STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells.

BACKGROUND: Induction of immunogenic cell death (ICD) is considered a promising strategy for cancer immunotherapy. Stattic is an inhibitor of STAT3, which is found constitutively active in many cancers and plays a major role in cancer progression. OBJECTIVES: In the present study, we proposed to evaluate whether stattic can enhance the effects of chemotherapy in the induction of ICD in cancer cells harboring hyperactive STAT3. METHODS: The growth inhibitory effects of stattic and chemo agents including doxorubicin (DOX) and oxaliplatin (OXP) were evaluated using MTT assay in B16F10 and CT26 cell lines. Flow cytometry was applied to study cell apoptosis and calreticulin (CRT) surface exposure. The levels of high mobility group box 1 (HGMB1), heat shock protein70 (HSP70) and interleukin-12 (IL-12) were measured using ELISA. RESULTS: Treatment of B16F10 and CT26 cells with stattic in combination with DOX resulted in synergistic antitumor effects with combination index being 0.82 and 0.87, respectively. Interestingly, we found a higher level of ICD markers including CRT expression as well as HMGB1 and HSP70 secretion in the cells received combination therapy of stattic and DOX as compared with monotherapies. Moreover, exposure of dendritic cells (DCs) to conditioned media (CM) from cancer cells treated with stattic and/or DOX resulted in secretion of IL-12, which is an indicator of DCs maturation and induction of Th1 response. OXP and stattic monotherapy induced ICD in CT26 cells and stimulated IL-12 secretion by DCs; however, we did not observe a significant increase in the level of ICD in CT26 cells and IL-12 secretion by DCs when CT26 cells were treated with stattic and OXP combination as compared with monotherapy groups. CONCLUSION: These findings indicate that STAT3 inhibitory stattic can increase ICD induced by DOX. Graphical abstract.

Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: A controlled randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effects of cholecalciferol supplementation on serum levels of angiogenic parameters in patients with breast cancer (BC) who were treated with tamoxifen. METHODS: This was a pilot-based, randomized, triple-blind, placebo-controlled clinical trial with 52 patients with BC randomly assigned to either an intervention group receiving weekly 50 000 IU cholecalciferol or a placebo group for 8 wk. At baseline and at end of study, serum levels of angiogenic growth factors such as vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, hypoxia-inducible factor (Hif)-1, and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Every 4 wk, a completed 3-d, 24-h dietary record and daily sunlight exposure checklist were collected and anthropometric variables were measured. RESULTS: The ultimate number of participants in each arm was 22 for analyses. For premenopausal women, cholecalciferol supplementation resulted in a significant decrease in serum levels of Ang-2 and VEGF-A after 8 wk of treatment (P < 0.05). In the absence of vascular invasion, supplementation led to a significant decrease in Ang-2 levels compared with the placebo group (P < 0.05). Supplementation caused significant increases in Hif-1 in patients diagnosed with the infiltration of tumors into vascular or lymphatic vessels (P < 0.05). CONCLUSION: Cholecalciferol supplementation achieved sufficient efficacy among patients with BC taking tamoxifen and could be effective in the reduction of angiogenic biomarkers particularly dependent on the infiltration status of the tumor to vessels. Further studies with larger subgroups should be investigated.

Effect of Sevelamer on Serum Levels of Klotho and Soluble Tumor Necrosis Factor-like Weak Inducer of Apoptosis in Rats With Adenine-induced Chronic Kidney Disease.

INTRODUCTION: Nontraditional risk factors for cardiovascular disease (CVD), including mineral disorder, high fibroblast growth factor 23 (FGF23), low klotho, and low soluble TWEAK could predict the incipient risk of CVD in chronic kidney disease (CKD). The present study evaluates the effect of sevelamer on soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and klotho levels in adenine-induced CKD rats. METHODS AND MATERIALS: Normal control rats without sevelamer were compared with 3 groups of adenine-induced CKD rats, including CKD rats without sevelamer, CKD rats treated with 3% sevelamer, and rats receiving adenine and 3% sevelamer concurrently. After 4 weeks of sevelamer treatment, serum levels of klotho and soluble TWEAK were measured, along with biochemical parameters related to kidney function. RESULTS: Sevelamer significantly reduced serum levels of phosphate and increased serum levels of klotho and soluble TWEAK. Decreased levels of phosphate were negatively correlated with elevated levels of klotho and soluble TWEAK (r = -0.70, P = .003; r = -0.58, P = .02; respectively) in serum. CONCLUSIONS: Sevelamer successfully reduced serum levels of phosphate, and meanwhile, it led to an elevation in serum levels of klotho and soluble TWEAK in rat models of CKD.

Effect of Ferula persica plant methanol extract on the level of Cox-2 in induced squamous cell carcinoma (SCC) in rat tongue.

Background: More than 90% of oral cancers are cases of squamous cell carcinoma. Standard treatment of cancer includes a combination of surgery, chemotherapy and radiotherapy. Each of these treatments, however, brings about certain problems and side effects. Today herbal medicine, has become a more preferable option in dealing with health problems or preventing them because this type of medicine has better compatibility with the body and does not cause undesirable side effects. In this study , the effect of Ferula persica plant methanol extraction on Cox-2 levels in SCC induced rat tongue is conducted in vivo. Methods: In this lab research, 75 rats from SD race in the age - range of 2/5 - 3 months were selected and put in five groups. In order to induce tongue carcinoma, 4- Nitroquinoline 1 (4 NQO) powder was used 3 times a week for each rat. Furthermore, Ferula persica extract was given to each of the groups in order to examine Cox-2 changes in the blood. Results: Comparison of Cox-2 average in various groups resulted in the observation that there was significant difference between the Cox-2 levels in the groups which had only received carcinogen and the other groups. In this group, Cox-2 level was less and in the group that had received Ferula extract (500 mg) along with carcinogen , Cox-2 level was found to be more than other groups. Conclusion: Ferula persica extract does not have reducing effect on serum Cox-2.

Effects of separate and concurrent supplementation of Nano-sized clinoptilolite and Nigella sativa on oxidative stress, anti-oxidative parameters and body weight in rats with type 2 diabetes.

OBJECTIVES: The objective of this study was to investigate the effects of separate and concurrent supplementation of natural nano-sized clinoptilolite (NCLN) and Nigella sativa (NS) on oxidative stress (OS), anti-oxidative parameters and body weight (BW) in high-fat-diet (HFD)/streptozotocin (STZ)-induced diabetic rats. METHODS: In this experimental study, 42 male Wistar rats were divided into diabetic (n=36) and non-diabetic (n=6) groups. The diabetic group (DG) was fed with a HFD for one month, then injected with intra-peritoneal single dose STZ (35 mg/kg BW). The DG was divided into 4 subgroups: [1] control (DC), [2] NS 1%/food, [3] NCLN 2%/food, [4] NS 1%/food + NCLN 2%/food. At the end of the 7th week, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) levels and total antioxidant capacity (TAC) were measured. RESULTS: The MDA level was decreased in the NCLN (p = 0.011) and NCLN+NS (p = 0.007) groups compared to the DC group. The GPX level increased in the NS and NCLN groups compared to the DC group (p = 0.014 and p = 0.034). In addition, the level of TAC demonstrated increase in the untreated DG and NS groups, as compared to the normal control (NC) group (pDC = 0.031 and pNS = 0.024). Moreover, in the NS+NCLN group, the level of SOD decreased in comparison to the NS and NCLN groups (p < 0.01). At the end of the 7th week, BW decreased in the diabetic subgroups in comparison to the NC group. Treatment with NS and/or NS+NCLN insignificantly prevented severe weight loss in the fifth week of the treatment. CONCLUSIONS: According to results, separate supplementation of NS and NCLN was more beneficent on anti-oxidative parameters than concurrent supplementation of NS and NCLN.

The Effect of Furosemide on the Level of Neutrophil Gelatinase-associated Lipocalin in Critically Hospitalized Patients with Acute Kidney Injury.

BACKGROUND AND AIMS: Oliguric acute kidney injury (AKI), commonly attributed to a more severe degree of renal injury, is associated with poorer prognosis than nonoliguric form. The aim of this study was to determine the effect of furosemide therapy on kidney function and on the level of neutrophil gelatinase-associated lipocalin (NGAL) in critically hospitalized patients in the Intensive Care Unit (ICU). MATERIALS AND METHODS: In this randomized controlled trial, 106 ICU patients with AKI were assigned into furosemide and control groups. In furosemide group, 40-80 mg of intravenous furosemide was administrated, followed by 1-5 mg/h furosemide infusion. In control group, patients received standard treatment. Serum and urinary NGAL were measured on the 1st, 3rd, and 7th days of the study. RESULTS: The results of this study indicated that during the study, serum blood urea nitrogen levels of patients increased in both groups; this, however, was significant only in the control group (P = 0.009). Both plasma and urine NGAL decreased significantly (P < 0.05) in both groups. The findings of 28-day mortality follow-up revealed that 20% and 28% of patients died in the furosemide and the control groups, respectively. CONCLUSIONS: NGAL was not found to reflect any positive or negative effects of Furosemide in patients with AKI.

Effects of Fresh Yellow Onion Consumption on CEA, CA125 and Hepatic Enzymes in Breast Cancer Patients: A Double- Blind Randomized Controlled Clinical Trial.

Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy.

Protective effect of pioglitazone on morphine-induced neuroinflammation in the rat lumbar spinal cord.

BACKGROUND: Morphine-induced tolerance is associated with the spinal neuroinflammation. The aim of this study was to explore the effects of oral administration of the pioglitazone, the peroxisome proliferator activated receptor gamma (PPAR-γ) agonist, on the morphine-induced neuroinflammation in the lumbar region of the male Wistar rat spinal cord. RESULTS: Co-administration of the pioglitazone with morphine not only attenuated morphine-induced tolerance, but also prevented the up-regulation of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta, and interleukin 6) and nuclear factor-kappa B activity. Administration of the GW-9662 antagonized the above mentioned effects of the pioglitazone. CONCLUSIONS: It is concluded that oral administration of the pioglitazone attenuates morphine-induced tolerance and the neuroinflammation in the lumbar region of the rat spinal cord. This action of the pioglitazone may be, at least in part, due to an interaction with the spinal pro-inflammatory cytokine expression and the nuclear factor-kappa B activity.

Post-weaning environmental enrichment improves BDNF response of adult male rats.

The environment could have long lasting effects on the individual phenotype through developmental plasticity. Early environmental enrichment exerts profound biological effects, most of which are quite beneficial ones. To explore the enduring effects of rearing condition quality on BDNF(1) responses, we reared male Wistar rats from weaning to young-adulthood in three different environmental conditions: 1. Enriched 2. Standard, and 3. Isolated. Then, at the age of 16 weeks, 10 rats from each group were randomly chosen and allocated to six common mix cages. They were kept together for 14 weeks. At the end of the experiment, each rat received ten inescapable foot-shocks. Twelve hours later, the BDNF contents of the amygdala and CA1 sub-region of the dorsal hippocampus were measured. The serum BDNF levels, hematocrit values as well as brain and testis weights were also measured. Results showed that the environmental enrichment led to stronger dorsal hippocampal BDNF response and higher serum BDNF levels, while rats from standard laboratory condition showed higher amygdala BDNF response. Also, enriched animals showed higher brain weight compared to isolation reared rats as well as higher testis weight and hematocrit value compared to animals reared in standard laboratory condition. Rats showed less body weights in isolated condition. In conclusion, the BDNF profile of enriched animals might represent the neurobiological correlate of resilience phenotype under a stressful situation.

Pioglitazone prevents morphine antinociceptive tolerance via ameliorating neuroinflammation in rat cerebral cortex.

BACKGROUND: Opioid induced neuroinflammation is shown to be implicated in opioid analgesic tolerance development. In the present study the effect of pioglitazone on morphine-induced tolerance and neuroinflammation in the cerebral cortex of the rat was investigated. MATERIALS AND METHODS: Various groups of rats received morphine (10mg/kg; ip) and vehicle (po), or morphine (10mg/kg) and pioglitazone (20 or 40 mg/kg; po) once a day for 17 days. In order to determine the possible involvement of PPAR-γ in the pioglitazone effect, one group of rats received PPAR-γ antagonist, GW-9662 (2mg/kg; sc), and pioglitazone (40 mg/kg) and morphine once daily for 17 days. Nociception was assessed using a tail flick apparatus and the percentage of the maximal possible effect was calculated as well. On 18th day, 2h after the last morphine injection, the cerebral cortex of the animals were harvested and the tissue levels of tumour necrosis factor alpha, interleukin-1beta, interleukin-6, interleukin-10 and nuclear factor-kappa B activity were determined. RESULTS: Co-administration of pioglitazone (40 mg/kg) with morphine not only attenuated morphine-induced tolerance, but also prevented the up-regulation of pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-1beta, interleukin-6) and nuclear factor-kappa B activity in the rat cerebral cortex. Moreover, GW-9662 (2mg/kg) administration 30 min before pioglitazone, antagonized the above mentioned pioglitazone-induced effects. CONCLUSION: It is concluded that oral administration of pioglitazone attenuates morphine-induced tolerance. This effect of pioglitazone may be, at least in part, due to its anti-inflammatory property which suppressed the cortical pro-inflammatory cytokine and inhibited of nuclear factor-kappa B activity.

Synthesis and in vitro study of cisplatin-loaded Fe3O4 nanoparticles modified with PLGA-PEG6000 copolymers in treatment of lung cancer.

In the field of cancer therapy, magnetic nanoparticles modified with biocompatible copolymers are promising vehicles for the delivery of hydrophobic drugs such as Cisplatin. The major aim of this effort was to evaluate whether Cisplatin-Encapsulated magnetic nanoparticles improved the anti-tumour effect of free Cisplatin in lung cancer cells. The PLGA-PEG triblock copolymer was synthesised by ring-opening polymerisation of d,l-lactide and glycolide with polyethylene glycol (PEG6000) as an initiator. The bulk properties of these copolymers were characterised using Fourier transform infrared spectroscopy. Cisplatin-loaded nanoparticles (NPs) were prepared by double emulsion solvent evaporation technique and were characterised for size, drug entrapment efficiency (%), drug content (% w/w), and surface morphology. In vitro release profile of cisplatin-loaded NP formulations was determined. Cytotoxic assays were evaluated in lung carcinoma (A549)-treated cells by the MTT assay technique. In addition, the particles were characterised by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The anti-proliferative effect of Cisplatin appeared much earlier when the drug was encapsulated in magnetic nanoparticles than when it was free. Cisplatin-Encapsulated magnetic nanoparticles significantly enhanced the decrease in IC50 rate. The in vitro cytotoxicity test showed that the Fe3O4-PLGA-PEG6000 magnetic nanoparticles had no cytotoxicity and were biocompatible. The chemotherapeutic effect of free Cisplatin on lung cancer cells is improved by its encapsulation in modified magnetic nanoparticles. This approach has the prospective to overcome some major limitations of conventional chemotherapy and may be a promising strategy for future applications in lung cancer therapy.

Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF-α in patient with ESRD undergoing hemodialysis.

BACKGROUND: Chronic renal failure is a progressive and irreversible loss of kidney function, and the hemodialysis (HD) is one of the most common modalities in this regard. Oxidative stresses [like interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α)] and inflammation are the main risk factors associated with cardiovascular diseases and other complications in many organs in hemodialysis patients; meanwhile, antioxidants like alpha lipoic acid (ALA) may reduce the oxidative stress markers and the levels of inflammatory cytokines, so can improve of the patient's quality of life. METHODS: In this randomized clinical trial study, 60 HD patients were randomly categorized in two case and control groups. Case group received a daily capsule of 600 mg of ALA supplementation for 8 weeks, and the control group received placebo capsules daily. The serum level of IL-8 and TNF-α was measured in both groups before and after the intervention. RESULTS: There were no significant differences in age, gender, duration of dialysis, and causative factor for dialysis between both groups (P > 0.05). The mean of IL-8 and TNF-α after the intervention in case group was 26.20 ± 15.34 and 21.25 ± 9.61, respectively; the difference between both groups was not statistically significant (P > 0.05). CONCLUSION: Based on the better feeling and other beneficial effects of ALA were found in our study; we can conclude that it is a beneficial and recommended supplement, especially, for diabetic and dialysis patients.

The effect of erythropoietin on ischemia/reperfusion injury after testicular torsion/detorsion: a randomized experimental study.

This study was conducted to investigate the protective effect of erythropoietin (EPO) on ischemia/reperfusion related changes after testicular torsion/detorsion. In a randomized experimental trial 30 male rats were randomly allocated into six equal groups of five rats each. Group I (orchiectomy for histopathologic examination), group II (sham operation), group III (torsion for 2 hours, and ischemia/detorsion for 24 hours, and orchiectomy); group IV (torsion for 2 hours, ischemia/detorsion for 24 hours with erythropoietin injection then orchiectomy), group V (torsion for 2 hours and detorsion and EPO injection and orchiectomy 1 week later, group VI (torsion for 2 hours/detorsion and orchiectomy 1 week later). Two groups (groups 4 and 5) received different protocols of erythropoietin administration after testicular torsion/distortion. other groups were not receiving erythropoietin. Johnsen's spermatogenesis scoring method and Cosentino's histologic staging method were used to assess main outcome measures of the study. After the experimentation, Johnsen's score in EPO Groups was statistically different from the score in some groups not receiving erythropoietin. Cosentino's score in EPO groups was statistically different from the score in all groups not receiving erythropoietin. Neovascularization, vascular necrosis, vascular congestion, edema, hemorrhage, and acute inflammation were observed in some groups. This study shows short-term protective efficacy of erythropoietin on rat testicular injury after ischemia/reperfusion.

A comparative study of the burn wound healing properties of saline-soaked dressing and silver sulfadiazine in rats.

The purpose of this study was to further investigate that phenomenon and to explore the effect silver sulfadiazine on wound healing. Full-thickness burn wounds were created on the dorsum of Wistar albino rats under anesthesia. The wounds were treated with silver sulfadiazine and saline-soaked dressing for fourteen days, and then observed until healed. Wound surface area was measured each three days. Time to 50% and 90% healing was compared. No clinical infections occurred. Wound half-life and healing times were shortest in the saline-soaked group (P < 0.0001) in full-thickness burns. Wound contraction was delayed by silver sulfadiazine. These data suggest that silver sulfadiazine retard burn wound healing. Infection control without delay of burn wound healing is most appealing and clinical trials are planned.

Protective effect of grape seed extract on gentamicin-induced acute kidney injury.

INTRODUCTION. This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHODS. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. RESULTS. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P < .001). CONCLUSIONS. This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury.

Prevention of selenite-induced cataractogenesis in Wistar albino rats by aqueous extract of garlic.

PURPOSE: The main aim of this study was to evaluate the inhibitory impacts of the aqueous extract of garlic (Ga) on the formation of cataract induced by sodium selenite (Se). METHODS: Thirty-two Wistar albino rat pups (4 equal groups: G1, G2, G3, and G4) were treated as follows: G1, subcutaneous (s.c.) and intraperitoneal (i.p.) injection of normal saline (0.3 mL) on postpartum (day 10); G2, i.p. injection of aqueous extract of garlic (1 mL/kg body weight) and s.c. injection of normal saline (0.3 mL) on postpartum (day 10); G3, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of normal saline (0.3 mL) on postpartum (day 10); and G4, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of aqueous extract of garlic (1 mL/kg body weight) on postpartum (day 10). Daily i.p. injections of aqueous extract of garlic (in G2 and G4) and normal saline (in G1 and G3) were continued for 14 days. The development of cataract was assessed over a period of 2 weeks after injection of sodium selenite. For further examination, the rats' lenses were removed and analyzed for glutathione (GSH), malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX) activities. RESULTS: In G3 (Se-treated group), all rats developed grade 3 cataract in both eyes. However, in G1 (untreated control group), G2 (Ga-treated group), and G4 (Ga-Se-treated group), the lenses in both eyes of all rats remained clear (P < 0.0001). This clinical finding was associated with higher GSH level and GPX, SOD activities and lower level of MDA in the Se- and Ga-treated group (G4) compared with SS-treated group (G3) rat lenses (P < 0.003). CONCLUSIONS: Intraperitoneal injection of the Ga in rat model appeared to effectively prevent Se-induced cataract, thus such herbal remedy may be considered for treatment of cataract.

Preventive effect of onion juice on selenite-induced experimental cataract.

PURPOSE: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. MATERIALS AND METHODS: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). RESULTS: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). CONCLUSION: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

The effects of aerobic exercise training on the age-related lipid peroxidation, Schwann cell apoptosis and ultrastructural changes in the sciatic nerve of rats.

The potential role of exercise in preventing the age-related spontaneous peripheral neuropathy has not been studied. We examined the effects of long-term aerobic exercise training on lipid peroxidation, Schwann cell (SC) apoptosis and ultrastructural changes in the sciatic nerve of rats during aging. Three groups of 12-week old Wistar rats ran on a treadmill for 6, 9 and 12 months (exercise trained (ET) group, n=10 each) according to an exercise training program targeted at a speed of 22 m/min (at 7 degrees incline), 60 min/day, 6 days/week. Three corresponding groups of untrained rats were used as the controls (sedentary (SED) group). At the end of each period, sciatic nerve biopsies were performed, and processed for biochemical, immunohistochemical and ultrastructural analyses. The results showed that aging was associated with an increased level of nerve malondialdehyde (MDA, marker of lipid peroxidation) and a higher number of SC apoptosis in SED group. The SED group showed irregular nerve fibers with thin myelin sheaths and areas of myelin-axon detachment. However, the ET group had significantly diminished nerve lipid peroxidation and SC apoptosis. In the ET group, nerve fibers had a thick myelin sheath with frequent folding. These findings suggest that aerobic exercise training protects peripheral nerves by attenuating oxidative reactions, and preserving SCs and myelin sheath from pathologic changes, which occur during normal aging.

Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms.

BACKGROUND: In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms. METHODS: After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively. RESULTS: 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P < 0.001; r = 0.35, P = 0.006). CONCLUSION: The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.

Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury.

INTRODUCTION: Melatonin, the secretory product of the pineal gland, has potent antioxidant properties. The aim of this study was to compare the effects of low-dose (10 mg/kg) vs high-dose (50 mg/kg) melatonin on early lipid peroxidation levels and ultrastructural changes in experimental blunt sciatic nerve injury (SNI). We believe this to be the first study to assess the dose-dependent neuroprotective effects of melatonin after a blunt peripheral nerve injury. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups of 10 animals each. The SNI only rats underwent a nerve injury procedure. The SNI plus vehicle group received SNI and intraperitoneal injection of vehicle (diluted ethanol) as a placebo. The SNI plus low-dose or high-dose melatonin groups received intraperitoneal melatonin at doses of 10 mg/kg or 50 mg/kg, respectively. Controls had no operation, melatonin or vehicle injection. SNI was induced by clamping the sciatic nerve at the upper border of the quadratus femoris for 2 min. RESULTS: Sciatic nerve samples were harvested 6 h after nerve injury and processed for biochemical and ultrastructural analysis. Trauma increased the lipid peroxidation of the sciatic nerve by 3.6-fold (153.85 +/- 18.73 in SNI only vs 41.73 +/- 2.23 in control rats, P < 0.01). Low (P = 0.02) and high (P < 0.01) doses of melatonin attenuated the nerve lipid peroxidation by 25% and 57.25%, respectively (65.76 +/- 2.47 in high-dose vs 115.08 +/- 7.03 in low-dose melatonin groups). DISCUSSION: Although low-dose melatonin reduced trauma-induced myelin breakdown and axonal changes in the sciatic nerve, high-dose melatonin almost entirely neutralized any ultrastructural changes. CONCLUSION: Our results suggest that melatonin, especially at a dose of 50 mg/kg, has a potent neuroprotective effect and can preserve peripheral neural fibers from lipid peroxidative damage after blunt trauma. With further investigations, we hope that these data may prove useful to clinicians who treat patients with nerve injuries.