Ketotifen counteracts cisplatin-induced acute kidney injury in mice via targeting NF-κB/NLRP3/Caspase-1 and Bax/Bcl2/Caspase-3 signaling pathways.

Cisplatin (CIS) stands as one of the most effective chemotherapy drugs currently available. Despite its anticancer properties, the clinical application of CIS is restricted due to nephrotoxicity. Our research aimed to specify the impact of ketotifen fumarate (KET) against nephrotoxicity induced by CIS in mice. Male NMRI mice were treated with KET (0.4, 0.8, and 1.6 mg/kg, ip) for seven days. On the fourth day of the study, a single dose of CIS (13 mg/kg, ip) was administered, and the mice were sacrificed on the eighth day. The results indicated that administration of KET attenuated CIS-induced elevation of BUN and Cr in the serum, as well as renal KIM-1 levels. This improvement was accompanied by a significant reduction in kidney tissue damage, which was supported by histopathological examinations. Likewise, the decrease in the ratio of GSH to GSSG and antioxidant enzyme activities (CAT, SOD, and GPx), and the increase in lipid peroxidation marker (TBARS) were reversed in KET-treated mice. The ELISA results revealed that KET-treated mice ameliorated CIS-induced elevation in the renal levels of TNF-α, IL-1ß, and IL-18. Western blot analysis exhibited that KET suppressed the activation of the transcription factor NF-κB and the NLRP3 inflammasome in the kidney of CIS-treated mice. Moreover, KET treatment reversed the changes in the protein expression of markers related to apoptosis (Bax, Bcl2, Caspase-3, and p53). Interestingly, KET significantly enhanced the cytotoxicity of CIS in HeLa cells. In conclusion, this study provides valuable insights into the promising effects of KET in mitigating CIS-induced nephrotoxicity.

Dimethyl itaconate mitigates histological distortions, inflammation, and oxidative stress in the rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation and infertility in women. Inflammation and oxidative stress are considered to be the causes of ovarian dysfunction in PCOS. Dimethyl itaconate, as a macrophage-derived immunometabolite, has anti-inflammatory and antioxidative properties, but limited data are available about its effect on female reproductive dysfunctions. The present study aimed to determine the effects of dimethyl itaconate, a cell-permeable derivative of itaconate, on the histological changes, oxidative stress, and inflammation in the ovaries of PCOS rats. In this experimental study, 48 mature female Wistar rats (180-200g) were randomly divided into the six groups including control, PCOS, PCOS+DMI, PCOS+ metformin, control DMI and control metformin. Following PCOS induction by using testosterone enanthate (1mg/100g/day for 35 days), the animals were treated with DMI (50mg/kg) or metformin (300mg/kg) for 30 days. At the end of the experimental period, the insulin resistance markers (serum insulin and glucose concentrations, and the homeostasis model assessment of basal insulin resistance (HOMA-IR), oxidative stress index (OSI), and inflammatory cytokines were measured. The process of Folliculogenesis was evaluated by histological examination of the ovary. The results showed that DMI improved insulin resistance and decreased TNF- and IL-1ß levels and OSI in the ovarian tissue of rats following androgen-induced PCOS. It also improved steroidogenesis and Folliculogenesis by reducing cystic follicles and ovarian tissue structure. Results indicated that DMI may be a potential candidate to ameliorate PCOS adverse effects by reducing insulin resistance, inflammation, and oxidative stress and restoring ovarian Folliculogenesis.

Betaine Attenuates The Expression of Vasoactive Mediators and Histological Alterations Associated with Ovarian Hyperstimulation Syndrome in Rats.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model. MATERIALS AND METHODS: In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes. RESULTS: Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals. CONCLUSION: Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET.

Effects of Multi-species Synbiotic Supplementation on Circulating miR-27a, miR-33a Levels, and Lipid Parameters in Adult Men with Dyslipidemia; A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

MicroRNAs (miRNAs) have emerged as important regulators of lipid metabolism. Recent studies have suggested synbiotics may modulate miRNA expression and lipid metabolism. This study aimed to investigate the effects of synbiotic supplementation on circulating miR-27a, miR-33a, and lipid parameters in patients with dyslipidemia. Fifty-six eligible participants were randomly allocated to receive either synbiotic or placebo sachets twice a day for 12 weeks. Each synbiotic sachet contained 3×1010 CFU six species of probiotic microorganisms and 5 grams of inulin and fructooligosaccharide (FOS) as prebiotics. Serum miR-27a and miR-33a expression levels, serum lipids, and apolipoproteins, the fecal concentration of short-chain fatty acids (SCFAs), and Firmicutes and Bacteroidetes phyla were assessed before and after the study. Real-time PCR was used to determine the relative expression levels of miRNAs. The results showed synbiotic supplementation significantly downregulated the expression levels of miR-27a and miR-33a compared to the placebo group (p = 0.008 and p = 0.001, respectively). Furthermore, the intervention group exhibited significant improvements in serum high-density lipoprotein (HDL-C), small dense low-density lipoprotein (sdLDL-C), apoA-I, and apoB-100 (p = 0.008, p = 0.006, p = 0.003, p = 0.001, respectively). The results showed a significant negative correlation between miR-33a expression levels with HDL-C, butyrate, propionate, and a significant positive correlation with total cholesterol (TC), low-density lipoprotein (LDL-C), and sdLDL-C in the intervention group. Fecal bacteria and SCFAs were significantly increased in the intervention group. This study provides evidence that synbiotic supplementation can modulate miR-27a and miR-33a expression and improve lipid metabolism in patients with dyslipidemia.

Randomized clinical trial evaluating the efficacy of synbiotic supplementation on serum endotoxin and trimethylamine N-oxide levels in patients with dyslipidaemia.

Introduction: Elevated serum endotoxin and trimethylamine N-oxide (TMAO) are associated with metabolic disorders including dyslipidaemia and insulin resistance. This study aimed to evaluate the impact of a 12-week treatment with a synbiotic supplement on serum endotoxin and TMAO levels in patients diagnosed with dyslipidaemia. Material and methods: A total of 56 patients who met the study inclusion criteria were recruited in this randomized, double-blind clinical trial. Participants were randomly assigned into intervention and control groups and received either synbiotic or placebo sachets twice a day for 12 weeks. The sociodemographic data, food intake, physical activity, and anthropometric indices of participants were assessed before and after intervention. Serum endotoxin, TMAO, and fasting blood glucose (FBG) levels were measured at the baseline and end of the study. Results: No significant difference in the baseline characteristics of participants in the 2 groups was observed. After the 12 weeks of intervention, the mean of serum endotoxin (p < 0.0001), TMAO (p < 0.0001), and FBG (p < 0.0001) was decreased in patients who received synbiotic supplements while no significant change was observed in the control group. Moreover, a significant positive correlation between changes in endotoxin (r = 0.41, p = 0.041) and TMAO (r = 0.40, p = 0.047) with FBG changes was observed. Conclusions: A significant reduction in serum endotoxin and TMAO levels, as well as improvements in FBG, following 12 weeks of supplementation with synbiotics, may offer a potential approach for improving metabolic status in patients with dyslipidaemia.

Alpha-pinene ameliorate behavioral deficit induced by early postnatal hypoxia in the rat: study the inflammatory mechanism.

Neonatal hypoxia has a negative impact on the developing brain during the sensitive period. Inflammation plays a key role in the physiological response to hypoxic stress. Considering the anti-inflammatory properties of alpha-pinene, which has received a lot of attention in recent years, in this research we focused on the impact of alpha-pinene on the behavioral responses and proinflammatory factors in rats subjected to the neonatal hypoxia. This study involved Wistar rats (7-day-old) that were divided into six experimental groups, including a control group, groups receiving different doses of alpha-pinene (5 and 10 mg/kg), a hypoxia group receiving 7% O2 and 93% N2, 90 min duration for 7 days, and groups receiving alpha-pinene 30 min before hypoxia. All injections were done intraperitoneally. The rats were evaluated for proinflammatory factors 24 h after exposure to hypoxia (PND14) and at the end of the behavioral test (PND54). The results showed that hypoxia led to decreased motor activity, coordination, and memory, as well as increased inflammation. However, the rats that received alpha-pinene showed improved behavioral responses and reduced inflammation compared to the hypoxia group (all cases p < 0.05). This suggests that alpha-pinene may have a protective effect via anti-inflammatory properties against the negative impacts of hypoxia on the developing brain.

Fish oil ameliorates ethanol-induced gastric injury in rat by modulating gene related to apoptosis.

Gastric ulcers are a type of digestive disease that can severely affect a person's quality of life. Our study aimed to investigate the effects of fish oil on ethanol-induced gastric ulcers in rats, with the purpose of providing more comprehensive information on the topic. The study looked at various factors such as gastric ulcer index, and nitric oxide (NO) levels in stomach tissue. To investigate apoptosis, the mRNA levels of Bax, Bcl-2, and Caspase 3 were analyzed. The results showed that fish oil can reduce gastric acidity and the gastric ulcer index in cases of ethanol-induced gastric ulcers. It was found that fish oil can increase NO levels and improve the anti-apoptotic system by increasing the expression of Bcl-2 while decreasing the expression of Bax and Caspase 3. In general, the study demonstrates that fish oil can protect the stomach from ethanol-induced damage by reducing the apoptosis pathway via nitric oxide.

The influence of indole propionic acid on molecular markers of steroidogenesis, ER stress, and apoptosis in rat granulosa cells exposed to high glucose conditions.

Hyperglycemia is known as one of the main causes of infertility in human societies. Indole propionic acid (IPA) is produced by intestinal microbiota and has antioxidant and anti-inflammatory properties. This study aims to investigate the effects of IPA on molecular indices of steroidogenesis, ER stress, and apoptosis induced by high glucose (HG) in granulosa cells. Primary GCs, isolated from ovarian follicles of Rats were cultured in 5 mM (control) and 30 mM (HG) of glucose and in the presence of 10 and 20 µM of IPA for 24 h. The cell viability was assessed by MTT. The gene expression of P450SCC, 3ßHSD, CYP19A, BAX, BCL2, and STAR was evaluated by Real-Time PCR. Protein expression of ATF6, PERK, GRP78, and CHOP determined by western blot. Progesterone, estradiol, IL-1ß, and TNF-α were measured by ELISA. HG decreased the viability, and expression of P450SCC, 3ßHSD, CYP19A, BCL2, STAR, and increased BAX. 10 and 20 µM of IPA increased cell viability, expression of P450SCC, 3ßHSD, CYP19A, BCL2 and STAR and decreased BAX compared to the HG group. The expression of ATF6, PERK, GRP78, and CHOP proteins increased by HG and IPA decreased the expression of these proteins compared to the HG group. Also, HG decreased progesterone and estradiol levels and increased IL-1ß and TNF-α. IPA significantly increased progesterone and estradiol and decreased IL-1ß and TNF-α compared to the HG group. IPA can improve the side effects of HG in GCs of rats, as responsible cells for fertility, by improving steroidogenesis, regulation of ER-stress pathway, suppression of inflammation, and apoptosis.

The impact of Dimethyl itaconate on c-Fos expression in the spinal cord in experimental pain models.

Itaconate has been found to have potent anti-inflammatory effects and is being explored as a potential treatment for inflammatory diseases. However, its ability to relieve nociception and the mechanisms behind it are not yet understood. Our research aims to investigate the nociception-relieving properties of dimethyl itaconate (DMI) in the formalin test and writhing test. In male Wistar rats, Itaconic acid was injected intraperitoneally (i.p.). The formalin test and writhing test were conducted to determine the nociceptive behaviors. The spinal cords were removed from the rats and analyzed for c-fos protein expression. The study found that administering DMI 10 and 20 mg/kg reduced nociception in formalin and writhing tests. Injection of formalin into the periphery of the body led to an increase in the expression of c-fos in the spinal cord, which was alleviated by DMI 20 mg/kg. Similarly, acetic acid injection into the peritoneal cavity caused an increase in c-fos expression in the spinal cord, which was then reduced by 20 mg/kg. According to our findings, DMI reduced nociception in rats during the formalin and writhing tests. One possible explanation for this outcome is that the decrease in c-fos protein expression may be attributed to the presence of DMI.

Modulatory effects of quercetin on histological changes, biochemical and oxidative stress of rat placenta induced by inhalation exposure to crude oil vapor.

The inhalation exposure to crude oil vapor (COV) has been shown to have adverse effects on the placenta and fetal development. The modulatory effects of quercetin (QUE) as a natural phenolic compound with antioxidant properties are promising for the protection of placental structure. This study aimed to investigate the modulatory role of QUE in mitigating histopathological damage, oxidative stress, and biochemical alteration in the placenta of COV-exposed pregnant rats. Forty-eight pregnant rats were divided into eight groups (days 15 and 20) as follows: 1-2) Control groups, 3-4) COV groups, 5-6) COV+QUE groups, and 7-8) QUE-treated groups (50 mg/kg). The inhalation method was used to expose pregnant rats to COV, and QUE was administered orally. On the 15th and 20th days of gestation, placental tissue was analyzed using PAS and H&E staining and immunohistochemistry. The expression of the caspase-3 gene and oxidative stress biomarkers including TAC, CAT, MDA, GPx, and SOD were investigated in the placental tissue. The COV significantly decreased the weight, diameter, and thickness of the placenta as well as the thickness of the junctional zone and labyrinth and the number of trophoblast giant cells in 15- and 20-day-old placentas (P<0.05). Also, COV significantly increased placental expression of caspase-3 and the oxidative stress biomarkers (P<0.05). The administration of QUE along with exposure to COV reduced morphometric and histological alteration, oxidative stress, and caspase-3 expression (P<0.05). Our findings indicated that QUE in COV-exposed pregnant rats can prevent placental histopathological alternations by increasing the activity of the antioxidant system.

Insoluble fibre and enzyme supplementation in mash or pellets diets on growth performance, apparent ileal digestibility and intestinal morphology of broiler chickens fed barley containing diets.

BACKGROUND: Enzyme supplementation and the inclusion of fibre in the barley-based diets have been some of the alternatives proposed to improve productivity in the absence of growth promoters. OBJECTIVE: This study was performed to investigate the effect of adding sunflower hulls (SFH), a multi-enzyme carbohydrate, and feed forms (mash and pellet) on performance and some physiological parameters in broiler chickens fed barley containing diets. METHODS: Treatments were two feed forms (mash vs. pelleted), and four diets consisted of a barley-based diet (control, CTL) or test diets which contained either SFH at 30 g/kg, enzyme (ENZ; 0.2 g/kg) or combination of SFH and enzyme (SFH + ENZ). RESULTS: The results showed that average daily feed intake and average daily gain were significantly increased in chickens that were fed ENZ (p < 0.05). The highest digestibility of ether extract (EE) was observed in the treatment containing SFH and SFH + ENZ (p < 0.05). The highest population of Lactobacillus spp. was observed in the treatment containing SFH (p < 0.05). The villus height and villus height to crypt depth ratios of duodenum and jejunum were significantly higher (p < 0.05) in broilers fed pellet diets compared to the mash. CONCLUSION: It can be concluded that pellet diets reduce digesta viscosity and harmful microorganisms (Escherichia coli), increase growth performance, and improve intestinal morphology in barley-based diets. Moreover, SFH and ENZ had favourable effects on EE digestibility and caecal microbial population of broilers fed with barley containing diets.

Effective Inhibition of Listeria monocytogenes Biofilm Formation by Satureja rechingeri Essential Oil: Mechanisms and Implications.

Biofilm formation by foodborne pathogens, particularly Listeria monocytogenes, poses a significant challenge in food industry facilities. In this study, we investigated the inhibitory potential of Satureja rechingeri essential oil (Sr-EO) against L. monocytogenes growth and biofilm formation. Gas chromatography-mass spectrometry analysis revealed a high carvacrol content in Sr-EO, a compound with known antimicrobial properties. We examined the effects of Sr-EO on initial attachment and preformed biofilms, using crystal violet and MTT assays to quantify attached biomass and metabolic activity, respectively. Our results demonstrated that Sr-EO not only prevented initial attachment but also effectively disrupted preformed biofilms, indicating its potential as a biofilm-control agent. Microscopy analysis revealed alterations in bacterial cell membranes upon Sr-EO treatment, leading to increased permeability and cell death. Additionally, Sr-EO significantly suppressed bacterial motility, with concentrations exceeding 0.25 µL/mL completely inhibiting motility. Furthermore, gene expression analysis revealed the down regulation of genes associated with biofilm formation, attachment, and quorum sensing, suggesting that Sr-EO modulates bacterial gene transcription. These findings suggest that Sr-EO can be a promising candidate for controlling biofilm formation and bacterial contamination in food processing environments.

Betaine regulates steroidogenesis, endoplasmic reticulum stress response and Nrf2/HO-1 antioxidant pathways in mouse Leydig cells under hyperglycaemia condition.

We studied the effects of betaine on steroidogenesis, endoplasmic reticulum stress and Nrf2 antioxidant pathways of mice Leydig cells under hyperglycaemia conditions. Leydig cells were grown in low and high glucose concentrations (5 mM and 30 mM) in the presence of 5 mM of betaine for 24 h. Gene expression was determined using a real-time PCR method. The protein levels were determined by Western blot analysis. The testosterone production was evaluated by the ELISA method. Cellular contents of reduced and oxidised glutathione were measured by colorimetric method. Hyperglycaemia caused impaired steroidogenesis and ERS in Leydig cells associated with the down-regulation of 3ß-HSD, StAR, P450scc, LH receptor and increased expression of GRP78, CHOP, ATF6 and IRE1. Betaine could improve cell viability, attenuate the ERS, and restore testosterone production in Leydig cells under hyperglycaemia conditions. Betaine can protect Leydig cells against the adverse effects of hyperglycaemia by regulating steroidogenesis, antioxidants, and ERS.

Protective effect of quercetin on fetal development and congenital skeletal anomalies against exposure of pregnant Wistar rats to crude oil vapor.

BACKGROUND: Epidemiological evidence indicates a relationship between maternal exposure to crude oil vapors (COV) during pregnancy and adverse pregnancy outcomes. Quercetin (QUE) is a plant flavonoid with purported antioxidant and anti-inflammatory effects, which has been shown to prevent birth defects. This study was aimed to investigate the protective role of QUE on fetal development and congenital skeletal anomalies caused by exposure of pregnant rats to COV. METHODS: Twenty-four pregnant Wistar rats were randomly categorized into four groups of control, COV, COV + QUE, and QUE (50 mg/kg). The inhalation method was used to expose pregnant rats to COV from day 0 to 20 of pregnancy, and QUE was administered orally during this period. On day 20 of gestation, the animals were anesthetized and a laparotomy was performed, and then the weight and crown rump length (CRL) of the fetuses were determined. Skeletal stereomicroscopic evaluations of fetuses were performed using Alcian blue/Alizarin red staining method, and the expression of osteogenesis-related genes (Runx2 and BMP-4) was evaluated using qPCR. RESULTS: This study showed that prenatal exposure to COV significantly reduced fetal weight and CRL, and expression of Runx2 and BMP-4 genes. Moreover, COV significantly increased the incidence of congenital skeletal anomalies such as cleft palate, spina bifida and non-ossification of the fetal bones. However, administration of QUE with exposure to COV improved fetal bone development and reduced congenital skeletal anomalies. CONCLUSION: QUE can ameliorate the teratogenic effects of prenatal exposure to COV by increasing the expression of osteogenesis-related genes.

Prenatal exposure to crude oil vapor reduces differentiation potential of rat fetal mesenchymal stem cells by regulating ERK1/2 and PI3K signaling pathways: Protective effect of quercetin.

It has been indicated that crude oil vapor (COV) induces tissue damage by several molecular mechanisms. Quercetin (QT) as an important component of food with antioxidant properties has a protective role against cell toxicity caused by many pollutants. However, data related to the adverse effects of crude oil vapor (COV) on stem cell fate and differentiation and the role of quercetin (QT) in protecting stem cells against the toxicity caused by these pollutants is very limited. This study aimed to explore the protective effect of QT against the adverse effects of COV on fetal mesenchymal stem cells (fMSCs) differentiation. Twenty-four pregnant Wistar rats were categorized into 4 groups including the control, COV, COV+QT, and QT. Rats were exposed to COV from gestational day (GD) 0-15 and received QT by gavage. The fMSCs were isolated from fetuses, and cell proliferation, differentiation potential, expression of osteogenesis and adipogenesis-related genes, and phosphorylation of PI3K and ERK1/2 signaling proteins were evaluated. The results showed that COV reduced the proliferation and differentiation of fMSCs through the activation of PI3K and ERK1/2 signaling pathways. Also, COV significantly decreased the expression of osteonectin, ALP, BMP-6, Runx-2, PPARγ, and CREBBP genes in differentiated cells. QT treatment increased the proliferation and differentiation of fMSCs in COV-exposed rats. In conclusion, our findings suggest that prenatal exposure to COV impaired fMSCs differentiation and QT reduced the adverse effects of COV by regulating ERK1/2 and PI3K signaling pathways.

Corrigendum to: Betaine ameliorates high glucose-induced oxidative stress in granulosa cells.

CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis. AIMS: In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis. METHODS: Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay. KEY RESULTS: We observed significant (P NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P Conclusion: Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level. IMPLICATIONS: As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.

Betaine ameliorates high glucose-induced oxidative stress in granulosa cells.

CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis. AIMS: In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis. METHODS: Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay. KEY RESULTS: We observed significant (P <0.001) up-regulation of NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P <0.001) down-regulation of related antioxidant genes (Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P <0.001) elevation of malondialdehyde was observed. In addition, betaine treatment compensated the drastic effect of high glucose induced oxidative stress via down-regulating the expression of NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P <0.001) restored the oestradiol and progesterone level. CONCLUSION: Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level. IMPLICATIONS: As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.

Type 2 Diabetes Mellitus Coincident with Clinical and Subclinical Thyroid Dysfunctions Results in Dysregulation of Circulating Chemerin, Resistin and Visfatin.

The alterations of circulating adipocytokines have been reported in thyroid diseases or type 2 diabetes mellitus (T2DM), but such data in T2DM coincident with clinical and subclinical thyroid-dysfunctions are limited, and remain to be investigated. We studied the changes in serum chemerin, resisitin and visfatin in T2DM patients with thyroid dysfunctions, and their association with inflammatory and insulin resistance-markers. A total of 272 female and male Iranian participants were selected and divided into six groups: the euthyroid group, T2DM, T2DM coincident with clinical and sub clinical hypothyroidism (SC-HO, and C-HO), and T2DM coincident with clinical and sub clinical hyperthyroidism (SC-HR, C-HR).Demographic characteristics, serum levels of adipocytokines, thyroid hormones, inflammatory factors (IL1-ß, IL-6 and CRP) and insulin resistance-markers were determined in all participants. T2DM patients with clinical thyroid dysfunctions showed higher levels of circulating resistin, visfatin, chemerin and inflammatory factors, compared with the T2DM group and T2DM coexisted with subclinical thyroid diseases. No significant differences were observed in circulating adipocytokines and inflammatory markers between T2DM coexisting with subclinical thyroid diseases and those without thyroid dysfunctions. Our results revealed that clinical thyroid dysfunction in T2DM patients was associated with elevated levels of circulating resistin, chemerin, visfatin and inflammatory factors, while no such alteration was detected in T2DM coincident with subclinical thyroid dysfunction.

Effects of chemical and green nano-zinc oxide on histological changes, oxidative stress, and apoptosis in rat kidney associated with cisplatin

Abstract Cisplatin (CP) is used to treat various tumors. A main restriction of cisplatin is nephrotoxicity. This study aimed to evaluate the protective effects of ZnONPs on cisplatin-induced oxidative stress and rat kidney tissue damage. Eighty adult male Wistar rats (250g-270g) were divided into ten groups: Control (CON), Sham (SH), Bulk ZnO (BZnO), Chemical ZnONPs (ChZnONPs), Green ZnONPs (GrZnONPs), Cisplatin (CP), Cisplatin+BulkZnO (CP+BZnO), Cisplatin+Green ZnONPs (CP+GrZnONPs), Cisplatin+Chemical ZnONPs (CP+ChZnONPs), Cisplatin+Explant (CP+EX). CP was i.p administered 5mg/kg/week and BZnO, ChZnONPs and GrZnONPs were i.p administered at a dose of 5mg/kg/day. After 30 days of the treatment, the expression of apoptosis/anti apoptosis related genes oxidant/antioxidant factors and histological changes in the were studied. The CP-treated group showed a decrease in body weight, while the Co-administration of ZGNPs to CP-treated rats showed a significant increase compared to the CP group. The results showed that the increased mRNA level of bax, MDA and the decreased mRNA level of bcl2, SOD and CAT activities in kidney of CP group were improved when animals were treated with ZnO NPs. Our results showed that GrZnONPs, ChZnONPs and BZnO had the potential to protect against oxidative stress and cisplatin-induced neurotoxicity that this protective effect was more evident in GrZnONPs.

Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model.

OBJECTIVE: Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation ability and viability of stem cells, but little is known about the critical function of Itaconate on the stem cell fate. The objective of the present study was to determine the regulatory effects of Itaconic acid on the cell viability and transcription of apoptosis and autophagy pathways genes in the rat adipose derived mesenchymal stem cells (ADMSCs). MATERIALS AND METHODS: In this experimental study, the ADMSCs were incubated with 125 µM and 250 µM dimethyl itaconate (DMI) for 24 hours or 48 hours. The expression of apoptosis pathway genes (Bax, Bcl2, Caspase 3, Fas, Fadd and Caspase 8) and autophagy pathway genes (Atg12, Atg5, Beclin, Lc3b and P62) were determined using real time polymerase chain reaction (PCR) assay. Using the ELISA method, cellular level of phospho-NRF2 protein was measured. RESULTS: The results indicated that DMI increased the expression of NRF2 protein, altered the expression of some apoptosis genes (Fadd, Bax and Bcl2), and changed the expression of some autophagy related genes (Lc3b, Becline and P62) in ADMSCs. DMI had no obvious effect on the transcription of caspases enzymes. CONCLUSION: Because autophagy activation and apoptosis suppression can protect stem cells against environmental stress, it seems Itaconate can affect the functions and viability of ADMSCs via converse regulation of these pathways.