Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

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Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine—a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-039358 ◽

2021 ◽

Vol 11 (1) ◽

pp. e039358

Author(s):

Suhairul Sazali ◽

Salziyan Badrin ◽

Mohd Noor Norhayati ◽

Nur Suhaila Idris

Keyword(s):

Random Effects ◽

Coenzyme Q10 ◽

Migraine Headache ◽

Meta Analysis ◽

Adult Patients ◽

Control Group ◽

Cochrane Central Register ◽

Statistical Heterogeneity ◽

Coq10 Supplementation ◽

The Impact

ObjectiveTo determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine.DesignSystematic review and meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, CENTRAL, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO) from inception till December 2019.Study selectionAll randomised control trials comparing CoQ10 with placebo or used as an adjunct treatment included in this meta-analysis. Cross-over designs and controlled clinical trials were excluded.Data synthesisHeterogeneity at face value by comparing populations, settings, interventions and outcomes were measured and statistical heterogeneity was assessed by means of the I2 statistic. The treatment effect for dichotomous outcomes were using risk ratios and risk difference, and for continuous outcomes, mean differences (MDs) or standardised mean difference; both with 95% CIs were used. Subgroup analyses were carried out for dosage of CoQ10 and if CoQ10 combined with another supplementation. Sensitivity analysis was used to investigate the impact risk of bias for sequence generation and allocation concealment of included studies.ResultsSix studies with a total of 371 participants were included in the meta-analysis. There is no statistically significant reduction in severity of migraine headache with CoQ10 supplementation. CoQ10 supplementation reduced the duration of headache attacks compared with the control group (MD: −0.19; 95% CI: −0.27 to −0.11; random effects; I2 statistic=0%; p<0.00001). CoQ10 usage reduced the frequency of migraine headache compared with the control group (MD: −1.52; 95% CI: −2.40 to −0.65; random effects; I2 statistic=0%; p<0.001).ConclusionCoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.PROSPERO registration numberCRD42019126127.

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Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

Infection and Immunity ◽

10.1128/iai.68.6.3153-3157.2000 ◽

2000 ◽

Vol 68 (6) ◽

pp. 3153-3157 ◽

Cited By ~ 47

Author(s):

Christian Østergaard ◽

Runa Vavia Yieng-Kow ◽

Thomas Benfield ◽

Niels Frimodt-Møller ◽

Frank Espersen ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Pneumococcal Meningitis ◽

Interleukin 1 ◽

Treated Group ◽

Control Group ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Significant Difference ◽

The Brain ◽

Experimental Pneumococcal Meningitis

ABSTRACT The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ∼106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively;P < 0.02). A less consistent decrease in CSF TNF-α levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively;P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-α into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

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Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0267 ◽

2018 ◽

Vol 44 (4) ◽

pp. 530-538

Author(s):

Aysun Çetin ◽

İhsan Çetin ◽

Semih Yılmaz ◽

Ahmet Şen ◽

Göktuğ Savaş ◽

...

Keyword(s):

Oxidative Stress ◽

Interleukin 1 ◽

Paraoxonase 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phenotypic Effect ◽

Necrosis Factor Alpha ◽

Stress Markers ◽

Tnf Α ◽

Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

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Postnatal distribution of ZnO nanoparticles to the breast milk through oral route and their risk assessment for breastfed rat offsprings

Human & Experimental Toxicology ◽

10.1177/0960327120921441 ◽

2020 ◽

Vol 39 (10) ◽

pp. 1318-1332

Author(s):

A Hussain ◽

S Kumar ◽

G Kaul

Keyword(s):

Zinc Oxide ◽

Breast Milk ◽

Interleukin 1 ◽

Immunoglobulin A ◽

Safety Evaluation ◽

Oral Route ◽

Control Group ◽

Spleen Weight ◽

Zno Nps ◽

Necrosis Factor Alpha

Various studies in rodents have shown that nanoparticles are transferred to the breast milk. Under the present study, lactating Wistar rats were repetitively gavaged 5, 25, and 50 mg/kg bw of zinc oxide nanoparticles (ZnO-NPs) and 50 mg kg−1 bw of bulk zinc oxide (bZnO) for 19 days after parturition. The results showed that ZnO-NPs were absorbed in the small intestine of dams and distributed to the liver. Furthermore, ZnO-NPs were distributed to the intestine and liver of rat pups through dam’s milk. No significant change in body weight was observed in the dams treated with ZnO-NPs or bZnO and their offsprings as compared to the control group. The spleen weight significantly increased in the rat dams treated with 50 mg kg−1 of ZnO-NPs. ZnO-NPs were mostly excreted through feces. The levels of liver cytochrome P450 reductase and serum total antioxidant capacity significantly decreased in the rat dams treated with ZnO-NPs (50 mg kg−1) and their offsprings. The levels of serum cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and liver injury marker enzymes (alanine aminotransferase and aspartate aminotransferase) significantly increased in the rat dams treated with ZnO-NPs (25 and 50 mg kg−1) and their offsprings. The level of immunoglobulin A secretion in the intestinal fluid of rat dams and their offsprings is significantly increased by increasing the dose of ZnO-NPs. Histopathology of intestine and liver of offsprings whose rat dams were treated with ZnO-NPs (50 mg kg−1) showed gross pathological changes. These results provide information for the safety evaluation of ZnO-NPs use during lactation. In conclusion, a dose-dependent postnatal transfer of ZnO-NPs is hazardous to the breastfed offsprings.

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Suppression of Tumorigenesis: Modulation of Inflammatory Cytokines by Oral Administration of Microencapsulated Probiotic Yogurt Formulation

International Journal of Inflammation ◽

10.4061/2010/894972 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Aleksandra Malgorzata Urbanska ◽

Arghya Paul ◽

Jasmine Bhahena ◽

Satya Prakash

Keyword(s):

Treatment Group ◽

Intestinal Inflammation ◽

Interleukin 1 ◽

Control Group ◽

Necrosis Factor Alpha ◽

Western Blots ◽

Reactive Protein ◽

Probiotic Yogurt ◽

Factor Alpha ◽

Irritable Bowel

The objective of this study was to examine the ability of a novel microencapsulated probiotic yogurt formulation to suppress the intestinal inflammation. We assessed its anticancer activity by screening interleukin-1, 6, and 12 (IL-1, 6, 12), secretory levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), prostaglandinE2 (PGE2), and thromboxane B2 in the digesta obtained from the duodenum, jejunum, proximal, and distal segments of the ileum of C57BL/6J-ApcMin/J mice. Formulation-receiving animals showed consistently lower proinflammatory cytokines' levels when compared to control group animals receiving empty alginate-poly-L-lysine-alginate (APA) microcapsules suspended in saline. The concentrations of IL-12 found in serum in control and treatment group animals were significant:46.58±16.96 pg/mL and158.58±28.56 pg/mL for control and treatment animals, respectively. We determined a significant change in plasma C-reactive protein:81.04±23.73 ng/mL in control group and64.21±16.64 ng/mL in treatment group. Western blots showed a 71% downregulation of cyclooxygenase-2 (COX-2) protein in treatment group animals compared to control. These results point to the possibility of using this yogurt formulation in anticancer therapies, in addition to chronic gut diseases such as Crohn's disease, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) thanks to its inflammation lowering properties.

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Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

Antioxidants ◽

10.3390/antiox9010010 ◽

2019 ◽

Vol 9 (1) ◽

pp. 10 ◽

Cited By ~ 19

Author(s):

Wafa A. AL-Megrin ◽

Afrah F. Alkhuriji ◽

Al Omar S. Yousef ◽

Dina M. Metwally ◽

Ola A. Habotta ◽

...

Keyword(s):

Nitric Oxide ◽

Lead Acetate ◽

Interleukin 1 ◽

Treated Group ◽

Control Group ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Toxic Heavy Metal ◽

Anti Inflammatory

The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

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Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.2.308 ◽

1997 ◽

Vol 41 (2) ◽

pp. 308-313 ◽

Cited By ~ 27

Author(s):

T Matsumoto ◽

K Tateda ◽

S Miyazaki ◽

N Furuya ◽

A Ohno ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Survival Rate ◽

Protective Effect ◽

Specific Activity ◽

Bacterial Colonization ◽

Interleukin 1 ◽

Protective Mechanism ◽

Protective Effects ◽

Bacterial Clearance ◽

Necrosis Factor Alpha

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

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The acquisition of an insulin-secreting phenotype by HGF-treated rat pancreatic ductal cells (ARIP) is associated with the development of susceptibility to cytokine-induced apoptosis

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01595 ◽

2005 ◽

Vol 34 (2) ◽

pp. 367-376 ◽

Cited By ~ 7

Author(s):

E Anastasi ◽

C Santangelo ◽

A Bulotta ◽

F Dotta ◽

B Argenti ◽

...

Keyword(s):

Type 1 Diabetes ◽

Beta Cell ◽

Pancreatic Beta Cells ◽

Interleukin 1 ◽

Pancreatic Beta Cell ◽

Necrosis Factor Alpha ◽

Ductal Cells ◽

Pancreatic Ductal Cells ◽

Induced Apoptosis

The elucidation of mechanisms regulating the regeneration and survival of pancreatic beta cells has fundamental implications in the cell therapy of type 1 diabetes. The present study had the following three aims: 1. to investigate whether pancreatic ductal epithelial cells can be induced to differentiate into insulin-producing cells by exposing them to hepatocyte growth factor (HGF); 2. to characterize some of the molecular events leading to their differentiation toward a beta-cell-like phenotype; 3. to evaluate the susceptibility of newly differentiated insulin-secreting cells to cytokine-induced apoptosis, a mechanism of beta-cell destruction occurring in type 1 diabetes. We demonstrated that HGF-treated rat pancreatic ductal cell line (ARIP) cells acquired the capability to transcribe the insulin gene and translate its counterpart protein. HGF-treated cells also exhibited a glucose-dependent capability to secrete insulin into the cultured medium. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent transcription of neurogenin-3 and Neuro-D in response to HGF. Finally, we determined the susceptibility to proinflammatory cytokine (PTh1)-induced apoptosis by incubating HGF-treated and untreated ARIP cells with a cocktail of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Such treatment induced apoptotic death, as determined by the TUNEL technique, in about 40% of HGF-treated, insulin-secreting ARIP cells, while untreated ARIP cells were resistant to PTh1-induced apoptosis. In conclusion, we showed that HGF promotes the differentiation of ARIP cells into pancreatic beta-cell-like cells, and that the differentiation toward an insulin-secreting phenotype is associated with the appearance of susceptibility to cytokine-induced apoptosis.

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Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence

Mediators of Inflammation ◽

10.1155/2017/9632846 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Arduino A. Mangoni ◽

Angelo Zinellu ◽

Salvatore Sotgia ◽

Ciriaco Carru ◽

Matteo Piga ◽

...

Keyword(s):

Rheumatic Disease ◽

Vascular Inflammation ◽

Interleukin 1 ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Disease States ◽

Autoimmune Rheumatic Disease ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Meta Analyses

There is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this patient group disrupts the structural and functional integrity of the endothelium and the arterial wall, favouring the onset and progression of atherosclerosis. A significant role in the detrimental effects of inflammation on endothelial function and vascular homeostasis is played by specific proatherosclerotic cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Recent systematic reviews and meta-analyses have shown that treatment with methotrexate, a first-line disease-modifying antirheumatic drug (DMARD), is associated with a significant reduction in atherosclerosis-mediated cardiovascular events, such as myocardial infarction and stroke, and mortality, when compared to other DMARDs. This suggests that methotrexate might exert specific protective effects against vascular inflammation and atherosclerosis in the context of autoimmune rheumatic disease. This review discusses the available evidence regarding the potential antiatherosclerotic effects of methotrexate through the inhibition of TNF-α, IL-1, and IL-6 and provides suggestions for future experimental and human studies addressing this issue.

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Microstructural changes and immunohistological analysis of pro-inflammatory cytokines in spleens of lipopolysaccharide-induced rats

Indian Journal of Animal Research ◽

10.18805/ijar.b-897 ◽

2018 ◽

Author(s):

Y. B. Zhong ◽

X. L. Zhang ◽

M. Y. Lv ◽

X. F. Hu ◽

Y. Li

Keyword(s):

Inflammatory Cytokines ◽

Optical Density ◽

Normal Saline ◽

Interleukin 1 ◽

Saline Group ◽

Control Group ◽

Sprague Dawley ◽

Necrosis Factor Alpha ◽

Lymphoid Follicles ◽

Pro Inflammatory Cytokines

This study investigated splenic status changes in weaned Sprague-Dawley rats induced by lipopolysaccharide. There were forty 26-day-old rats selected randomly and equally divided into two groups. The treatment group received daily single doses of lipopolysaccharide, and the control group was treated with normal saline. We conducted haematoxylin-eosin staining, immunohistochemical staining and semi-quantitative optical density analysis for both groups on the 29th, 32nd, 35th and 38th days after treatment. The results indicated that splenic marginal zone in the lipopolysaccharide group was thinner or disappeared compared to that of the saline group. However, the periarterial lymphoid sheath and the diameters of splenic lymphoid follicles appeared thicker and wider than those in the saline group (P less than 0.05). The expression of interleukin-1 beta, interleukin-6 and tumour necrosis factor alpha was mainly localized within the periarterial lymphoid sheath and splenic lymphoid follicles in the lipopolysaccharide treated rats. The integrated optical density and the average optical density in the lipopolysaccharide group were greater than those in the normal saline treated group (P less than 0.05). In conclusion, splenic immune function is probably strengthened by altering microstructures and releasing pro-inflammatory cytokines following lipopolysaccharide treatment.

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