Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

Atta, Mustafa S.; Almadaly, Essam A.; El‐Far, Ali H.; Saleh, Rasha M.; Assar, Doaa H.; Jaouni, Soad K. Al; Mousa, Shaker A.

doi:10.3390/ijms18050919

Cited by 100 publications

(89 citation statements)

References 56 publications

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“…This study examines the pathogenic mechanism of ROS/JAK2/NFκB under the condition of hyperglycemia. [34][35][36] Similar to these conclusions, in our study, we also found that the testis weight and sperm motility of DM rats were significantly lower than that of normal rats, and the seminiferous tubules of DM rats were found to be damaged through Wright-Giemsa staining. The above experimental data indicate that DM is indeed prone to impaired reproductive function and spermatogenesis, which is consistent with reports by Maresch CC…”

Section: Discussionsupporting

confidence: 89%

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

et al. 2020

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Background: Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems. Objectives: To delineate the role of ROS/JAK2/NFκB pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NFκB pathway, in the pathogenesis of DM-induced infertility.Methods: 12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4 weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression. Results:Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NFκB pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NFκB pathway, thus inhibiting the apoptosis in the testicular cells of DM rats.Conclusion: ROS/JAK2/NFκB pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in

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Section: Discussionsupporting

confidence: 89%

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

et al. 2020

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“…The percentage of motile sperms was assessed under 400X magnification in at least 10 microscopic fields and being 200 sperms per rat were evaluated. 21 Sperm viability evaluated using eosin-nigrosin staining method. Briefly, 10µL of sperm suspension gently mixed with 10µL eosin-nigrosin solution (containing an equal volume of 1.67% eosin Y and 10% nigrosin) and a smear of the suspension was performed and dried at room temperature.…”

Section: Sperm Evaluationmentioning

confidence: 99%

The Oleo-Gum-Resin of Commiphora myrrha Ameliorates Male Reproductive Dysfunctions in Streptozotocin-Induced Hyperglycemic Rats

et al. 2019

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Background: The oleo-gum-resin of Commiphora myrrha (myrrh) has a long history of therapeutic use in traditional medicine. The aim of this study was to seek for the scientific evidence to determine whether the ethanolic extract of myrrh (EEM) has any beneficial effects on Streptozotocin (STZ) induced testicular impairments, and explore the possible mechanisms underlying such actions. Methods: Forty-eight severe and complicated diabetic rats (fasting blood glucose above 350 mg/dL), randomly were divided into six equal groups (n=8). Besides, eight healthy rats allocated as a normal control group and only treated with vehicle solution. The diabetic animals orally received the extract (100, 200, 300, and 500 mg/kg), metformin (500 mg/kg) or vehicle solution for 28 days. As a final point, plasma glucose and insulin, circulatory sex hormones, sperm parameters including sperm concentration, motility and viability and also testicular malondialdehyde (MDA) levels were assessed. Furthermore, quantitative histological evaluation of seminiferous tubules area and determination of germinal cells apoptosis were performed. Results: None of the studied doses of EEM showed anti-diabetic effects. However, the extract mainly at the maximum dose (500 mg/kg) exhibited beneficial effects on reproductive impairments. The EEM treated rats mainly at 500 mg/kg had significantly higher sperm concentration, sperm motility, sperm viability, sex hormones and lower testicular MDA and germ cell apoptosis index than untreated diabetic rats. Conclusion: These results indicated that EEM may have beneficial effects against reproductive dysfunction induced by diabetes. The mechanisms behind the effects might be associated with the EEM sex hormone booster potential, antioxidant and anti-apoptotic properties.

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“…Several preclinical studies and some clinical reports have demonstrated the favorable euglycemic control, antioxidant, anti-inflammatory, immunomodulatory, anti-dyslipidemic, anti-atherogenic, and broad tissue protective effects of TQ, which collectively appear to be of value in improving DM therapy and alleviating its serious multi-organ complications [15,16,17,18,19,20,21]. In addition, a large body of reports has evidenced that TQ is a highly safe natural agent with no serious toxicity [13,14].…”

Section: Introductionmentioning

confidence: 99%

Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats

El-Shemi¹,

Kensara

Alsaegh³

et al. 2017

Pharmacology

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Aims: This study is aimed at evaluating the antidiabetic effects of thymoquinone (TQ) on streptozotocin (STZ)-induced diabetes in rats, and exploring the possible underlying mechanisms. Methods: Diabetes was induced in adult male Wistar rats by intraperitoneal injection of freshly prepared STZ (65 mg/kg). After disease induction, 42 rats were equally assigned to: controls, STZ-diabetic group, and STZ-diabetic group treated with oral TQ (35 mg/kg/day) for 5 weeks. Fasting blood glucose levels were determined weekly, and the animals were euthanized at day 38 post-STZ injection. Blood samples were assessed for glucose-insulin homeostasis parameters (plasma glucose, glycated hemoglobin, serum insulin, homeostatic model assessment of insulin resistance, and insulin sensitivity index) and lipid profile. Resected pancreases were subjected to histological examination and immunohistochemical or enzyme-linked immunosorbent assay assessment to determine the pancreatic expression of insulin sensitizing β-cells, anti-apoptotic protein “survivin,” apoptosis-inducer “caspase-3,” prototypic angiogenic factors (vascular endothelial growth factor [VEGF] and endothelial cluster of differentiation 31 [CD31]), pro- and anti-inflammatory cytokines (interleukin-1beta [IL-1β] and interleukin-10 [IL-10], respectively), thiobarbituric acid reactive substances (TBARS), total glutathione (GSH), and superoxide dismutase (SOD). The hepato-renal statuses were assessed biochemically and histologically. Results: Therapy with TQ markedly improved the integrity of pancreatic islets, glucose-insulin homeostasis-related parameters, lipid profile parameters, and hepato-renal functional and histomorphological statuses that collectively were severely deteriorated in untreated diabetic group. Mechanistically, TQ therapy efficiently increased insulin producing β-cells, upregulated survivin, VEGF, CD31, IL-10, GSH and SOD, and downregulated caspase-3, IL-1β, and TBARSs in the pancreatic tissues of STZ-diabetic rats. Conclusions: These findings prove the anti-diabetic potential of TQ and its efficacy in regenerating pancreatic β-cells and ameliorating pancreatic inflammation and oxidative stress, and highlight its novelty in repressing apoptosis of β-cells and enhancing islet revascularization in STZ-diabetic rats. Further studies are required to support these findings and realize their possible clinical significance.

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Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

Cited by 100 publications

References 56 publications

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

The Oleo-Gum-Resin of Commiphora myrrha Ameliorates Male Reproductive Dysfunctions in Streptozotocin-Induced Hyperglycemic Rats

Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats

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