflamatory drug, may be otoprotective, but that the effect is not long-lasting.

scholarly journals The Effect of Infliximab on Intestinal Anastomosis Healing in Rats

2016 ◽  
Vol 117 (2-3) ◽  
pp. 108-116 ◽  
Author(s):  
Oktay Karaköse ◽  
Hüseyin Eken ◽  
Ali Naki Ulusoy ◽  
Hüseyin Koray Topgül ◽  
Mehmet Bilgin ◽  
...  
Keyword(s):  
Single Dose ◽  
Histopathological Examination ◽  
Intestinal Anastomosis ◽  
Bursting Pressure ◽  
Infliximab Treatment ◽  
Hydroxyproline Concentration ◽  
Tnf Α ◽  
Significant Difference ◽  
Negative Effect ◽  
Anastomosis Healing

Intestinal anastomosis healing is a complex physiological process in which many local and systemic factors play a role. One of the significant cytokines in this process is TNF-α. Infliximab is a chimeric monoclonal antibody which binds to TNF-α with high affinity. Although this agent is used in ulcerative colitis and Crohn’s disease, intestinal surgery may be required in these patients. In this study it was aimed to determine whether or not there was any negative effect of preoperative single dose infliximab treatment on intestinal anastomosis healing. Two groups of 10 rats were formed. One of these groups was administered with a single dose of infliximab 8 mg/kg as a 20-minute intravenous infusion from the femoral vein. Four days after the infusion, a full layer incision was made to the colon and anastomosis was applied to all the rats. At 7 days after anastomosis, the subjects were sacrificed. The anastomosis segment was removed and the bursting pressure was measured. Tissue samples were taken from this segment for hydroxyproline concentration and histopathological examination. A blood sample was taken to measure TNF-α values. No statistically significant difference was determined between the groups in terms of bursting pressure, tissue hydroxyproline concentration or histopathological scoring. A single dose of 8 mg/kg infliximab administered 4 days preoperatively was not found to have any negative effect on intestinal anastomosis healing in rats.

scholarly journals Royal Jelly Abrogates Cadmium-Induced Oxidative Challenge in Mouse Testes: Involvement of the Nrf2 Pathway

2018 ◽  
Vol 19 (12) ◽  
pp. 3979 ◽  
Author(s):  
Rafa Almeer ◽  
Doaa Soliman ◽  
Rami Kassab ◽  
Gadah AlBasher ◽  
Saud Alarifi ◽  
...  
Keyword(s):  
Royal Jelly ◽  
Histopathological Examination ◽  
Physiological Saline ◽  
Serum Testosterone ◽  
Testicular Tissue ◽  
Redox Status ◽  
Nuclear Antigen ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Oxidative Challenge

The current study examined the efficacy of royal jelly (RJ) against cadmium chloride (CdCl2)-induced testicular dysfunction. A total of 28 Swiss male mice were allocated into four groups (n = 7), and are listed as follows: (1) the control group, who was intraperitoneally injected with physiological saline (0.9% NaCl) for 7 days; (2) the RJ group, who was orally supplemented with RJ (85 mg/kg daily equivalent to 250 mg crude RJ) for 7 days; (3) the CdCl2 group, who was intraperitoneally injected with 6.5 mg/kg for 7 days; and (4) the fourth group, who was supplemented with RJ 1 h before CdCl2 injection for 7 days. Cd-intoxicated mice exhibited a decrease in serum testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. A disturbance in the redox status in the testicular tissue was recorded, as presented by the increase in lipid peroxidation and nitrate/nitrite levels and glutathione (GSH) depletion. Moreover, the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) and their gene expression were inhibited. In addition, interleukin-1ß (IL-1β) and tumor necrosis factor-α (TNF-α) levels were elevated. Furthermore, Cd triggered an apoptotic cascade via upregulation of caspase-3 and Bax and downregulation of Bcl-2. Histopathological examination showed degenerative changes in spermatogenic cells, detachment of the spermatogenic epithelium from the basement membrane, and vacuolated seminiferous tubules. Decreased cell proliferation was reflected by a decrease in proliferating cell nuclear antigen (PCNA) expression. Interestingly, RJ supplementation markedly minimized the biochemical and molecular histopathological changes in testes tissue in response to Cd exposure. The beneficial effects of RJ could be attributed to its antioxidative properties.

scholarly journals Protective effect of hydroalcoholic extract of Teucrium polium on diabetes-induced testicular damage and serum testosterone concentration

2017 ◽  
Vol 15 (4) ◽  
pp. 195-202 ◽  
Author(s):  
Ramin Salimnejad ◽  
Ghasem Sazegar ◽  
Mohammad Javad Saeedi Borujeni ◽  
Seyed Mojtaba Mousavi ◽  
Fatemeh Salehi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Serum Testosterone ◽  
Testicular Damage ◽  
Hydroalcoholic Extract ◽  
Testosterone Concentration ◽  
Teucrium Polium

scholarly journals Effects of Withania coagulans extract and morphine on spermatogenesis in rats

2021 ◽  
Vol 18 (4) ◽  
pp. 817-822
Author(s):  
Ali Noori ◽  
Leila Amjad ◽  
Fereshteh Yazdani
Keyword(s):  
Body Weight ◽  
Luteinizing Hormone ◽  
Methanol Extract ◽  
Histopathological Examination ◽  
Follicle Stimulating Hormone ◽  
Testicular Tissue ◽  
Reproductive Parameters ◽  
Blood Samples ◽  
Significant Difference ◽  
Sistan And Baluchestan

Purpose: To investigate the comparative effects of Withania coagolans extract and morphine on spermatogenesis in rats Methods: W. coagolans was collected from Sistan and Baluchestan, Iran and 50 and 100 mg/kg body weight doses of methanol extract and 5, 10 and 15 mg/kg body weight doses of morphine were administered parenterally to the rats which were divided into groups. Blood samples were collected and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were assayed. The testicular tissue was isolated for histopathological examination. Results: No significant changes were observed in levels of LH, FSH and testosterone in treated groups (p < 0.05). However, there was significant difference between the treated groups for extract plus morphine groups, in terms of the number of spermatogonium, spermatocytes and spermatide variation. Moreover, the results indicate tissue disorders in all groups relative to control. The extract caused more disturbances in spermatogenesis compared to morphine, and appears to improve parameters related to spermatogenesis. Conclusion: The results show that the higher dose of Withania coagolans extract (100 mg/kg) exerts varying effects on reproductive parameters. Moreover, the lower dose of Withania coagolans extract (50 mg/kg) enhanced spermatogenesis while also protecting against the damaging effects of morphine.

scholarly journals The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 223 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Asmaa M. Abdel-Aziz ◽  
Sara M. N. Abdel-Hafez ◽  
Katharigatta N. Venugopala ◽  
Anroop B. Nair ◽  
...  
Keyword(s):  
Protective Effect ◽  
Testosterone Level ◽  
Caspase 3 ◽  
Cell Damage ◽  
Necrosis Factor Alpha ◽  
P Glycoprotein ◽  
Testicular Weight ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Testicular Injury

Paeonol, a phenolic ingredient in the genus Paeonia, possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood–testis barrier. The present study evaluated the protective effect of paeonol on MTX-induced testicular injury in rats with the exploration of its mechanism and the possible contribution of P-gp in such protection. Testicular weight, serum testosterone, and testicular P-gp levels were measured. Testicular oxidant/antioxidant status was evaluated via determining the levels of malondialdehyde, total nitrite, reduced glutathione, and superoxide dismutase activity. The inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the apoptotic marker caspase 3 were estimated immunohistochemically. Testicular histopathology and spermatogenesis scores were also examined. MTX caused histopathologically evident testicular damage with decreased testicular weight, testosterone level, and spermatogenesis score, as well as significant increases in oxidative, inflammatory, and apoptotic responses. Paeonol significantly restored testicular weight, testosterone level, spermatogenesis score, and oxidant/antioxidant balance. Moreover, paeonol increased the testicular P-gp level and significantly decreased TNF-α and caspase 3 immunostaining. In conclusion, paeonol offered a protective effect against MTX-induced testicular injury through its antioxidant, anti-inflammatory, and antiapoptotic effects, as well as by increasing testicular P-gp level.

Protective effect of telmisartan treatment against arsenic-induced testicular toxicity in rats

2015 ◽  
Vol 70 (7-8) ◽  
pp. 175-181 ◽  
Author(s):  
Amr A. Fouad ◽  
Waleed H. Albuali ◽  
Abdulruhman S. Al-Mulhim ◽  
Iyad Jresat
Keyword(s):  
Nitric Oxide ◽  
Protective Effect ◽  
Sodium Arsenite ◽  
Nitrosative Stress ◽  
Testicular Tissue ◽  
Myeloperoxidase Activity ◽  
Potential Candidate ◽  
Testicular Damage ◽  
Angiotensin Ii Receptor ◽  
Anti Inflammatory

Abstract Oxidative/nitrosative stress, inflammation, and apoptosis play a crucial role in the pathogenesis of arsenic-induced testicular injury. Telmisartan, the angiotensin II-receptor antagonist, possesses antioxidant and anti-inflammatory activities. The protective effect of telmisartan against arsenic-induced testicular damage was investigated in rats. Testicular damage was induced by sodium arsenite (10 mg kg–1/day, p.o., for 2 consecutive days). Telmisartan (10 mg kg–1/day, i.p.) was given for 3 consecutive days, starting 1 day before sodium arsenite administration. Telmisartan significantly attenuated the arsenic-induced decrease in the levels of serum testosterone and testicular reduced glutathione, and significantly decreased the elevation of the levels of testicular malondialdehyde, nitric oxide, and arsenic levels, as well as myeloperoxidase activity resulting from sodium arsenite administration. Histopathological and immunohistochemical examination revealed that telmisartan markedly attenuated testicular tissue changes, and decreased the arsenic-induced expression of vascular endothelial growth factor, inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, and caspase-3. Telmisartan, via its antioxidant and/or anti-inflammatory effects, may represent a potential candidate to protect against the deleterious effects of arsenic on testicular tissue.

scholarly journals Safety and toxicity of human limbus-derived stromal/mesenchymal stem cells with and without alginate encapsulation for clinical application

2021 ◽  
Author(s):  
Mukesh Damala ◽  
Naveen Pakalapati ◽  
Vivek Singh ◽  
Sayan Basu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Histopathological Examination ◽  
Systemic Toxicity ◽  
Mycoplasma Species ◽  
Corneal Tissue ◽  
Alginate Encapsulation ◽  
Tnf Α ◽  
Significant Difference

Abstract Background The purpose of this study was to assess the ocular and systemic toxicity of topically applied human limbus-derived stromal/mesenchymal stem cells (hLMSCs) with and without alginate encapsulation as per Indian regulatory guidelines for stem cell therapy. Methods The hLMSCs were obtained from cadaveric corneoscleral rims and expanded in a current good manufacturing practice compliant laboratory. The hLMSCs were checked for viability, chromosomal stability, growth kinetics, contamination, and endotoxin levels. Cells with (En+ hLMSCs) or without (En− hLMSCs) alginate encapsulation were used for the animal experiments. The study involved 3 groups of 6 New Zealand white rabbits each, which underwent corneal wounding followed by treatment with sham (G1), En− hLMSCs (G2), and En+ hLMSCs cells (G3). Ophthalmic assessment including intraocular pressure (IOP), blood investigations and inflammatory marker (IL-6, TNF-α, IgE) expression in serum and tears were assessed on days 1, 7, 14, 21, and day 28. At the end of 28 days, the animals were sacrificed, and the organs were subjected to histopathological examination. Results The hLMSCs had 88.33 ± 2.37% viability at the end of 6 hours and 78.21 ± 1.47% at the end of 24 hours. The cells showed positive expression for the stem-cell biomarkers (p63α, Pax6, and ABCG2), extracellular matrix marker (Col-III) and mesenchymal biomarkers (VIM, CD73, CD90 and CD105). No contamination by the Mycoplasma species was found in either of the En-/En + hLMSCs and the levels of bacterial endotoxins in the En- hLMSCs and En + hLMSCs cell suspension was found be within the permissible levels (≤ 0.12 EU/mL). Ophthalmic examination showed no significant difference in IOP, corneal clarity and conjunctival congestion between the three groups at every time point. Haematological parameters were comparable between the three groups. The inflammatory markers in tear and serum (TNF-α and IL-6) were not significantly elevated in the groups receiving En+/En− hLMSCs. Histological examination did not show any abnormality in the ocular or corneal tissue, and the viscera. Conclusions The results of the study show that hLMSCs do not cause any local or systemic toxicity in recipients, implying that these cells are safe for clinical use and their efficacy can be assessed in human clinical trials.

scholarly journals Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 632 ◽  
Author(s):  
Maria Adriana Neag ◽  
Adrian Catinean ◽  
Dana Maria Muntean ◽  
Maria Raluca Pop ◽  
Corina Ioana Bocsan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Hepatic Injury ◽  
Liver Toxicity ◽  
Histopathological Examination ◽  
Plasma Concentrations ◽  
Control Group ◽  
Apap Overdose ◽  
Group I ◽  
Tnf Α ◽  
Bacillus Spores

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1β). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1β, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent—silymarin.

The effect of bee pollen on reproductive and biochemical parameters in methotrexate-induced testicular damage in adult rats

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ozlem Saral ◽  
Eda Dokumacioglu ◽  
Sinan Saral ◽  
Aysegul Sumer ◽  
Ozgur Bulmus ◽  
...  
Keyword(s):  
Testosterone Level ◽  
Serum Testosterone ◽  
Male Rats ◽  
Control Group ◽  
Testicular Damage ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Adult Rats ◽  
Bee Pollen ◽  
Testicular Injury

AbstractObjectivesMethotrexate (MTX) is an anticancer drug used in chemotherapy. MTX was known for its toxic effects involving most of the organs including testis. Bee pollen is healthy food for human and has antioxidant effect. We intended to determine protective effect of bee pollen against testicular injury caused by MTX in rats.MethodsThirty-two adult Sprague Dawley male rats were used, and 4 groups were formed: control, MTX, pollen, and MTX + pollen. Rats were given pollen at a dose of 400 mg/kg with intragastric gavage for 10 days. On day 7, MTX was administered a single dose of 30 mg/kg ip. Serum testosterone and LH, tissue MDA level, and SOD and CAT enzyme activities were examined. In addition, spermatological parameters were evaluated.ResultsMDA level and SOD activity increased while testosterone level decreased significantly in the MTX group compared to the control group. In the MTX + pollen group, MDA level and SOD activity decreased while testosterone level increased. There was no significant change in CAT activity and LH values. Abnormal sperm ratio decreased in the MTX + pollen group compared to the MTX group.ConclusionsOur results suggest that bee pollen has a healing effect on reproductive parameters in testicular damage caused by MTX.

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