Protective Effect of Curcumin and Nanocurcumin on Sperm Parameters and Oxidant-antioxidants System of Rat Testis in Aluminium Phosphide Subacute Poisoning.

OBJECTIVE: Aluminum phosphide (AlP) as an effective pesticide may contribute to oxidative stress and adversely influence sperm parameters. This study aimed to investigate the protective role of curcumin and nanocurcumin on oxidative damage in the testis of rats with AlP toxicity. METHODS: A total of 42 adult male Wistar rats were equally randomized into the following study groups (n = 7): Control, Control+Curcumin, Control+Nanocurcumin, AlP, AlP+Curcumin, and AlP+Nanocurcumin. The testis tissue was used to investigate the levels of testicular malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and reduced glutathione (GSH) as well as the Catalase (CAT) and superoxide dismutase (SOD) enzyme activity. Epididymal sperm was used to perform sperm analysis. RESULTS: AlP administration led to a significant increase in MDA, and TOS levels and also markedly decreased the SOD activity and the levels of TAC and GSH in testis tissue (p <0.001). Moreover, the motility and viability of sperms were significantly reduced (p <0.001). Curcumin and Nanocurcumin co-administration with AlP remarkably decreased the MDA and TOS level (p <0.001) and significantly increased the GSH and TAC levels as well as the activity of SOD in AlP intoxicated groups (p<0.001). Our findings demonstrated that Nanocurcumin administration has significantly enhanced the sperm quality in AlP intoxicated rats as compared to the control group (p <0.001). CONCLUSION: According to the results of this study, Curcumin as a potential antioxidant could be an effective attenuative agent against AlP-induced oxidative damage in testis, especially when it is used in encapsulated form, nanocurcumin.

Increased circulating level of CTRP15 in patients with type 2 diabetes mellitus and its relation with inflammation and insulin resistance.

AIMS: Type 2 diabetes mellitus (T2DM) is a highly prevalence disease that has a close relation with secretory factors such as adipokines and myokines. C1q tumor necrosis factor-α (TNF-α)-related protein 15 (CTRP15) is a paralogue paralogue of adiponectin that has a close relation with insulin resistance and inflammation. The present study aimed to assess circulating levels of CTRP15 in patients with T2DM in comparison with controls and thier association with inflammatory cytokines. METHODS: This case-control study was performed on 80 T2DM patients and 80 controls which diagnosed according to the criteria of American Diabetes Association (ADA). Serum levels of CTRP15, adiponectin, TNF-α, and interleukin- 6 (IL-6) were determined using ELISA kits. RESULTS: The results indicated higher concentration of CTRP15 in T2DM patients (103.17 ± 27.99) compared to the controls (66.11 ± 20.46, p < 0.001), while adiponectin decreased considerably in the patients compared to the controls (p < 0.001). Moreover, circulating levels of IL-6 and TNF-α elevated in the patients compared to the controls (p < 0.001). CTRP15 indicated independent association with BMI and adiponectin in the controls while, in the patients it demonstrated independent association with HOMA-IR and TNF-α. CONCLUSIONS: Higher concentration of CTRP15 in the patients and its relation with insulin resistance and inflammation suggested a relation of CTRP15 with the pathogenesis of diabetes. In addition, it seems likely that patients with T2DM had a CTRP15 resistance; however, future studies are necessary to prove this concept.

Imbalance in thioredoxin system activates NLRP3 inflammasome pathway in epicardial adipose tissue of patients with coronary artery disease.

Atherosclerosis is the leading cause of death worldwide and has in part an inflammatory basis. Since epicardial adipose tissue (EAT) is in close contact with coronary arteries we hypothesized that an imbalance in thioredoxin-1 (TRX-1) and thioredoxin interacting protein (TXNIP) in EAT, activates NLRP3 inflammasome and promotes production of IL-1ß, leading to the development of atherosclerosis. Thirty-eight patients with coronary artery disease (CAD) and thirty patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as CAD and control groups, respectively. Biopsy samples from EAT were collected and expression of TXNIP, TRX-1, NLRP3 and IL-1ß genes were assessed using qRT-PCR. Tissue protein levels of TXNIP and TRX-1 were determined by Western blotting while ELISA was applied to measure IL-1ß. Haematoxylin and eosin staining was used for histological examination. mRNA and protein levels of TXNIP in EAT were significantly higher in patients with CAD compared with control group, whereas CAD patients showed lower TRX-1 gene and protein expression. In addition, in CAD patients the NLRP3 gene expression was almost doubled and IL-1ß significantly increased at the both mRNA and protein levels. Enhancment in NLRP3 gene expression and TXNIP protein levels were accompanied with the increase in IL-1ß protein level whereas TRX-1 protein content showed a negative correlation with IL-1ß level. Concurrent increase in TXNIP, NLRP3, and IL-1ß suggests possible involvement of thioredoxin system in the activation of NLRP3 inflammasome, production of IL-1ß, and the presence of inflammation in CAD patients.

Effects of post-training administration of LY341495, as an mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet.

High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD (for 10 weeks) by using Morris Water Maze (MWM) task. The training session for testing memory acquisition in MWM consisted of 4 trials per day for 4 consecutive days. Twenty-four hours after the last training session the spatial probe test (retention) was given. Intraperitoneal injection (i.p) injection of LY341495 was done 30 min before probe test. Our results showed that 10 weeks consumption of HFD had no significant effect on escape latency and swimming distance in memory acquisition. Our finding showed that consumption of a HFD leads to reference memory impairment in the probe test. HFD animals spent less time in the target zone in compare with control animals. Also, LY341495 improved HFD-induced reference memory (retention) impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals. Escape latencies to find the visible platform during visual task were same in all experimental groups, indicating no visual impairment in the animals. We propose that a HFD may act through mGluR2/3 within the brain to reduce synaptic plasticity, which impairs memory retrieval, and post-training administration of LY341495 can reduce HFD-induced reference memory impairment.

Chronic NaHS treatment improves spatial and passive avoidance learning and memory and anxiety-like behavior and decreases oxidative stress in rats fed with a high-fat diet.

Cognitive function is impaired by increased consumption of a high-fat diet (HFD). Also, HFD consumption can alter hydrogen sulfide (H2S) metabolism. H2S is an important signaling molecule with antioxidant effects that regulates multiple functions in the brain. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, an H2S donor) on cognitive impairment and oxidative stress changes induced by HFD consumption. Following 11 weeks of HFD regimes in Wistar rats, elevated plus-maze (EPM), Morris water maze (MWM), and passive avoidance learning (PAL) tasks were used to evaluate the anxiety-like behavior and spatial and passive learning and memory, respectively. Daily intraperitoneal injection of NaHS was done during the dietary regimen. Serum and hippocampal oxidative stress biomarkers (malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS)) were measured. We demonstrated that treatment with NaHS ameliorated the impairment in the retrieval of reference memory and passive avoidance learning. Moreover, HFD increased anxiety-like behavior, which was reversed by the administration of NaHS. Additionally, the increase in MDA and TOS and the decrease in TAC induced by HFD in the serum and hippocampus were significantly reduced following administration of NaHS. These results indicate that NaHS could significantly ameliorate HFD-induced spatial and passive learning and memory impairment and anxiety-like behavior, at least in part, via its antioxidant activities. Therefore, the administration of NaHS can provide a therapeutic approach for HFD-induced memory impairment.

Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease.

Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted adipokine that regulates lipid metabolism and is associated with cardiometabolic diseases, including type 2 diabetes and CAD. However, the association between circulating ANGPTL8 levels and CAD is inconsistent among studies and the mechanism by which ANGPTL8 contributes to CAD development remains poorly understood. Here we sought to evaluate the relationship between ANGPTL8 levels and endothelial dysfunction and adipose tissue inflammation in CAD patients. Concentrations of ANGPTL8, adiponectin, TNF-α, IL6, hsCRP, ICAM-1, and VCAM-1 were measured by ELISA in serum samples from 192 CAD patients diagnosed with stenosis > 50% in at least one coronary artery by angiography and 71 individuals with normal heart function. Serum ANGPTL8 levels were significantly higher in CAD patients compared to controls (83.84 ± 23.25 ng/mL vs. 50.45 ± 17.73; p < 0.001), independent of adjustment for age, sex, BMI, smoking and statin use. ANGPTL8 could also differentiate CAD patients from controls with 82.3% specificity and 81.4% sensitivity (p < 0.001). Adiponectin levels were lower in CAD patients, while ICAM-1, VCAM-1, TNF-α, IL6, and hsCRP levels were higher compared to non-CAD controls (all p < 0.001). ANGPTL8 levels were associated with BMI in controls and with BMI, TG, and ICAM-1 in CAD patients. The presence of elevated ANGPTL8 levels in CAD patients and independent association with TG and ICAM-1 suggest a possible role related to endothelial dysfunction in the pathogenesis of atherosclerosis.

Tempol improves oxidant/antioxidant parameters in testicular tissues of diabetic rats.

AIMS: Oxidative stress induced by diabetes mellitus (DM) is considered as one of the main causes of infertility in diabetic patients. The aim of the present study was to assess the effect of Tempol - as a synthetic antioxidant- on the testis oxidative stress and sperm parameters in type 2 diabetic (T2D) rats. MAIN METHODS: Twenty male Wistar rats were divided into 4 groups. Control groups (C) and diabetic groups (D); the control and diabetic groups received Tempol (100 mg/kg) for one month. Sperm parameters and oxidative stress biomarkers were evaluated in testicular tissue. KEY FINDINGS: The results demonstrated that administration of Tempol in diabetic rats improved sperm motility and viability and decreased the count of abnormal sperms. Also Tempol decreased the fasting blood sugar (FBS) and lipid peroxidation (LPO). In addition, Tempol significantly increased total antioxidant capacity (TAC) levels in testis tissue of T2D rats. Histopathological changes were also improved in the diabetic treated group. SIGNIFICANCE: Taken together, the results indicated that Tempol improved fertility parameters in a diabetic rat through reducing oxidative stress.

Protective effect of cerium oxide nanoparticle on sperm quality and oxidative damage in malathion-induced testicular toxicity in rats: An experimental study.

BACKGROUND: Malathion is an organophosphorus pesticide that commonly used in many agricultural and non-agricultural processes. Previous studies have reported the effects of melatonin on the reproductive system. Cerium dioxide nanoparticles (CeNPs) due to their antioxidative properties are promising to impact on the development of male infertility. OBJECTIVE: The aim of this study was to evaluate the effect of CeNPs on oxidative stress and sperm parameters after malathion exposure of male rats. MATERIALS AND METHODS: 36 adult male Wistar rats were divided into 6 groups (n=6/each): Control, CeNPs -treated control (15 and 30 mg/kg/day), malathion (100 mg/ kg/day), and CeNPs -treated malathion groups (15 and 30 mg/ kg/day). At the end of the study (4 wk), the sperm counts, motility, and viability in the testis of rats were measured, also lipid peroxidation, total antioxidant capacity, and total thiol groups in homogenate testis were investigated. RESULTS: Malathion significantly reduced sperm count, viability, and motility than the control rats (p<0.001). Co-treatment of malathion with CeNPs 30 mg/kg had a protective effect on sperm counts (p=0.03), motility (p=0.01), and viability (p<0.001) compare to malathion group. Also, the results showed that malathion reduced testis total anti-oxidant capacity, the total thiol group, and increased testis malondialdehyde than the control rats (p<0.001). CeNPs 30 mg/kg are increased total antioxidant capacity (p<0.001) and total thiol group (p=0.03) compared to malathion group. CeNPs at both doses (15 and 30 mg/kg) improved malondialdehyde than the malathion group (p<0.001 and p=0.01 respectively). CONCLUSION: CeNPs 30 mg/kg administered considerably restored testicular changes induced by malathion. The improvement of oxidative stress by CeNPs may be associated with increased sperm counts, motility and viability in the testis.

Circulating Levels of IL-35 and Gene Expression of FoxP3 in Coronary Artery Disease: Is There Any Interplay Between Them and 25-Hydroxyvitamin D3?

BACKGROUND: We aimed to evaluate interleukin-35 (IL-35) serum levels and the forkhead box P3 (FoxP3) expression in peripheral blood mononuclear cells (PBMCs) of coronary artery disease (CAD) patients compared with the non-CAD group. Also, we examined the possible relationship between gene expression of FoxP3 and serum levels of IL-35 with several CAD-related clinical parameters. METHODS: This study was conducted on 40 men with CAD and 40 men with a normal coronary artery. The gene expression of FoxP3 was measured by real-time polymerase chain reaction (real-time PCR). The serum concentrations of IL-35 and 25-hydroxyvitamin D3 (25(OH)D3) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FoxP3 gene expression was significantly decreased in patients compared to controls (p = 0.01). Serum concentrations of IL-35 and 25(OH)D3 were significantly reduced in patients in comparison with the control group (both, p < 0.001), and reduction of IL-35 showed an independent association with CAD. IL-35 levels had a significant positive correlation with serum 25(OH)D3 (r = 0.266, p = 0.044) in the whole population. Moreover, there was an inverse correlation between the FoxP3 expression and CAD severity in CAD patients (r = -0.372, p = 0.01). CONCLUSIONS: It appears that reduced mRNA expression of FoxP3 and circulating level of IL-35 are of significance in the context of CAD pathogenesis. However, more studies are required to elucidate underlying mechanisms.

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

BACKGROUND: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients. METHODS: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). NPC1 gene expression analysis was performed by quantitative real-time PCR, and correlation between the two parameters was assessed. RESULTS: Mean IL-10 serum concentration and peripheral blood mononuclear cells' (PBMCs) gene expression of NPC1, adjusted for drug consumption, age, and BMI, was not significantly different between the patient and control groups (p = 0.6 and 0.67 respectively). However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29). We also observed lower serum concentration of IL-10 in the subjects with lower 25-hydroxyvitamin D serum concentration (p = 0.034). CONCLUSIONS: Our findings supported the previous observations showing the contribution of lysosomal lipid homeostasis of PBMCs to inflammation and pathogenesis of atherosclerosis.