scholarly journals Nobiletin Protects Against Diabetes-induced Testicular Injury via Hypophysis-gonadal Axis Up-regulation and Amelioration of Oxidative Stress

2021 ◽  
Author(s):  
Marwa Salah ◽  
Khadiga Ahmed Ismail ◽  
sally mostafa khadrawy
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Androgen Receptors ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
High Dose ◽  
Testicular Injury ◽  
Pro Inflammatory Cytokines

Abstract Background: Testicular injury is one of the most serious problems of Diabetes mellitus. The present study aims to compare the effect of two different doses of nobiletin and the probable mechanisms against diabetes-induced testicular impairment in rats. Methods and Results: Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin (10 mg/kg) or (25 mg/kg) daily and orally for 30 days. Diabetic rats displayed a significant elevation in glucose, glycosylated hemoglobin (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. Levels of serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes with positive caspase-3 and decreased Androgen receptors (AR) immunoexpressions were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. Gene and protein manifestation of LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) was markedly down-regulated in testicular tissues of diabetic group, an effect which was markedly increased with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation, and caspase-3 immuno-expression and improved the activity of the antioxidant enzymes and AR in testicular tissues of diabetic group. Conclusion: Both doses showed protective effects against diabetes-induced testicular injury by diminution of oxidative stress, hyperglycemia, inflammation, caspase-3 and up-regulation of the hypophysis-gonadal axis and androgen receptors. The high dose of nobiletin was more effective than the lower dose.

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary–gonadal axis

2016 ◽  
Vol 94 (6) ◽  
pp. 651-661 ◽  
Author(s):  
Sanaa M. Abd El-Twab ◽  
Hanaa M. Mohamed ◽  
Ayman M. Mahmoud
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Inflammatory Cytokines ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Testicular Damage ◽  
Chronic Hyperglycemia ◽  
Gene And Protein Expression ◽  
Pro Inflammatory Cytokines

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Mitigation of IL-1β, IL-6, TNF-α, and markers of apoptosis by ursolic acid against cisplatin-induced oxidative stress and nephrotoxicity in rats

2021 ◽  
Vol 40 (12_suppl) ◽  
pp. S397-S405
Author(s):  
Pankaj Tripathi ◽  
Saeed Alshahrani
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Histological Damage ◽  
Tnf Α ◽  
Mda Content ◽  
Pro Inflammatory Cytokines

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

scholarly journals Pharmacological activation of GPR55 improved cognitive impairment, neuroinflammation, oxidative stress and apoptosis induced by lipopolysaccharide in mice

2020 ◽  
Author(s):  
Xin Wang ◽  
Xiao Tong Xiang ◽  
Jie Hu ◽  
Yu Mei Wu ◽  
YueYue Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Sod Activity ◽  
Neuroprotective Effects ◽  
Impaired Performance ◽  
Pro Inflammatory Cytokines

Abstract BackgroundNeuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of Alzheimer’s disease (AD). The purpose of the present study was to investigate the neuroprotective effects and possible mechanism of G-protein coupled receptor 55 (GPR55) agonist, O-1602, on lipopolysaccharide (LPS)-induced cognitive deficits in mice. MethodsICR mice were treated with intracerebroventricular (i.c.v.) injection of LPS. Cognitive tests were performed, including the open field, Morris water maze, novel object recognition, and passive avoidance tests. The expression of GPR55, NF-κB p65, caspase-3, Bax and Bcl-2 were examined in the hippocampus by western blotting. Pro-inflammatory cytokines and microglia were detected by ELISA kit and immunohistochemical analyses, respectively. The malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were examined by assay kits. Furthermore, TUNEL-staining was used to detect neuronal apoptosis.ResultsI.c.v. injection of LPS exhibited impaired performance in the behavior tests, which were ameliorated by O-1602 treatment(2.0 or 4.0 μg/mouse, i.c.v.). Importantly, O-1602 reversed GPR55 down-regulation, decreased the expression of NF-κB p65, and suppressed the accumulation of pro-inflammatory cytokines and microglia activation, decreased malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity. In addition, O-1602 also significantly decreased Bax and increased Bcl-2 expression as well as decreased caspase-3 activity and TUNEL-positive cells, suppressed neuronal apoptosis in the hippocampus of LPS-treated mice.Conclusionswe conclude that O-1602 may ameliorate LPS-induced cognition deficits via inhibiting neuroinflammation, oxidative stress and apoptosis mediated by NF-κB signaling in mice.

Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines

Cytokine ◽  
2019 ◽  
Vol 113 ◽  
pp. 405-416 ◽  
Author(s):  
Adel A. Gomaa ◽  
Rania M. Makboul ◽  
Mohamed A. El-Mokhtar ◽  
Engy A. Abdel-Rahman ◽  
Israa A. Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Diabetic Rats ◽  
Elettaria Cardamomum ◽  
Pro Inflammatory Cytokines

scholarly journals Renoprotective Influence of Pomegranate Juice on Nephrotoxicity Induced by Methotrexate

2021 ◽  
pp. 103-113
Author(s):  
Afnan H. Saaty
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Antioxidant Property ◽  
Renal Tissue ◽  
Pomegranate Juice ◽  
Male Rats ◽  
High Dose ◽  
Rheumatic Arthritis ◽  
Renal Functions ◽  
Pro Inflammatory Cytokines

Methotrexate (Metho) is cytotoxic drug widely used to treat malignant (lymphoma, leukemia, breast cancer) and non-malignant (rheumatic arthritis) diseases. It mediates nephrotoxicity via cellular oxidative stress. Pomegranate juice (POJ) has a potent antioxidant property. This research aimed to assess the potential protective effect of POJ against Metho-induced renal damage in rats. Renal toxicity was induced through intraperitoneal (ip) injection with a single dose of Metho (20 mg/kg). Forty male rats were randomly segregated into 4 groups; each group contained 10 rats. Control (Cont); Metho: rats on the 23rd day injected ip with Metho; POJ (2 ml/kg) +Metho: rats given POJ (2 ml/kg) orally once a day, and on the 23th day injected with Metho ip; and POJ (4 ml/kg) + Metho: rats given POJ (4 ml/kg) orally once a day, and on the 23th day rats were injected with Metho ip. After 5 days of Metho ip. injection, blood samples and renal tissue were obtained. Serum renal functions, ionic electrolytes (sodium and potassium), and pro-inflammatory cytokines were analyzed. Renal oxidative stress and antioxidant enzymes were also measured. Renal tissue were examined microscopically. Metho caused a significant increase in serum renal functions and disturbance in ionic electrolytes. As well as, there was a significant increase in pro-inflammatory cytokines and oxidative stress parameters, with detectable degenerative alteration in glomerulus and renal tissue changes compared with the Cont group. Pretreatment with POJ resulted in preventing biochemical and histopathological alterations induced by Metho. The high dose of POJ (4 ml/kg) was significantly more effective than low dose (2 ml/kg). In conclusion, POJ exerted a potent nephroprotective action and prevent Metho-induced nephrotoxicity. Therefore, POJ may has a beneficial effect in patients receiving Metho therapy.

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