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1.  Protection of Renal Tubular Cells by Antioxidants: Current Knowledge and New Trends 
Cell Journal (Yakhteh)  2015;16(4):568-571.
Acute renal damage mainly develops following toxic or ischemic insults and is defined as acute. These damages have largely been attributed to oxidative stress. Recently much attention has been directed toward decreased renal tubular cell regeneration during tubular cell injury. Antioxidants have recently been the focus of researchers and scientists for prevention and treatment of various oxidative stress-related conditions, including renal toxicities. Although free radicals are known to contribute in kidney injury and abundant researches, particularly laboratory trials, have shown the beneficial effects of antioxidants against these complications, long term clinical trials do not uniformly confirm this matter, especially for single antioxidant consumption such as vitamin C. The aim of this paper is to discuss the possible explanation of this matter.
PMCID: PMC4297497
Acute Renal Injury; Kidney Injury; Antioxidants; Oxidative Stress
3.  Comment on: effect of pomegranate flower extract oncis platin-induced nephrotoxicity in rats 
Journal of Nephropathology  2014;3(4):121-123.
PMCID: PMC4219612  PMID: 25374879
Nephrotoxicity; Cisplatin; Pomegranate
4.  World Cancer Day 2014: "Increasing The Awareness" 
Cell Journal (Yakhteh)  2014;16(3):383-384.
PMCID: PMC4204181  PMID: 24611153
World Health Organization; Cancer; Patients
5.  Effect of Dietary Ethanolic Extract of Lavandula officinalis on Serum Lipids Profile in Rats 
Antioxidants are effective in prevention and treatment of cardiovascular diseases. Lavandula officinalis possesses antioxidant activity, therefore, in this study; the effects of Lavandula officinalis extract were investigated on serum lipids levels of rats. Experimental mature male Wistar rats were treated with 100, 200 or 400 mg/Kg/day of lavender ethanolic extract or distilled water for 25 days via gastric gavage (n=8 each group). At the end of 25th day, the serum cholesterol, triglyceride, HDL, LDL and VLDL levels, as well as atherogenic indices were determined in rats’ serum. The ethanolic extract of lavender decreased serum cholesterol, triglyceride, LDL and VLDL levels in 100 mg/Kg group (p=0.03, p=0.001, p=0.001, p=0.001, respectively). Serum HDL level increased in 100 mg/Kg/day group (p=0.01). Lavender extract decreased LDL/HDL level at doses of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). The TG/HDL levels decreased in experimental groups with doses of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). Lavandula officinalis extract exerts hypolipidemic effect in rats and might be beneficial in hyperlipidemic patients.
PMCID: PMC4232795  PMID: 25587318
Lavandula officinalis; Serum lipids; Atherogenic index; Cardiovascular
6.  Protective Effects of Metformin on Renal Tubular Cells 
PMCID: PMC4270682  PMID: 25593707
Metformin; Kidney; Toxicity
7.  Anethum graveolens and hyperlipidemia: A randomized clinical trial 
It has been established that hyperlipidemia increases the incidence and mortality associated with coronary heart disease. In this study, the effects of Dill (Anethum graveolens) were evaluated on lipid profile of hypercholesterolemic patients.
Materials and Methods:
In this clinical study, 91 hyperlipidemic patients were randomly designated into two groups. One group received gemfibrozil (900 mg daily) and the other group received Dill tablet (six tablets daily) for 2 months. The blood lipids including total cholesterol, triglyceride and high density lipoprotein (HDL)-cholesterol from each group were assessed at the beginning and end of the trial.
Use of gemfibrozil brought about increased HDL-cholesterol by 3.91% (P < 0.05) and reduced triglyceride and total cholesterol by 32.7% (P < 0.05) and 9.41% (P < 0.05), respectively. Applying Dill tablet for 2 months resulted in reduction of total cholesterol up to 18% (P < 0.05) and triglyceride by 7.38% (P < 0.05). However, circulating HDL-cholesterol was not affected by this treatment. In this study, gemfibrozil decreased triglyceride and increased HDL-cholesterol more than anethum (P < 0.05). Anethum decreased total cholesterol more than gemfibrozil (P < 0.05). Patients treated with anethum did not report any side effects.
The results of this trial indicate that Dill might be beneficial for hypercholesterolemic and hypertriglycemic patients.
PMCID: PMC4235097  PMID: 25422662
Anethum graveolens; gemfibrozil; high density lipoprotein-cholesterol; total cholesterol; triglyceride
8.  Atherosclerosis: Process, Indicators, Risk Factors and New Hopes 
Atherosclerosis is the major cause of morbidities and mortalities worldwide. In this study we aimed to review the mechanism of atherosclerosis and its risk factors, focusing on new findings in atherosclerosis markers and its risk factors. Furthermore, the role of antioxidants and medicinal herbs in atherosclerosis and endothelial damage has been discussed and a list of important medicinal plants effective in the treatment and prevention of hyperlipidemia and atherosclerosis is presented.
The recently published papers about atherosclerosis pathogenesis and herbal medicines effective in the treatment and prevention of hyperlipidemia and atherosclerosis were searched.
Inflammation has a crucial role in pathogenesis of atherosclerosis. The disease is accompanied by excessive fibrosis of the intima, fatty plaques formation, proliferation of smooth muscle cells, and migration of a group of cells such as monocytes, T cells, and platelets which are formed in response to inflammation. The oxidation of low density lipoprotein (LDL) to Ox-LDL indicates the first step of atherosclerosis in cardiovascular diseases. Malondialdehyde factor shows the level of lipoperoxidation and is a sign of increased oxidative pressure and cardiovascular diseases. In special pathological conditions such as severe hypercholesterolemia, peroxynitrite concentration increases and atherosclerosis and vascular damage are intensified. Medicinal plants have shown to be capable of interacting these or other pathogenesis factors to prevent atherosclerosis.
The pathogenesis factors involved in atherosclerosis have recently been cleared and the discovery of these factors has brought about new hopes for better prevention and treatment of atherosclerosis.
PMCID: PMC4258672  PMID: 25489440
Atherosclerosis; inflammation; lipids
9.  Metformin: Current knowledge 
Diabetes mellitus is a group of metabolic disorders in which the blood glucose is higher than normal levels, due to insufficiency of insulin release or improper response of cells to insulin, resulting in high blood pressure. The resultant hyperglycemia produces sever complications. Metformin drug has been shown to prevent diabetes in people who are at high risk and decrease most of the diabetic complications. Recent reports on metformin, not only indicate some implications such as renoprotective properties have been suggested for metformin, but some reports indicate its adverse effects as well that are negligible when its benefits are brought into account. We aimed here to review the new implications of metformin and discuss about the concerns in the use of metformin, referring to the recently published papers.
PMCID: PMC4214027  PMID: 25364368
Diabetes; diabetes mellitus; diabetic nephropathy; glucose; metformin; new applications; polycystic ovary syndrome; renoprotection
10.  Cheese consumption in relation to cardiovascular risk factors among Iranian adults- IHHP Study 
Nutrition Research and Practice  2014;8(3):336-341.
It is expected that dairy products such as cheeses, which are the main source of cholesterol and saturated fat, may lead to the development or increase the risk of cardiovascular and metabolic diseases; however, the results of different studies are inconsistent. This study was conducted to assess the association between cheese consumption and cardiovascular risk factors in an Iranian adult population.
Information from the Isfahan Healthy Heart Program (IHHP) was used for this cross-sectional study with a total of 1,752 participants (782 men and 970 women). Weight, height, waist and hip circumference measurement, as well as fasting blood samples were gathered and biochemical assessments were done. To evaluate the dietary intakes of participants a validated food frequency questionnaire, consists of 49 items, was completed by expert technicians. Consumption of cheese was classified as less than 7 times per week and 7-14 times per week.
Higher consumption of cheese was associated with higher C-Reactive Protein (CRP), apolipoprotein A and high density lipoprotein cholesterol (HDL-C) level but not with fasting blood sugar (FBS), total cholesterol, low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apolipoprotein B. Higher consumption of cheese was positively associated with consumption of liquid and solid oil, grain, pulses, fruit, vegetable, meat and dairy, and negatively associated with Global Dietary Index. After control for other potential confounders the association between cheese intake and metabolic syndrome (OR: 0.81; 96%CI: 0.71-0.94), low HDL-C level (OR: 0.87; 96%CI: 0.79-0.96) and dyslipidemia (OR: 0.88; 96%CI: 0.79-0.98) became negatively significant.
This study found an inverse association between the frequency of cheese intake and cardiovascular risk factors; however, further prospective studies are required to confirm the present results and to illustrate its mechanisms.
PMCID: PMC4058569  PMID: 24944780
Cheese consumption; cardiovascular risk factors; food frequency questionnaire
11.  In Vitro Impact of Hydro-alcoholic Extract of Rosa damascena Mill. on Rat Ileum Contractions and the Mechanisms Involved 
The petal's hydro-alcoholic extract of Rosa damascena Mill. on ileum contractions of Wistar rats and its possible mechanism were investigated.
Forty-eight male Wistar rats were divided into six groups. Ileum was placed adjacent to propranolol (1 μM), naloxone (1 μM) and L-NAME (100 μM) and also under the influence of different doses (2-8 mM) of calcium chloride.
Cumulative extract of R. damascena Mill. (100, 500, and 1000 mg/L) decreased ileum contractions induced by KCl (60 mM) in a dose-dependent manner (P < 0.0001). Propranolol and naloxone significantly decreased the inhibitory effect of the extract on contractions induced by KCl (P < 0.001), but L-NAME was ineffective. Furthermore, calcium led to the contraction of depolarized tissue through KCI and this contractile effect decreased significantly induced by the cumulative concentrations of the extract (P < 0.001).
The results indicate that R. damascena Mill. dose-dependently (100, 500, and 1000 mg/L) decreases ileum movements of the rat probably through stimulating the β-adrenergic and opioid receptors and voltage-dependent calcium channels, and it may be used to treat digestive disorders.
PMCID: PMC4085930  PMID: 25013697
Ileum; L-NAME; rat; Rosa damascena Mill
12.  In Vitro Evaluation of Antioxidant Properties of Ten Iranian Medicinal Plants 
PMCID: PMC4102973  PMID: 25068040
Antioxidant; Evaluation; Plants, Medicinal
14.  Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine 
To evaluate the effects of berberine (BBR) on the liver phosphatidate phosphohydrolase (PAP) and plasma lipids in rats fed on high lipogenic and normal diet.
Forty rats were randomly divided into 5 groups. Group I (control) received standard diet. Group II received standard diet plus 90 mg/kg BBR and Groups IV received lipogenic diet (containing sunflower oil, cholesterol and ethanol) without treatment. Groups III and V received lipogenic diet plus 90 mg/kg BBR and 30 mg/kg gemfibrozil, respectively. On Day 60 of the experiment, blood samples were collected and PAP, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, very low density lipoprotein, malondialdehyde, plasma antioxidant, and liver histopathology assessments were conducted.
PAP, plasma triglyceride, total cholesterol, very low density lipoprotein, and malondialdehyde levels decreased significantly (P<0.05) in Group III compared to Group IV (24.94%, 36.11%, 21.18%, 36.86% and 19.59%, respectively). The liver triglyceride and cholesterol in Groups III and V had a remarkable decrease (P<0.001) compared with Group IV (24.94% and 49.13%, respectively). There was a significant reduction (P<0.05) in atherogenic index in Groups III compared with Group IV.
These results clearly suggested that BBR could be effective in reducing liver PAP, lipid abnormality, liver triglyceride and lateral side effects of hyperlipidemia.
PMCID: PMC4025298  PMID: 25183123
Atherogenic index; Flavonoid; Fatty liver; Lipid profile; Lipogenic diet; Oxidative stress
15.  The Ameliorative Effect of Zingiber officinale in Diabetic Nephropathy 
PMCID: PMC4082505  PMID: 25031845
Diabetic Nephropathies; Ginger; Renoprotection
17.  Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants 
Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented.
PMCID: PMC4115353  PMID: 25097610
Antioxidant; hypertension; oxidative stress
18.  Ameliorative effect of melatonin against contrast media induced renal tubular cell injury 
Background and Objective: Reactive oxygen species (ROS) is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against the nephrotoxicity of contrast media.
Methods: In an experimental study 40 adult male Wistar rats were randomly divided into four equal groups including: 1) Control group (No drug), 2) Contrast media group (10 ml/kg iodixanol i.v. single dose), 3) Contrast media and melatonin (first 10 ml/kg iodixanol then 10 ml/kg/day melatonin by i.p. injection on days 3, 4 and 5) and 4) Contrast media and melatonin pretreatment group (melatonin 10 ml/ kg/day by i.p. injection on 1, 2 and 3 days, then 10 ml/kg iodixanol by i.v. injection on third day. The blood creatinine and BUN as well as the histological changes were evaluated for severity of renal injury (degeneration, vacuolization of tubular renal cells, dilatation of tubular lumen and presence of debris in the lumens), by scoring from one to four.
Results: Contrast media significantly increased the creatinine and BUN and renal injury (p<0.05). Melatonin prevented and reversed the injury induced by contrast media (P<0.05). Pretreatment with melatonin reduced the renal injury induced by contrast media (P<0.05).
Conclusion: Melatonin is an effective drug to prevent contrast–induced renal injury. Therefore its usage (especially pretreatment) might be beneficial in patients who are planning to use contrast media agents.
PMCID: PMC3998990  PMID: 24772123
Contrast-induced nephropathy; Contrast media; Iodixanol; Melatonin; Reactive oxygen species; Renal failure
19.  Effects of Ferulago angulata Extract on Serum Lipids and Lipid Peroxidation 
Background. Nowadays, herbs they are considered to be the main source of effective drugs for lowering serum lipids and lipid peroxidation. The present experimental animal study aimed to assess the impact of Ferulago angulata on serum lipid profiles, and on levels of lipid peroxidation. Methods. Fifty male Wistar rats, weighing 250–300 g, were randomly divided into five equal groups (ten rats in each). The rat groups received different diets as follows: Group I: fat-rich diet; Group II: fat-rich diet plus hydroalcoholic extracts of Ferulago angulata at a dose of 400 mg/kg; Group III: fat-rich diet plus hydroalcoholic extracts of Ferulago angulata at a dose of 600 mg/kg; Group IV: fat-rich diet plus atorvastatin; Group V: common stock diet. The levels of serum glucose and lipids and the atherogenic index were measured. In addition, malondialdehyde (MDA), thiol oxidation, carbonyl concentrations, C-reactive proteins, and antioxidant capacity were evaluated in each group of rats. Results. Interestingly, by adding a hydroalcoholic extract of Ferulago angulata to the high-fat diet, the levels of total cholesterol and low-density lipoproteins (LDL) in the high-fat diet rats were both significantly reduced. This result was considerably greater compared to when atorvastatin was added as an antilipid drug. The beneficial effects of the Ferulago angulata extract on lowering the level of triglycerides was observed only when a high dosage of this plant extraction was added to a high fat diet. Furthermore, the level of malondialdehyde, was significantly affected by the use of the plant extract in a high-fat diet, compared with a normal regimen or high-fat diet alone. Conclusion. Administration of a hydroalcoholic extract of Ferulago angulata can reduce serum levels of total cholesterol, triglycerides, and LDL. It can also inhibit lipid peroxidation.
PMCID: PMC3953577  PMID: 24707310
20.  A Double Blind Clinical Trial on the Efficacy of Honey Drop in Vernal Keratoconjunctivitis 
Purpose. This trial was designed to evaluate the efficacy and safety of topical honey eye drops in patients with diagnosed VKC. Methods. This clinical trial was conducted on 60 patients with diagnosed VKC. The patients were selected and randomly allocated between two groups of 30. Patients in two groups received honey eye drop (60% in artificial tear) or placebo, other than cromolyn and fluorometholone 1% eye drops, to be used topically in each eye, four times per day. The patients were examined with slit lamp and torch at baseline and the follow-up visits on the 1st, 3rd, and 6th months of the study for redness, limbal papillae, and intraocular pressure. Results. Out of 60 patients who completed the study, 19 patients (31.7%) were female. There was significant increase in eye pressure and reduction in redness as well as limbal papillae, following the consumption of the honey drop in honey group compared to placebo control group (P < 0.05). At the end of trial, one patient in honey group and 7 ones in placebo group had limbal papillae (P < 0.05). Conclusion. Topical honey eye drops, when used along with Cromolyn and Fluorometholone eye drops, might be beneficial for the treatment of VKC.
PMCID: PMC3953621  PMID: 24707307
22.  Impact of oral vitamin D (cholecalciferol) replacement therapy on blood pressure in type 2 diabetes patients; a randomized, double-blind, placebo controlled clinical trial 
Journal of Nephropathology  2013;3(1):29-33.
Background: Vitamin D is an important mediator of calcium metabolism. It has also been implicated as a potential contributor to the pathophysiology of various extra-skeletal conditions, consisting hypertension, renal disease, and insulin resistance.Objectives: The primary objective of this study was to determine whether oral vitamin D (cholecalciferol) supplementation can lead to improvement of blood pressure in type 2 diabetes patients.
Patients and Methods: This study was a double blind clinical trial conducted on 60 type 2 diabetes mellitus patients. Exclusion criteria were taking calcium, vitamin D supplements or any drugs effecting calcium and vitamin D metabolism in the past 6 months. Patients were administered weekly vitamin D supplementation (50000 units) for 12 weeks. Serum 25-Hydroxy vitamin D [25(OH)D] level was measured with ELISA method.
Results: Five patients (8.3%) had vitamin D deficiency, 27 (45%) had insufficient levels of vitamin D and in 28 (45%) patients vitamin D level was within normal limits. The means of systolic blood pressure (BP) and diastolic BP in patients before intervention were 121 and 80.5 mmHg; after intervention they were 110 and 76.3 mmHg, respectively. After intervention, systolic and diastolic blood pressure levels were significantly less than control group (p< 0.01).
Conclusions: In this study we found that weekly vitamin D supplementation (cholecalciferol; 50,000 units for 12 weeks) had beneficial effect on the level of blood pressure in type 2 diabetic patients. Thus, oral vitamin D may help in improvement of hypertension in these patients.
PMCID: PMC3956905  PMID: 24644541
Type 2 diabetes patients; Vitamin D; Hypertension
23.  Impact of Momordica charantia extract on kidney function and structure in mice 
Journal of Nephropathology  2014;3(1):35-40.
Background: Bitter Melon (BM) is known for its hypoglycemic effect and is commonly used in populations.
Objectives: This study examined the effects and safety of bitter melon fruit in laboratory mice.
Materials and Methods: In this experimental study 70 male mice (25-30 gr) were randomly divided into 7 groups. The mice were injected intraperitoneally with single doses of 0, 100, 500, 1000, 2000 and 4000 mg/kg and multiple doses 500 mg/kg daily for 7 days. The mice were then observed for 72 hours before sacrificing. Immediately kidneys were taken out for histological examinations. Tubular cell vacuolization and flattening as well as hyaline casts, debris and dilatation of tubular lumen were the morphologic lesions which were assessed with scores from 0 to 4, while zero score addressed normal renal tissue. Serum samples were assayed for kidney function (creatinine; Cr and Blood Urea Nitrogen; BUN). Blood and bitter melon antioxidant activities were measured, too. Data were analyzed with Stata software (Stata Corp. 2011. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP)using ANOVA and Bonferroni tests.
Results: All single dose groups showed normal behavior after the dosing and no statistical changes were observed in blood parameters (p>0.05). Histological examinations revealed normal organ structures, however, the group treated for 7 days showed statistically a significant change in BUN (p=0.002) and a borderline significance in Cr (p=0.051).
Conclusions: Administration of up to 4000 mg/kg did not have any effect on the mice kidney function and histology, however chronic administration were nephrotoxic. More studies with different dosage regimens are suggested.
PMCID: PMC3956906  PMID: 24644542
Bitter Melon; Nephrotoxicity; Momordica charantia
25.  Nephrotoxicity and hepatotoxicity evaluation of Crocus sativus stigmas in neonates of nursing mice  
Journal of Nephropathology  2014;3(2):81-85.
Background: Crocus sativus, known as saffron crocus, is best known for the spice saffron. Saffron use spans more than 3500 years, however, its toxicity on neonates during lactation has not yet evaluated.
Objectives: This study was aimed to examine the acute toxicity of saffron on adult mice and its nephrotoxicity and hepatotoxicity on neonates of lactating mothers that used saffron during lactation.
Materials and Methods: In this experimental study, following acute toxicity evaluation, 32 pregnant mice were randomly designated into four equal groups. Following delivery, the mothers of groups 1 to 4 were administered orally (by gavage) normal saline (control group), 500, 1000 or 2000 mg/kg/day of saffron for three weeks, respectively. The newborn’s kidney and liver parameters were assessed at the end of the study for possible nephrotoxicity and hepatotoxicity evaluation. The kidney and liver tissue samples of newborns were histopathologically studied after staining with Hematoxylin & Eosin. Data were analyzed using ANOVA and Scheffe’s tests
Results: The LD50 value of saffron was calculated to be 4120±556 mg/kg in mice. To evaluate lactating toxicity, saffron was administered orally to the mothers once daily for 21 days, after delivery, during lactating period. Saffron increased serum urea nitrogen (p< 0.05). Histological studies indicated that saffron did not have any toxic effect on liver, however, histopathology changes were seen in the kidney of neonates.
Conclusions: From the results of present study, it might be concluded that saffron is a nearly safe spice, however, nursing mothers should avoid high doses of this spice.
PMCID: PMC3999588  PMID: 24772401
Crocus sativus; Saffron; Acute toxicity; Subacute toxicity

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