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Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed countries and is associated with the increased rates of chronic kidney disease (CKD). Statin therapy could reduce cholesterol synthesis as well as progression of CKD. Diversity between statins causes variety in pharmacokinetics and pharmacodynamics and also their pleiotropic effects. In the present investigation we aimed to evaluate the protective potentials of both atorvastatin (Ator) (as lipid-soluble statin) and rosuvastatin (Ros) (as water-soluble statin) against renal histopathological damages in the high cholesterol diet induced hypercholesterolemic rats (HCDIHR).Materials and Methods: Serum lipid profile, oxidized low density lipoprotein (OX-LDL), malondialdehyde (MDA), urea and creatinine levels, as well as renal histopathology were evaluated.Results: While Ros acted better than Ator to reduce serum low density lipoprotein cholesterol (LDL-C) (PConclusion: The findings underline that the lipophilic Ator may performs better than Ros in attenuating renal damages in HCDIHR.

Purpose: This study was aimed to evaluate the site-specific drug delivery of 5-FU with chitosan (CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. Methods: Cross-linked CS-Qu nanoparticles (NPs) were prepared by ionotropic gelation method. Physicochemical characterization of NPs was performed by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency (LE). 1, 2-Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induce adenocarcinoma tumors on inbred male Wistar rats’ colon. The treatment group of rats was administered through enema with NPs dispersion. Hematoxylin and eosin staining were performed to the histopathological examination of tumors. Results: Zeta potential and particle size for NPs were +53.5 ± 5 mV and 179 ± 28 nm, respectively. About 96% Qu LE was obtained with a maximum release of 5.63 ±1.59% and 4.62 ± 1.33% after 24 hours in PB solution with pH values of 6 and 7.4, respectively. The numbers of 8 to 21 tumors were observed in all rats administered with DMH and DSS. Significantly decreasing of microvascular density and mitosis count was detected in the treatment group in comparison with cancerous group (P = 0.032 for the former compared to P = 0.016 for the later), respectively. Furthermore, the treatment group showed a high apoptosis rate (P = 0.038). Conclusion: The developed Qu-loaded CS NPs were good candidates for site-specific and sustained drug release in enema treatment. Decreasing of microvascular density and mitosis count, along with increasing the apoptosis percent in the treatment group proved that the NPs could have promising results in site-specific and sustained drug delivery against colorectal cancer.

Objective(s): Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.Materials and Methods: Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.Results: In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.Conclusion: These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4.

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats.Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined.Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury.Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent.

Introduction: Systemic lupus erythematosus (SLE) is a relatively common disease among the patients referred to the rheumatology clinics. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), as a cytokine, is a member of TNF family, and CD160 is an essential natural killer (NK) cell activator, both of which have been argued to be associated with SLE activity. Here, we aimed to evaluate the serum levels of sTWEAK and CD160 and their association with SLE activity. Methods: In a descriptive cross-sectional study, 48 patients with SLE, as the case group, and 40 healthy subjects, as controls, were enrolled. SLE activity was assessed using SLE Disease Activity Index (SLEDAI) in the case group. Moreover, the serum levels of sTWEAK and CD160 were determined using enzyme linked immunosorbent assays (ELISA) method in both groups. Results: Mean serum level of sTWEAK was 19.09% lower in the control group compared to the case group (730.15 ± 170.21 pg/ml vs. 895.39 ± 451.25 pg/ml, respectively). Further, mean serum level of CD160 was 47.31% lower in the healthy subjects than that of SLE patients (206.16 ± 88.97 pg/ml vs 391.30 ± 283.46 pg/ml, respectively). The differences in both occasions were found to be significant (P = 0.013 and P =0.001, respectively). Mean SLEDAI in the patients was 8.68 ± 4.00. There was no significant correlation between serum levels of sTWEAK and CD160 with SLE activity. Conclusion: The serum levels of sTWEAK and CD160 markers in patients with SLE are significantly higher than those of healthy subjects. However, we found no correlation of these markers with the disease activity.

Background: Infertility is defined as the inability to achieve the pregnancy within a year of unprotected intercourse. Infertility is a complex issue and different factors such as stress oxidative can be involved in this problem. So, any attempt to neutralize oxidative stress would be helpful in the treatment of infertility. Melatonin is a known scavenger of free radicals. Objective: The aim of our study was to evaluate the level of melatonin and its correlation with oxidative biomarkers in fertile and infertile women. Materials and Methods: The participants including fertile and infertile women were divided into two groups of 30 people. Blood sampling was performed and sera were collected. The level of Malondialdehyde (MDA), total antioxidant capacity (TAC) and melatonin were detected. Data were analyzed using T-test and their correlation was assessed using Spearman test. Results: Serum melatonin from fertile women was higher than infertile women but the difference was not significant (p= 0.46). MDA level in fertile women was significantly lower than infertile women (p

Introduction: Infertility is the problem of 15% of young couples in different societies. One of the factors that could affect fertility is oxidative stress. Therefore, the aim of the present study is to investigate the level of Melatonin, a free radical scavenger, and its correlation with oxidative biomarkers in infertile men. Methods:For this purpose, fertile and infertile men in 2 groups, 30 people in each group, were studied. The fertile men were selected from husbands of patients admitted to Alzahra obstetric and gynecology hospital, according to WHO standards. The infertile men were selected from patients referred to infertility ward. Blood sampling from the participants carried out at a specific time, sera collected and the levels of malondialdehyde, total antioxidant capacity and Melatonin were detected in the sera. The data were analyzed using t-test and Sperman's correlation method. Results: Melatonin level in the sera from fertile men were 522 (39.32) ng/L and in infertile men were 511.78 (34.6) ng/L. MDA level in fertile and infertile men were 2.26 (0.34) vs 2.99 (0.44) nmol/ml which was significantly different. The level of TAC in the sera from fertile men were significantly higher than in infertile men. The result obtained for correlation coefficient Spearman's test revealed a significant, strong and direct correlation between Melatonin and TAC and a significant and reverse correlation between melatonin and MDA.Conclusion: It is concluded that melatonin could be involved in infertility. In other word, melatonin treatment and antioxidant-rich nutrition could help fertility by combating oxidative stress.