Assessment of tear inflammatory cytokines concentration in patients with diabetes with varying severity of involvement.

Diabetic retinopathy (DR), as one of the most important causes of blindness in Western societies, is a common micro-vasculopathy associated with diabetes. There is growing evidence of the role of inflammation in its development. This study was designed to measure cytokines in patients with diabetes with different stages of retinopathy .In this study, tear concentrations of three types of cytokines with different angiogenic properties including IL-1RA, IL-8, and TNF-α were measured in patients with diabetes without retinopathy, with non-proliferative retinopathy, with proliferative retinopathy, and in a healthy control group. The results showed that concentrations of TNF-α and IL-8 were higher in the tear sample of diabetics than in the control group and the concentrations of these cytokines were higher in patients with more advanced stages of diabetes, while the tear level of IL-1RA was significantly lower in diabetics. Based on these findings, it can be concluded that diabetes and its progression of severity affects the tear levels of IL-1RA, IL-8, and TNF-α inflammatory cytokines.

S100 Calcium-Binding Protein B and Glial Fibrillary Acidic Protein in Patients with Mild Traumatic Brain Injury.

OBJECTIVE: To examine the GFAP and S100B ability in prevention unnecessary brain Computed tomography (CT) scan in mild traumatic brain injury (mTBI) and compare them with the single extremity fracture in orthopedic patients. METHODS: In this prospective cohort study, two orthopedics patients' groups and mTBI patients were studied to assess the biomarkers' ability in prevention unnecessary brain CT scan at the emergency setting. There were 40 orthopedics' patients with single extremity fracture and 41 mTBI patients. Brain CT scans were done for all mTBI patients. RESULTS: Brain CT scans showed no intracranial traumatic lesions. The median levels for S100B in the mTBI group was 14.8 (4.4-335.9) ng/L, and in orthopedic patients' group was 13.3 (5-353.10) ng/L. Statistically significant differences were observed between both groups in S100B levels (p=0.006). The median Glial Fibrillary Acidic Protein (GFAP) levels in the mTBI patients' group were 600 (400-16300) and in the orthopedic patients' groups was 60 ng/L (300-14900). Statistically significant differences were observed between groups in GFAP (p=0.041). CONCLUSION: Our results showed that S100B and GFAP serum levels were significantly higher in patients with mTBI than in patients with a single limb fracture.

Inhibition of USP14 induces ER stress-mediated autophagy without apoptosis in lung cancer cell line A549.

Non-small cell lung cancer is the most common type of lung cancer, accounting for more than 80% of this tumor. Ubiquitin-specific protease (USP) 14 is one of the 100 deubiquitinating enzymes that is overexpressed in lung cancer and has been validated as a therapeutic target. The aim of this study is to determine whether the accumulation of ubiquitinated proteins results in endoplasmic reticulum (ER) stress-mediated autophagy. To inhibit USP-14, A549 lung cancer cells were treated with USP-14 siRNA and IU1-47 (20 µM). The protein level, mRNA expression, and cell cycle analysis were evaluated using Western blot, real-time PCR, and flow cytometry, respectively. We found that treating A549 cells with USP14 inhibitors significantly reduced the proliferation rate and induced cell cycle arrest at G2/M phase. We also found that USP14 inhibitors did not induce apoptosis but actually induced autophagy through accumulation of ubiquitinated proteins/ER stress/unfolded protein response (UPR) axis. Moreover, we have for the first time demonstrated that the USP14 inhibition induces ER stress-mediated autophagy in A549 cells by activation of c-Jun N-terminal kinase 1 (JNK1). In conclusion, the current investigation represents a new mechanism by which inhibition of USP14 triggers autophagy via ER stress-mediated UPR in A549 cells.

Protection of renal damage by HMG-CoA inhibitors: A comparative study between atorvastatin and rosuvastatin.

OBJECTIVES: 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) (P<0.01), atherogenic index (AI) (P<0.01), MDA (P<0.01), and OX-LDL (P<0.01); no significant differences were noted in their cholesterol (P=0.72), triglyceride (TG) (P=0.79), and very low density lipoprotein cholesterol lowering (VLDL-C) (P=0.79) and high density lipoprotein cholesterol elevating effects (HDL-C) (P=0.72). Ator was more effective to reduce renal histopathologic indices compared to Ros, including accumulation of lipid droplet, glomerular foam cells, mesangial cell proliferation, renal hemorrhage, and tubulointerstitial damages in the kidneys of diet induced hypercholesterolemic rats. CONCLUSION: The findings underline that the lipophilic Ator may performs better than Ros in attenuating renal damages in HCDIHR.

Empagliflozin Attenuates Renal and Urinary Markers of Tubular Epithelial Cell Injury in Streptozotocin-induced Diabetic Rats.

Empagliflozin, a SGLT-2 inhibitor, improves diabetic nephropathy through its pleiotropic anti-inflammatory effects. The present study aims to evaluate empagliflozin effects on renal and urinary levels of tubular epithelial cell injury markers in streptozotocin-induced diabetic rats. Empagliflozin at 10 mg/kg (p.o.) was administered for 4 weeks, beginning 8 weeks after induction of diabetes. Renal function as well as markers of renal tubular epithelial cell injury were assessed in kidney tissue homogenates and urine. Empagliflozin was able to ameliorate diabetes induced elevations in serum cystatin C levels. It also alleviated renal KIM-1/NGAL levels and urinary albumin, α-GST, and RBP excretions. In addition to decreasing urinary levels of cell cycle arrest indices i.e. TIMP-2 and IGFBP7, empagliflozin mitigated acetylated NF-κB levels in renal tissues of diabetic rats. As a whole, these findings reveal empagliflozin capability in improving diabetic nephropathy via ameliorating indices of renal inflammation, injury, and cell cycle arrest on streptozotocin-induced diabetic rats.

Sodium-glucose co-transporters and diabetic nephropathy: Is there a link with toll-like receptors?

The incidence of diabetes mellitus (DM) has increased alarmingly over the last decades. Despite taking measures aimed at controlling hyperglycaemia and blood pressure, the rate of end-stage renal disease (ESRD) is continually growing. Upon increased amounts of advanced glycation end products (AGEs) and their correspondent receptors (RAGEs), AGE-RAGE axis is over-activated in DM, being the first step in the initiation and propagation of inflammatory cascades. Meanwhile, HMGB1, released from damaged cells in the diabetic kidneys, is the most notable ligand for the highly expressed toll-like receptors (TLRs) and RAGEs. TLRs play an indispensable role in the pathogenesis of diabetic nephropathy. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are hypoglycaemic agents acting on the renal proximal tubules to prevent glucose reabsorption and therefore increase urinary glucose excretion. Besides improving glycaemic control, these hypoglycaemic agents possess direct renoprotective properties. Here, therefore, we review the most recent findings regarding interrelationship between SGLT2 inhibitors and HMGB1-TLR4 axis.

Anti-tumor Effect of Quercetin Loaded Chitosan Nanoparticles on Induced Colon Cancer in Wistar Rats.

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.

Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis.

OBJECTIVES: 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.

Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat.

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade

FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats.

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.

AGE-RAGE axis blockade in diabetic nephropathy: Current status and future directions.

Diabetic nephropathy is one of the most frequent micro-vascular complications both in type 1 and type 2 diabetic patients and is the leading cause of end-stage renal disease worldwide. Although disparate mechanisms give rise to the development of diabetic nephropathy, prevailing evidence accentuates that hyperglycemia-associated generation of advanced glycation end products (AGEs) plays a central role in the disease pathophysiology. Engagement of the receptor for AGE (RAGE) with its ligands provokes oxidative stress and chronic inflammation in renal tissues, ending up with losses in kidney function. Moreover, RAGE activation evokes the activation of different intracellular signaling pathways like PI3K/Akt, MAPK/ERK, and NF-κB; and therefore, its blockade seems to be an attractive therapeutic target in these group of patients. By recognizing the contribution of AGE-RAGE axis to the pathogenesis of diabetic nephropathy, agents that block AGEs formation have been at the heart of investigations for several years, yielding encouraging improvements in experimental models of diabetic nephropathy. Even so, recent studies have evaluated the effects of specific RAGE inhibition with FPS-ZM1 and RAGE-aptamers as novel therapeutic strategies. Despite all these promising outcomes in experimental models of diabetic nephropathy, no thorough clinical trial have ever examined the end results of AGE-RAGE axis blockade in patients of diabetic nephropathy. As most of the AGE lowering or RAGE inhibiting compounds have emerged to be non-toxic, devising novel clinical trials appears to be inevitable. Here, the current potential treatment options for diabetic nephropathy by AGE-RAGE inhibitory modalities have been reviewed.

Dunnione protects against experimental cisplatin-induced nephrotoxicity by modulating NQO1 and NAD+ levels.

Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed. Dunnione repressed cisplatin-induced inflammation in the kidneys as indicated by decreased TNF-α/IL-1ß levels, and reduced nuclear phosphorylated NF-κB p65. This agent also obviated cisplatin-invoked oxidative stress as elucidated by decreased MDA/GSH levels and increased SOD/CAT activities. Dunnione, furthermore, improved renal histological deteriorations as well as caspase-3 activities and terminal deoxynucleotidyl transferase (TUNEL) positive cells, the indicators of apoptosis. Moreover, it up-regulated nuclear Nrf2 and cytosolic haeme-oxygenase-1 (HO-1) and NQO1 levels; meanwhile, promoted NAD+/NADH ratios followed by enhancing the activities of Sirt1 and PARP1; and further attenuated nuclear acetylated NF-κB p65. Dunnione additionally declined cisplatin-evoked retrogression in renal function and upraise in urinary markers of glomerular and tubular injury as demonstrated by decreased serum urea and creatinine with simultaneous reductions in urinary excretions of collagen type IV, podocin, cystatin C, and retinol-binding protein (RBP). Altogether, these findings offer dunnione as a potential protective agent against cisplatin-induced nephrotoxicity in rats.

Relationship of Serum Klotho Level With ACE Gene Polymorphism in Stable Kidney Allograft Recipients.

INTRODUCTION: The kidney is the main source of serum Klotho production. Immunosuppressive agents could affect the kidney in this regard. The effect of the ACE gene polymorphism on Klotho production is a less studied area. This study aimed to assess serum Klotho and ACE gene in a group of stable kidney transplant recipients. MATERIALS AND METHODS: In a cross-sectional study, 30 kidney transplant recipients with stable allograft function and 27 healthy young individuals were assessed for their serum Klotho levels. The ACE gene polymorphisms were studied in both groups. RESULTS: Klotho level was higher in kidney transplant recipients than the controls, but the difference was not significant (2.76 ± 2.41 ng/mL versus 2.01 ± 1.41 ng/mL, respectively). In both groups, serum Klotho level was higher in those with the I>I polymorphism, the men, those with higher glomerular filtration rate, and younger individuals, but the differences did not reach a significant level. Higher body mass index was significantly associated with lower serum Klotho level in both groups. CONCLUSIONS: Klotho level after kidney transplantation meets the range in healthy individuals, and it is not affected by the ACE gene polymorphism.

Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women.

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<0.001) and the level of TAC in fertile women was significantly higher than infertile women (p<0.001). Spearman test revealed a significant and direct correlation between melatonin and TAC in fertile and infertile women and a significant but reverse correlation between melatonin and MDA in infertile and fertile women. CONCLUSION: Differences in the level of oxidative stress biomarkers in fertile and infertile individuals have been reported. This study revealed a significant correlation between melatonin and oxidative stress biomarkers, concluding that melatonin level could be involved in infertility.

Effects of zinc supplementation on serum zinc and leptin levels, BMI, and body composition in hemodialysis patients.

PROJECT: The aim of this study was to determine the effects of zinc supplementation on serum zinc and leptin levels as well as on anthropometric status and some biochemical parameters in hemodialysis (HD) patients. PROCEDURE: In this randomized, double-blind, and placebo-controlled trial, sixty HD patients were randomly divided into groups to receive a daily supplement of 100mg elemental Zn (supplemented group) or placebo (control group) for 60 days. Anthropometric measurements were taken using standard calibrated instruments. Serum zinc and leptin levels were determined by atomic absorption and ELISA method respectively before and after intervention. RESULTS: Zinc supplementation resulted in significant increase in the mean serum zinc level in the experimental group while changes observed in the placebo group were not significant. The mean serum leptin in women part of the experimental group was decreased significantly after supplementation. After adjusting for age, BMI, body fat (%), serum zinc and dietary Zn intake, a negative and significant association was observed between serum zinc and leptin levels in all subjects (ß=-0.33, P=0.03) as a result of Zn supplementation. CONCLUSIONS: More studies are needed to clarify the mechanisms by which serum leptin level is influenced as a result of zinc supplementation in HD patients.

Serum Levels of Melatonin and Oxidative Stress Markers and Correlation between Them in Infertile Men.

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.

Pharmacological preconditioning with L-carnitine: relevance to myocardial hemodynamic function and glycogen and lactate content.

Carnitine is a vital biologic substance facilitating fatty acids transport into mitochondria for ATP production. This study was to investigate the effects of pre-ischemic pharmacological preconditioning (PC) with L-carnitine (L-Car) on myocardial infarct size and cardiac functions in ischemic and reperfused isolated rat heart and meanwhile on left ventricular glycogen and lactate content. Isolated rat hearts were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion. The hearts (n= 8-12) were perfused with L-Car (0.5-5 mM) only for 15 min before to 10 min after induction of ischemia. Preconditioning of the hearts with L-Car provided concentration-dependent cardioprotection as evidenced by improved postischemic ventricular functional recovery (developed pressure, left ventricular end diastolic pressure and coronary flow rate) and reduced myocardial infarct size (p<0.001). L-Car (2.5 mM) decreased both glycogen (p<0.001) and lactate (p>0.05) content in left ventricle during ischemia compared with the control. The results of this study demonstrate that L-Car pharmacologically precondition the hearts against ischemic and reperfusion injury in part by recovery of postischemic ventricular hemodynamic functions, depletion of glycogen and therefore reduction of lactate accumulation.