TAC Levels Research Articles

The PPAR-α agonist oleoyethanolamide (OEA) ameliorates valproic acid-induced steatohepatitis in rats via suppressing Wnt3a/β-catenin and activating PGC-1α: Involvement of network pharmacology and molecular docking.

Liver damage is one of the most severe side effects of valproic acid (VPA) therapy. Research indicates that PPAR-α prevents Wnt3a/β-catenin-induced PGC-1α dysregulation, which is linked to liver injury. Although PPAR-α activation has hepatoprotective effects, its role in preventing VPA-induced liver injury remains unclear. Our research used network analysis, molecular docking, and in-vivo validation to predict and assess targets and pathways associated with the hepatoprotective effects of oleoylethanolamide (OEA), a PPAR-α agonist, on VPA-induced steatohepatitis. For in-vivo experiments, 24 rats were assigned to V, OEA, VPA, and OEA+VPA. Liver functions, TGs, cholesterol, and LDL were tested. Hepatic levels of PPAR-α, ACO, TNF-α, IL-1β, HO-1, MDA, and TAC, along with Wnt3a/β-catenin, PGC-1α, and Nrf2 expression were assessed. Further, NF-κB, Bax, Bcl-2, and caspase-3 expression were detected immunohistochemically. Network pharmacology identified 258 targets for OEA-steatohepatitis connection, including NFKB1, PPARA, and NFE2L2, in addition to TNF, non-alcoholic fatty liver, NF-κB, PPAR, and WNT signaling, as contributing to steatohepatitis pathogenesis. The docking revealed a strong affinity between OEA and Wnt3a, β-catenin, and PGC-1α. Therefore, we postulated that the hepatoprotective effect of OEA may be due to Wnt3a/β-catenin-mediated inactivation of PGC1-α pathway. In vivo, OEA inhibited Wnt3a/β-catenin and increased PGC1-α by activating PPAR-α. Hence, PGC1-α reduced fat cell β-oxidation and NF-κB-mediated inflammation. OEA lessened MDA and raised TAC to mitigate oxidative damage. OEA additionally reduced apoptosis by lowering Bax/Bcl-2 ratio and caspase-3. In summary, PPAR-α involvement in the protective effects of OEA against VPA-induced steatohepatitis can be confirmed by suppressing Wnt3a/β-catenin and activating PGC-1α signaling.

Total Antioxidant and Oxidative Status as Potential Biomarkers of Alcohol Overdose.

Serious alcohol-associated hazards underscore the need to develop new biomarkers reflecting the biological changes caused by chronic alcohol use and predicting the risk of alcohol-related death. Oxidative stress is one mechanism of alcohol toxicity. The blood and urine redox status (total antioxidant capacity [TAC], total oxidative status [TOS], and oxidative stress index [OSI]) was assessed in 105 people who died a sudden death (controls), 47 people who died of alcohol overdose, and 102 people with alcohol dependency. TAC and TOS were determined utilizing the colorimetric method. Non-parametric tests were used for statistical analysis. Blood and urine TAC levels were significantly elevated in individuals both with alcohol dependency and alcohol poisoning compared with controls. TOS levels were elevated in the blood of both study groups compared with the control group, and significantly higher in patients with alcohol dependency compared with the group with alcohol poisoning. TAC in the blood highly correlated with blood alcohol content. Receiver operating characteristic (ROC) analysis showed that the blood TAC effectively discriminated between individuals with alcohol poisoning and alcohol dependency with high sensitivity and specificity. Our study confirmed impaired redox homeostasis in people with alcoholism and indicated the utility of TAC, TOS, and OSI as biomarkers of alcohol exposure.

Acyclovir provides protection against 6-OHDA-induced neurotoxicity in SH-SY5Y cells through the kynurenine pathway

Parkinson's disease is one of the most prevalent neurodegenerative disorders worldwide. The kynurenine pathway associated with oxidative stress and neuroinflammation is recognized to contribute to its pathophysiology, although the exact mechanism is not fully elucidated. In neuroinflammation, IDO-1 catalyzes the conversion of tryptophan to neurotoxic QUIN through the kynurenine pathway. Consequently, QUIN increases oxidative stress via nNOS and NMDA, which causes neurodegeneration. Few studies have reported on the effect of different antiviral drugs in Parkinson's disease; the exact mechanism is still unknown. The antiviral acyclovir has been shown to have neuroprotective properties and can cross the blood-brain barrier. We examined acyclovir's effects and potential mechanisms in the 6-OHDA-induced in vitro model of Parkinson's disease in SH-SY5Y cells using biochemical, immunocytochemical, and in silico methods. MTT assay demonstrated that acyclovir significantly decreased cell mortality induced by the neurotoxic 6-OHDA at dosages of 3.2 µM, 6.4 µM, 12.8 µM, 25.6 µM, and 51.2 µM. In immunocytochemical analysis, acyclovir treatment decreased α-synuclein and TNF-α expressions in cells. In biochemical analyses, while IL-17A and TOS levels decreased depending on varying doses (1.6 µM, 3.2 µM, 6.4 µM, 12.8 µM), TAC levels increased. Using in silico analyses to investigate the mechanism showed that acyclovir docked with TNF-α, IL-17A, IDO-1, nNOS, α-synuclein, and NMDA. The findings demonstrated that acyclovir had neuroprotective effects by modulating the kynurenine pathway and decreasing neurodegeneration via QUIN inhibition in an in vitro Parkinson's disease model. Although the mechanisms of acyclovir's effects in Parkinson's disease are unclear, the results obtained from the experiments are encouraging.

A double-edged sword effect of silver nanoparticles on angiogenesis in 4T1 breast cancer-bearing mice.

Silver nanoparticles (AgNPs) are increasingly known to have anticancer effects, but few studies have examined their adverse effects, so the underlying mechanisms are not yet fully understood. The current study investigated the critical influence of AgNPs on angiogenesis in 4T1 breast cancer-bearing mice. The sub-lethal dose of AgNPs (0.25mg/kg) was carried out. Female BALB/c mice (N = 35) were divided into 7 groups; normal control, cancer control, AgNPs control (one dose of (0.25mg/kg) AgNPs), single dose AgNPs before cancer, single dose AgNPs after cancer, 5 doses AgNPs after cancer, and doxorubicin. 4T1 breast cancer cell induction was performed subcutaneously on the left flank. Intraperitoneal (IP) administration of AgNPs and doxorubicin was carried out for all studied groups. Weight gain was normal in all study groups except the doxorubicin-treated group. Administering AgNPs before cancer induction promotes tumorigenesis, raises MMP-2 and MMP-9 activity, and increases CD31 and Ki67 expression. The cancer control group experienced the same outcomes. On the other hand, depending on the administered doses, the injection of AgNPs after tumor induction resulted in a notable decrease in tumor volume.In the doxorubicin-treated group, similar results were observed, while a dose of AgNPs‌ before cancer induction lead to increasing tumor volume compared to the cancer control group. The differences of biochemical markers including LDH, ALP, AST, ALT, BUN, and Cr between different groups were not significant. Significant differences were seen among all studied groups except doxorubicin and single dose AgNPs before cancer groups for serum TAC levels. It appears that AgNPs are considered a double-edged sword in the fight against cancer. AgNPs not only have anti-cancer effects on tumor size and angiogenesis, but they also might have cancer-stimulating roles. To confirm this conclusion, more detailed investigations are needed.

Chlorogenic acid improves urogenital dysfunction induced by exposure to ambient particulate matter.

Oxidative stress is a well-known underlying mechanism for several diseases in response to environmental pollution. Although there is a lack of evidence on the relationship between air pollution and an established risk factor for urogenital dysfunction. The aim of this study was to investigate the mechanism of particulate matter (PM) on urogenital function and evaluate the potential efficacy of chlorogenic acid (CGA) in preventing urogenital damage in rats. Forty Wistar rats were divided into five groups (n = 8): control, particulate matter exposure (animals were exposed to fine dust in an inhalation chamber for 4 weeks, 3 days a week, for 3 h, PM10 concentration adjusted to 500-2000 µg/m3), and particulate matter plus 3 concentrations of chlorogenic acid (100, 200, and 400 mg/kg, gavage, 4 weeks, 3 days a week). At the end of the study, kidney biomarkers, oxidative stress markers, antioxidant enzymes, the oxidation resistance 1 (OXR1) and its downstream gene expression, sperm count, gonadotropin hormones, and the structure of the kidney, epididymis, and seminal vesicle were evaluated in response to PM exposure and CGA treatment in all groups. The data obtained from the current study showed that PM exposure led to kidney dysfunction and inhibition of oligospermia through oxidative stress, as evidenced by an increase in MDA and a decrease in TAC, SOD, CAT, and GSH concentration levels in blood samples. These results were consistent with the down-regulation of OXR1, Nrf2, and P21 gene expression. In contrast, CGA improved urogenital biomarkers and histopathology structures of the kidney, epididymis, and seminal vesicle by enhancing antioxidant defense system enzymes and modulating the OXR1 signaling pathway. Our findings suggest that environmental air pollution contributes to kidney dysfunction and urogenital damage. Modulation of oxidative stress through the OXR1, P21, and Nrf2 signaling pathways may be the underlying mechanism. Furthermore, chlorogenic acid supplementation could be recommended as a new protective or treatment strategy to safeguard urogenital function against exposure to particulate matter.

Effects of quercetin-immobilized albumin cerium oxide nanoparticles on glutamate toxicity: in vitro study.

One aspect of glutamate (Glut) toxicity may be the opening of the blood-brain barrier to albumin (Al), which in itself can cause nerve cell death. Quercetin (Q) is a polyphenolic substance and has a neuroprotective effect. Cerium oxide nanoparticles (Ce2O3NPs) are highly interested in biological applications due to their antioxidant properties. The current study aimed to investigate the impact of Q-immobilized Al+Ce2O3NPs in Glut-induced neurotoxicity, mainly focusing on cell viability and neurobiochemical changes. Hydrothermal synthesis and characterization of Q-immobilized Al+Ce2O3NPs were performed. After preparing the primary neuron culture, it was exposed to Glut to induce neurotoxicity. Then, various doses of Ce2O3NP, Al+Ce2O3NP, and Q+Al+Ce2O3NPs (1, 5, 10, and 25 µg/ml) were applied to the wells and incubated for 24 h. Then, cell viability was determined by MTT analysis. Additionally, oxidative stress parameters were measured. When the obtained data were examined, it was shown that cell viability decreased with Glut concentration but significantly increased with Q+Al+Ce2O3NPs treatment. When oxidative stress markers were considered, Glut treatment increased LDH, AChE, and TOS levels, while TAC and GSH levels decreased. However, the trend changed after Q+Al+Ce2O3NPs treatment, suggesting that damaged neurons were protected against oxidative stress. The results of this study indicate that Q+Al+Ce2O3NP can ameliorate Glut-induced neurotoxicity, especially when used at a dose of 25 µg/ml.

Protective effects of berberine against diabetes-associated cognitive decline in mice.

Diabetes associated cognitive decline (DACD) is a common CNS-related consequence of diabetes. The primary clinical manifestation of DACD includes learning and memory impairment. Unfortunately, there is no cure to delay the cognitive symptoms of diabetes. Although berberine (BBR) has shown promising effect in the treating diabetes and cognitive dysfunction, more research is needed to understand the mechanism of its therapeutic effect. For better understanding, we investigated the functions of BBR involved in anti-inflammation, anti-oxidant and neuroprotection in the hippocampus of diabetic mice. Diabetes was induced in mice using STZ. BBR was administered for 4 weeks before (pre-treatment), and after (post-treatment) STZ administration. The effect of BBR on cognitive functions in diabetic mice was determined using neurobehavioural test. Moreover, how BBR affected neuroinflammation, oxidative stress, and acetylcholine levels in the hippocampus and BBB permeability were analyzed using standard biochemical assays. Lastly, we evaluated the mRNA expression of neuroprotective genes in the hippocampus to uncover the mechanism of BBR. Treatment with BBR improved cognition in diabetic mice. It significantly reduced the levels of IL-6, iNOS, TNF-α, IL-1β, ROS and MDA and increased the levels of TAC, GSH, SOD and Catalase. Moreover, levels of acetylcholine and BBB permeability were reduced in the diabetic mice which was reversed by BBR treatment and increased the expression of IGF and BDNF in the hippocampus of diabetic mice. Our results suggest that BBR might be a potential therapeutic candidate for the treatment of DACD. Our study might serve as a basis for developing novel drugs for treating DACD.

Cardiomodulating Activity of Gongronema latifolium and Lisinopril in Doxorubicin-induced Cardiotoxicity in Wistar Rats

Background: A major side effect of some cancer drugs, including Doxorubicin, is cardiotoxicity. This study was designed to evaluate the cardioprotective role of ethanolic leaf extract of Gongronema latifolium (GL) compared to Lisinopril in doxorubicin-induced cardiotoxicity in rats. Methods: Forty Wistar rats of both sexes (150-200 g) were divided into 5 groups (n=8 each). Group 1 (control) took normal rat chow; Group 2 received 25 mg/kg Doxorubicin; Group 3 received Doxorubicin + GL (200 mg/kg orally); Group 4 received Doxorubicin + Lisinopril (10 mg/kg orally); and Group 5 received Doxorubicin + Lisinopril + GL. The regiment lasted for 28 days. Blood samples were collected from each animal via cardiac puncture for biochemical assays. Results: The results of the study showed a significant decrease in superoxide dismutase (SOD) concentration in the doxorubicin group as compared to the control group. Intervention with GL and Lisilopril caused a significant increase in SOD concentration. Total antioxidant capacity, catalase, SOD, and angiotensin-II levels were significantly decreased with a corresponding increase in malondialdehyde (MDA) in the Doxorubicin group. Treatment with GL and Lisinopril significantly reversed these changes by increasing the levels of TAC, SOD, CAT, and angiotensin-2 to normal while lowering the MDA levels to normal. Cardiac biomarkers, namely troponin and creatine kinase levels, were significantly increased in the doxorubicin group as compared to the normal control. However, the coadministration of GL and Lisinopril decreased the troponin and creatine kinase concentrations to normal levels. Conclusions: Gongronema Latifolium and Lisinopril provided better cardioprotective and antioxidant effects versus other agents against cardiotoxicity induced by Doxorubicin.

The ameliorating effects of adipose-derived stromal vascular fraction cells on blue light-induced rat retinal injury via modulation of TLR4 signaling, apoptosis, and glial cell activity.

Blue light (BL)-induced retinal injury has become a very common problem due to over exposure to blue light-emitting sources. This study aimed to investigate the possible ameliorating impact of stromal vascular fraction cells (SVFCs) on BL-induced retinal injury. Forty male albino rats were randomly allocated into four groups. The control group rats were kept in 12-h light/12-h dark. Rats of SVFC-control as the control group, but rats were intravenously injected once by SVFCs. Rats of both the BL-group and BL-SVFC group were exposed to BL for 2 weeks; then rats of the BL-SVFC group were intravenously injected once by SVFCs. Following the BL exposure, rats were kept for 8 weeks. Physical and physiological studies were performed; then retinal tissues were collected for biochemical and histological studies. The BL-group showed physical and physiological changes indicating affection of the visual function. Biochemical marker assessment showed a significant increase in MDA, TLR4 and MYD88 tissue levels with a significant decrease in TAC levels. Histological and ultrastructural assessment showed disruption of the normal histological architecture with retinal pigment epithelium, photoreceptors, and ganglion cell deterioration. A significant increase in NF-κB, caspase-3, and GFAP immunoreactivity was also detected. BL-SVFC group showed a significant improvement in physical, physiological, and biochemical parameters. Retinal tissues revealed amelioration of retinal structural and ultrastructural deterioration and a significant decrease in NF-κB and caspase-3 immunoreactivity with a significant increase in GFAP immunoreaction. This study concluded that SVFCs could ameliorate the BL-induced retinal injury through TLR-4/MYD-88/NF-κB signaling inhibition, regenerative, anti-oxidative, and anti-apoptotic effects.

Kallistatin and Glypican-3 as Reliable Biomarkers for the Prediction of Liver Cirrhosis

Background: Cirrhosis is a condition in which the liver does not function properly due to long-term damage, this damage is characterized by the replacement of normal liver tissue by scar tissue. Objective: In the present study, an attempt was made to explore the role of kallistatin (KAL) and glypican3 (GPC3) as a predictor of liver cirrhosis (LC) in patients with hepatitis, non-alcoholic fatty acid and autoimmune diseases. Materials and Methods: This case–control study included 98 cirrhotic patients (34 patients with hepatitis B & A, 31 patients with non-alcoholic fatty liver disease and 33 patients with autoimmune) and 30 apparently healthy individuals. The laboratory investigations were performed, and the serum KAL and GPC3 were measured in all volunteers. Results: Serum levels of KAL, GPC3, and TAC were significantly decreased and MDA increased (p<0.01) in patients with LC as compared to control. The significant difference can also be indicatly seen in patients with hepatitis > non-alcoholic fatty acid > autoimmune diseases, respectively. The area under the curve (AUC) results obtained indicate that Kal and GPC3 could potentially be used as greater predictive biomarkers in LC with hepatitis ˃ NAFLD ˃ autoimmune diseases (Kal: AUC= -0.97, -0.91, -0.88; Gyp3: AUC= 0.89, 0.84, 0.79, respectively). Conclusion: Incorporating KAL and GPC3 screening into routine check-ups for patients with hepatitis, non-alcoholic fatty liver, and autoimmune diseases could aid in the early detection and prevention of LC-associated complications.

Clinical trial of the effects of postbiotic supplementation on inflammation, oxidative stress, and clinical outcomes in patients with CVA

Background Cerebrovascular accidents (CVAs), or strokes, are major global health concerns associated with oxidative stress, inflammation, and gastrointestinal complications. This study aimed to explore the impact of postbiotic supplementation in CVA patients, specifically in terms of oxidative stress, inflammation, and clinical outcomes, as an alternative to probiotics with potential advantages. Method A prospective, single-center, randomized, controlled trial was conducted with 120 CVA patients in Iran. These patients were admitted to the ICU to assess the severity of their strokes. Patients were randomly assigned to receive either postbiotic supplementation (n = 60) or a placebo (n = 60). Various biomarkers related to oxidative stress, inflammation, and clinical outcomes were assessed. Data on demographic characteristics, nosocomial infections, and laboratory measurements were collected. Gut microbiota analysis was also performed on fecal samples. Results After the 7-day intervention, postbiotic supplementation resulted in significant improvements in inflammatory markers, oxidative stress, and a reduced incidence of pneumonia compared with those in the control group, with the postbiotic group demonstrating notable decreases in the serum IL-1β levels (-1.79; 95% CI: = -2.9 to -0.64, p = 0.002 ), MDA levels (-30.5; 95% CI: -54.8 to -6.1, p = 0.015), Hs-CRP levels (-0.67; 95% CI:-1.1 to -0.26 mg/dl, p = 0.001) and TAC levels (62.5; 95%CI: 34.1 to 90.9, p < 0.001) compared with those in the placebo group. However, no significant differences in other clinical outcomes, including the NIHSS score, NUTRIC score, and APACHE II score, or the gut microbiota profile, were observed between the two groups. Conclusion Postbiotic supplementation improved the levels of inflammatory factors and oxidative stress markers and reduced the risk of pneumonia in CVA patients. Trial registration This trial is registered in the Iranian Registry of Clinical Trials (registration code IRCT20180712040438N7), Registration date 06122022.

Use of Nuclear Factor of Activated T Cell-Regulated Gene Expression for Monitoring Immunosuppression with Extended-Release Tacrolimus after Liver Transplantation-A Proof of Concept.

There is a narrow therapeutic window for immunosuppression using calcineurin inhibitors. Drug trough levels do not reflect immunosuppression and should be replaced by pharmacodynamic monitoring. This prospective cohort study was designed to evaluate the effect of an extended-release formulation of tacrolimus (LCP Tac) on the nuclear factor of activated T cell-regulated gene expression (NFAT-RGE). The expression of interleukin-2, interferon-γ, granulocyte-macrophage colony-stimulating factor, and three reference genes was measured. Samples from 23 patients at defined time points in the first year after liver transplantation were analyzed using a droplet digital polymerase chain reaction. All samples were within the targeted trough levels of LCP Tac, and their LCP Tac peak levels and residual NFAT-RGE showed a strong inverse correlation (r = -0.8). Most importantly, there was an individual immunosuppressive response to the LCP Tac. The mean individual trough effect of LCP Tac on the three target genes when all time points were pooled was 33% (26-56%) in patients without infection and 81% (53-95%) in those with infection (p < 0.011). The mean individual peak effect was 48% (44-64%) in patients without infection and 91% (90-94%) in those with infection (p < 0.001). Thus, tailored immunosuppression based on residual NFAT-RGE could prevent infections associated with over-immunosuppression early after liver transplantation.

Tacrolimus Therapy Among Steroid-Resistant Nephrotic Syndrome Children: A Preliminary Study in West Java, Indonesia

Objective: To explore the outcomes of Tac therapy for Steroid-Resistant Nephrotic Syndrome (SRNS) and its implication in reducing the number of CKD events.Methods: An open, prospective, cohort study was conducted at a tertiary hospital in Bandung, West Java, Indonesia. Children (age 1–18 years old) with steroid and cyclophosphamide resistant nephrotic syndrome were enrolled in this study. Blood pressure, urinary protein, serum ureum, and creatinine levels were measured every month, Tac and soluble urokinase plasminogen activator receptor (supaR) levels were assessed at the 0, third, and sixth months.Results: Ten of fifteen subjects enrolled in this study got better within 3–6 months with a trend of decreasing suPAR level and proteinuria, as well as stable blood pressure and serum creatinine and ureum level. During treatment, no side effects of the subjects were found with the Tac level maintain safely.Conclusion: Tac is an effective and safe agent in treating SRNS, especially for those do not respond well to an alkylating agent.

Evaluation of antioxidant status of lens epithelial cells in cataract patients.

The main factor that causes cataracts is the increased oxidative stress and imbalance of an antioxidant defense mechanism, which leads to significant changes in the lens microarchitecture. Senile cataract is the most common type of acquired cataracts due to aging. We carried out a case-control study in the biochemistry department to examine the antioxidant status (catalase and total antioxidant capacity [TAC]) and lipid peroxidation marker, that is, malondialdehyde (MDA) in human lens epithelial cells (HLECs) of different grades of senile cortical, nuclear, and posterior subcapsular cataracts. We collected 150 samples from patients aged 50-90 years. These included 50 samples of cortical cataracts, 50 of nuclear cataracts, and 50 samples of posterior subcapsular cataracts. We measured catalase activity by the Beer method, TAC by the Benzie and Strain method, and protein by the Bradford method. We also estimated TAC in the aqueous extract of HLECs by the ferric reducing ability of plasma (FRAP) method and MDA by the thiobarbituric acid assay method. The results of this study showed that the level of catalase enzyme was higher in the first grade of nuclear, posterior subcapsular, and cortical cataracts than in other grades. This suggests that the catalase enzyme activity drops sharply in the second and third grades of these types of cataracts. The same pattern was observed for TAC, which was higher in the first grade of nuclear, posterior subcapsular, and cortical cataracts than in other grades. There were significant differences between catalase and TAC in different grades of cataracts, indicating that as the grading increases, both catalase and TAC decrease. The results of this study showed that the levels of MDA were higher and the levels of catalase and TAC were lower in patients with more severe cataracts compared to the healthy controls.

Nigella sativa oil mitigate paraquat-induced neurobehavioural, oxidative and histological alterations in the cerebellum of adult male wistar rat

Over the past few decades, several cases of poisoning and death resulting from environmental exposure to the herbicide, paraquat (PQ), has been reported. However, nigella sativa oil, with several antioxidants and anti-inflammatory properties present a significant tool against PQ-induced toxicity. Thus, the study aim was to assess the possible mitigative effect of nigella sativa oil administration on paraquat-induced neurotoxicity in the cerebellum. Twenty-eight (28) adult Wistar rats were randomly divided into four groups of seven (7) rats each. Group I (control) received 0.3ml of normal saline daily; Group II received 0.1ml of paraquat daily; Group III received 0.1ml of paraquat and 0.3ml of nigella sativa daily; and Group IV received 0.3ml of nigella sativa daily. Administrations were done via oral gavage and experimentation lasted for 14 days. On day 13 of the experiment, animals from all groups were subjected to neurobehavioral tests using hanging wire test for grip period. Afterwards, the rats were sacrificed using anesthesia. Blood samples was collected and the brains were harvested for biochemical and histological studies. The result from this study revealed a decrease in grip time in the hanging wire test, in the group administered PQ only when compared to the control. However, the groups administered nigella sativa oil (NSO) showed an increase in grip time compared to the PQ only treated group, these differences are however insignificant. Also, a marked decrease in the GST and TAC levels were observed in the group exposed to PQ only when compared to the control group. However, the groups treated with NSO showed marked increase in these antioxidants level compared to the PQ group. Also, however insignificant, PQ exposure caused a slight increase in ROS levels compared to the control, and slight decrease in ROS levels in the PQ+NSO and NSO respectively was recorded. Distortion in the histoarchitecture of the cerebellum, were also recorded in the PQ-treated group when compared to the control. However, preservation of general histoarchitecture was observed in these brain regions in the treatment groups. Keywords: Sativia Oil, Experiment, Wire Test.

Regulatory effects of vitamin E nano-emulsion on blood metabolites, immunological variables, testicular architecture, and sperm ultrastructure of heat-stressed V-line rabbit bucks

The study investigated the beneficial effects of vitamin E-loaded nano-emulsion (NEVE) on hemato-biochemical changes, oxidative stress, inflammatory responses, immunological variables, and semen quality in heat-stressed rabbit bucks. Forty adult V-line rabbit bucks were randomly assigned to four groups and fed diets containing NEVE at 0 (NEVE0), 50 (NEVE50), 100 (NEVE100), and 200 (NEVE200) mg/kg for 12 weeks. The NEVE had a mean particle diameter of 32.6 nm, a polydispersity index of 0.6, and a zeta potential of −31.1 mV. The dietary NEVE significantly improved the hematological, blood protein, lipid profile, and liver functions of rabbit bucks (p < 0.05). The NEVE200 treated group showed higher levels of nitric oxide, TAC, and SOD in blood serum and seminal plasma compared to the control group (p < 0.05). Meanwhile, levels of MDA, IL-4, and TNF-α were significantly shrunken in response to the dietary treatment (p < 0.0001), while the IgA and IgG were improved in the NEVE100 and NEVE200 groups. The NEVE200 exhibited higher progressive motility, ejaculate volume, viability, and better libido (lower reaction time) than the untreated group (p < 0.05). TEM images illustrated that NEVE200 exhibited higher sperm cells with a normal structure, intact plasma membranes, and acrosomes than the other groups. Moreover, testicular architecture was improved with NEVE supplementation. Overall, the dietary addition of NEVE at 100 or 200 mg/kg could be an effective strategy to improve the health and semen quality of rabbit bucks during hot climates.

Using Urine Biomarkers to Differentiate Bladder Dysfunctions in Women with Sensory Bladder Disorders.

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner's interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management.

Effects of Ellagic Acid Supplementation on Antioxidant Status and Symptom Improvement in Patients with Major Depressive Disorder: A Double-blind Randomized Clinical Trial

Background: Depression is one of the most common mood disorders and a major public health concern. Ellagic acid (EA), a type of polyphenol, acts as a strong hydrogen bond network as an electron receptor, enabling it to participate in various reactions. Objectives: Major depression is a critical medical condition that has emerged as a public health issue due to its high incidence, mortality, and suicide rates. One significant factor in the pathogenesis of depression is oxidative stress. This study aimed to evaluate the effects of ellagic acid supplementation on antioxidant status and symptom improvement in patients with major depressive disorder, considering the antioxidant capabilities of ellagic acid. Methods: A total of 40 patients diagnosed with major depressive disorder based on DSM-V criteria were assessed using the Beck Depression and Hamilton Depression Questionnaires. The dietary and caloric intake of the patients were monitored. Additionally, height and weight were measured, and patients with similar age, gender, and weight were matched. The individuals were randomly assigned to either the intervention group or the placebo group using a randomization table. The intervention group received a daily dose of 200 mg of ellagic acid in capsule form. The placebo group received a daily dose of one capsule containing 200 mg of wheat flour, identical in appearance to the intervention substance. The study period lasted for 8 weeks. Venous blood samples were collected before and after the study from all 40 individuals, and after serum separation, oxidative stress markers (malondialdehyde and total antioxidant capacity). were measured using a specific kit and ELISA method. Results: The study results showed a significant reduction in depression scores in the ellagic acid group during the study (P: 0.001)., with these alterations being significant when compared to the placebo group. In the ellagic acid group, a significant increase in total antioxidant capacity (P: 0.027). and a significant decrease in malondialdehyde levels (P: 0.014). were observed at the end of the study, and these changes were significant compared to the placebo group. In contrast, significant changes in total antioxidant capacity and malondialdehyde levels were not observed in the placebo group. Conclusions: The current study indicates that ellagic acid intervention may have a favorable effect on depression in patients with major depressive disorder. This is achieved by reducing BDI scores and serum levels of MDA, as well as increasing serum levels of TAC in these patients compared to the placebo group. However, further investigation is necessary to explore the mechanisms underlying the different alterations of ellagic acid in depression.

Pattern of CYP3A5 and MDR-1 single nucleotide polymorphism and its impact on Tacrolimus levels and clinical outcomes in living renal allograft recipient

Abstract Introduction Renal transplant is best form of renal replacement therapy. Most favored immunosuppression includes Tacrolimus, mycophenolate mofetil and steroids. Tacrolimus has narrow therapeutic index and requires therapeutic drug monitoring (TDM). However, there is wide variation in tacrolimus level with weight based fixed dosage regimens. This variability is due to polymorphism of major pathways of metabolism ie CYP3A5 and MDR1 genes. Fast metabolizer require higher dosage and slow metabolizer require lower dosage. Genotype based dosing strategy may be useful to achieve early therapeutic level and reduce infections and rejections. Methodology 160 transplant patients at tertiary care hospital in India were included in this study from 2016 to 2018. Genetic polymorphism analysis in CYP3A5 and MDR1 gene was carried out at time of transplant. All patients were given a fixed weight-based dosage of Tacrolimus. Data was analyzed in relation to genotype polymorphism. Results and discussion 69.2% of Wild variants of CYP 3A5 (Fast metabolizers) have low initial tacrolimus levels. 51.5% of Homo variants (Slow metabolizers) have high initial tac levels. However, all variants achieve optimum tacrolimus levels at same time (mean 12.4 days). There were higher number of infections among slow metabolizers. Conclusion A fixed dosing regimen with TDM result in high and low initial tacrolimus levels in slow and fast metabolizers respectively and more infections in slow metabolizers. However, graft rejections being fewer in number, were not different. A larger sample with genotype based dosing is required to test such a strategy.

#601 Overweight-obese kidney transplant recipients have altered tacrolimus clearance and need lower doses for target levels with good graft outcomes

Abstract Background and Aims CYP3A4 which has been associated with altered tacrolimus (Tac) clearance. Clearances for drugs that are CYP3A4 substrates are generally reduced by 10%-35% in obese compared to normal-weight individuals. This study assessed the early and late Tac levels and weight-based total daily dose (TDD) for target Tac level in overweight-obese kidney transplant (KT) recipients and its relation to graft outcomes. Methods A retrospective study included 62 live-related KT recipients: overweight-obese KT recipients (N=32) with body mass index (BMI) &amp;gt;25 and normal-weight KT recipients (N=30) with BMI &amp;lt;25. The Tac level and weight-based TDD were examined in the 1st 3 months and 1 year after kidney transplantation with assessment of graft outcome. Results The overweight-obese patients' mean BMI was 31.29 and normal-weight patients' mean BMI was 22.20 p-value (0.0001). There was no significant difference between overweight-obese patients and normal-weight patients in mean Tac levels in 1st 3 months and after 1-year (mean 8.902, 6.99 ng/ml versus 8.906, 6.91 ng/ml respectively) p-values (0.992, 0.850) respectively. The weight-based TDD for target Tac level in 1st 3 months and after 1-year was significantly lower in overweight-obese than normal-weight patients (mean 0.108, 0.073 ng/ml versus 0.167, 0.102 ng/ml) respectively with p-value (0. 00035, 0.0076) respectively. KT recipients with BMI &amp;gt;30 showed lower weight-based TDD versus KT recipients with BMI 25-30 in 1st 3 months (0.094 versus 0.131 ng/ml) p-value (0.0255) while no difference after 1-year p-value (0.353). Graft outcomes did not significantly differ between overweight-obese versus normal-weight patients; the mean serum creatinine (1.22 versus 1.27 mg/dl) p-value (0.680) and graft rejection was (6 patients versus 6 patients) p-value (0.104) without graft loss. The weight-based TDD after 1-year was negatively correlated with BMI and transplant duration {r −0.369, p 0.003, r −0.278, p 0.028} respectively. Conclusion Overweight-obese patients have altered Tac clearance and they need lower doses to achieve target Tac level in the early and late periods post-transplant which is linked to good graft outcomes. According to these preliminary data the department is planning to study the effect of CYP 3A4/5 genetic polymorphisms on Tac dose requirement in most of these patients.