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 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.

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.

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.

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.

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.

Dietary L-arginine and cutaneous wound healing.

Skin wound healing has been the subject of extensive studies and various drugs have been used in an attempt to improve wound healing. There are conflicting data regarding the effects of L-arginine, the substrate of nitric oxide, on wound healing. We examined the 1-week rate of cutaneous wound healing and collagen deposition in three groups of rats who received a (1) L-arginine (2% in drinking water)-supplemented diet from three days before until the seventh day following injury (Group 1), (2) L-arginine-supplemented diet for three days before injury (Group 2), and (3) a standard diet without L-arginine supplementation (Group 3). The wound length and width were measured each day and then the open wound area and cumulative percentage of open wound area reduction were calculated. Wound biopsy samples were examined with Trichrome-Masson stain in a subgroup of animals. Results showed that Group 1 rats had a significantly lower cumulative percentage of open wound area reduction on day 7 compared to other two groups (Mann-Whitney U test, P < 0.05). Relatively higher degrees of wound collagen deposit (day 7) were noted in groups 2 and 3. It may be concluded that L-arginine (2% in water) administered three days before until the seventh day following skin wound induction may diminish the rate of skin wound healing and collagen deposition.