Probucol Slows the Progression of Cataracts in Streptozotocin-Induced Hyperglycemic Rats

Pharmacology ◽  
2019 ◽  
Vol 103 (3-4) ◽  
pp. 212-219 ◽  
Author(s):  
Kentaro Higashi ◽  
Asami Mori ◽  
Kenji Sakamoto ◽  
Kunio Ishii ◽  
Tsutomu Nakahara

We examined the effect of probucol, an antihyperlipidemic drug with potent antioxidant properties, on cataract formation in streptozotocin (STZ)-induced hyperglycemic rats that were given 5% D-glucose as drinking water. Probucol treatment was initiated immediately after the induction of hyperglycemia was confirmed. Using full horizontal-plane lens images captured with an original digital camera system, the opacity of central region of lens was assessed by measuring the opaque area in the region. Central opacities were detected after 3 weeks of hyperglycemia, and progressed in a time-dependent manner. The majority of STZ-induced hyperglycemic rats developed severe cataracts after 9 weeks of hyperglycemia. Probucol slowed the progression of cataracts in a dose-dependent manner. Levels of sorbitol and protein carbonyls in lenses of STZ-induced hyperglycemic rats were higher than those of control rats. Probucol suppressed the increase in protein carbonyls, but not of sorbitol, in lenses of STZ-induced hyperglycemic rats. Probucol had no significant effect on increases in plasma concentrations of glucose, total cholesterol, and triglyceride observed in STZ-induced hyperglycemic rats. These results suggest that probucol slows the progression of sugar cataracts, independent of its lipid-lowering effects. The beneficial effect of probucol on cataracts is partially attributable to the attenuation of oxidative damage to lens proteins.

Author(s):  
Hadi Shariati ◽  
Mohammad Hassanpour ◽  
Gholamreza Sharifzadeh ◽  
Asghar Zarban ◽  
Saeed Samarghandian ◽  
...  

Objective: The present study has been carried out to evaluate the diuretic and antioxidant properties of pine herb in an animal model. Materials and Methods: 45 adult male rats were randomly divided into nine groups including: groups I (the negative control), groups II (positive control, furosemide 10 mg/kg), groups III to VIII (treatment groups received 100, 200, 400 mg/kg of the aqueous extracts of bark and fruit) and group IX received the combination of aqueous extract of bark (100 mg/kg) and the fruit (100 mg/kg). The urine output, glomerular filtration rate (GFR), electrolytes, urea, and creatinine levels were evaluated . Furthermore, the phenolic content and antioxidant activity of both extracts were also assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and Folin–Ciocalteu methods. Results: The aqueous extracts of the pine bark and fruit increased the urinary output in a dose-dependent manner. The combination of the two extracts compared to the other extracts alone significantly increased the serum potassium level. This study also showed each extract increase creatinine clearance in a dose-dependent manner (p<0.01 and p<0.05). The increase of GFR in the combination group was not significant. The current data showed a significant increase in the total phenolic content in pine bark extract in compared with the fruit extract. Conclusion: The pine bark and fruit can be useful in the prevention and treatment of kidney stones due to the high antioxidant activity.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaojian Gong ◽  
Qiuyan Zhang ◽  
Shuhua Tan

Thein vivoinhibitory effect of r-hirudin variant III (rHV3) on streptozotocin (STZ)-induced diabetic cataracts in rats was investigated. SD-rats were firstly made diabetic by a single intraperitoneal injection of 2% (W/V) STZ (65 mg/kg). Two weeks later, cataract formation was examined by slit lamp microscope, and the cataracted animals were randomly grouped. The animals in the treated groups received rHV3 drops administration to the eyes with various doses. After 4 weeks treatment, the animals were sacrificed to evaluate the biochemical changes of aldose reductase (AR), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in the eye lens. Meanwhile, the cataract progression was monitored by slit lamp microscope. As a result, rHV3 drops treatment significantly increased the activities of SOD and GSH-Px in the lens in a dose-dependent manner, whereas AR activity and MDA level in the lens were dramatically decreased. Also, the morphological observation further confirmed the inhibition of the development of STZ-induced diabetic cataracts by the rHV3 drops treatment. Thus, our data suggest that rHV3 drops are pharmacologically effective for the protection against STZ-induced diabetic cataracts in rats.


Author(s):  
Alby Alphons Baby ◽  
Regi Raphael K

Background of the Study: Strobilanthes hamiltoniana (Steud.) Bosser and Heine (Acanthaceae) is commonly used in the traditional systems of medicine against helminthiasis and spider bite poison. The plant is known as a garden plant, and medicinal properties of this plant are not yet reported.Objectives: The present study gives a first insight of antimicrobial, anthelmintic, and antioxidant properties of S. hamiltoniana leaves.Methods: All the analysis was done according to standard protocols.Results: The ethanol extract of S. hamiltoniana produced significant antibacterial, antifungal, and anthelmintic properties in a dose-dependent manner, which analyses its folk claim.Conclusion: This paper first reporting the medicinal properties of S. hamiltoniana leaves and the further procedures of identification and isolation of active principles is in progress.


2008 ◽  
Vol 198 (1) ◽  
pp. 147-155 ◽  
Author(s):  
D A Zieba ◽  
M Szczesna ◽  
B Klocek-Gorka ◽  
E Molik ◽  
T Misztal ◽  
...  

Recent studies have demonstrated photoperiodic changes in leptin sensitivity of seasonal mammals. Herein, we examined the interaction of season (long days (LD) versus short days (SD)) and recombinant ovine leptin (roleptin) on secretion of melatonin and prolactin (PRL) and on mRNA expression of suppressor of cytokine signaling-3 (SOCS-3) in the medial basal hypothalamus (MBH) in sheep. Twenty-four Polish Longwool ewes, surgically fitted with third ventricle (IIIV) cannulas, were utilized in a replicated switchback design involving 12 ewes per season. Within-season and replicate ewes were assigned randomly to one of three treatments (four ewes/treatment) and infused centrally three times at 0, 1 and 2 h beginning at sunset. Treatments were 1) control, Ringer–Locke buffer; 2) L1, roleptin, 0.5 μg/kg BW; and 3) L2, roleptin, 1.0 μg/kg BW. Jugular blood samples were collected at 15-min intervals beginning immediately before the start of infusions and continued for 6 h. At the end of blood sampling, a washout period of at least 3 days elapsed before ewes were re-randomized and treated with one of the treatments described above (four ewes/treatment). Ewes were then killed and brains were collected for MBH processing. Leptin treatments increased (P<0.001) circulating leptin concentrations compared with controls during both seasons in a dose-dependent manner. Overall, mean plasma concentrations of melatonin were greater (P<0.001) during LD than SD. However, leptin treatments increased melatonin concentrations during SD in a dose-dependent manner and decreased it during LD. Similarly, plasma concentrations of PRL were greater (P<0.001) during LD than SD. However, unlike changes in melatonin, circulating PRL decreased (P<0.001) in response to leptin during LD. Semi-quantitative PCR revealed that leptin increased (P<0.001) SOCS-3 expression in the MBH region during LD in a dose-dependent manner. Data provide evidence that secretion of photoperiodic hormones such as melatonin and PRL are inversely regulated by leptin during SD and LD. However, the increase in expression of SOCS-3 in the MBH during LD compared with SD fails to fully explain these effects.


2017 ◽  
Vol 42 (11) ◽  
pp. 1179-1184 ◽  
Author(s):  
Lin Yan ◽  
Sneha Sundaram ◽  
Forrest H. Nielsen

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 22-22 ◽  
Author(s):  
Joshuaine Toth ◽  
Guanfa Gan ◽  
Joanne van Ryn ◽  
Holly Dursema ◽  
Jennifer Isler ◽  
...  

Abstract Abstract 22 Background: The objective of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran (a small molecule thrombin inhibitor) and its antidote (a humanized Fab against dabigatran) in the monkey and to develop a combined mechanistic mathematical model to describe the data. Methods: There were three groups: control, antidote alone and dabigatran etexilate (DE) + antidote. Rhesus monkeys (n = 2/group) received either 12 mg/kg/day of DE or vehicle orally on Days 1–4, 15–18 and 29–32 with a single IV dose of the antidote administered 90 minutes after DE on Days 4, 18 and 32. Doses of the antidote were 30, 90 or 175 mg/kg, respectively. PK parameters of the antidote and sum dabigatran (dabigatran plus its glucuronides) were determined after measurements of plasma concentrations. Coagulation activity was measured using a diluted thrombin time assay to determine the activity of the unbound sum dabigatran. Results: The PK of the antidote were not affected by dabigatran. Clearance of the antidote was low (0.87 mL/min/kg) and steady-state volume of distribution was small (0.06 L/kg), indicating that the antidote was mostly restricted to plasma. The plasma profile of the antidote was bi-phasic with a short initial phase t1/2 of 0.4 hour (h) and a terminal phase t1/2 of 4.3 h. Immediately after antidote dosing, plasma concentrations of sum dabigatran increased, a consequence of the rapid redistribution of dabigatran and its glucuronides from tissue to plasma due to binding to the antidote. Complete reversal of dabigatran's anticoagulant activity was observed immediately after antidote dosing at all three dose levels, as measured by the diluted thrombin time assay, which indicates that all dabigatran was bound to the antidote. The degree to which this reversal effect was maintained over an extended period (24 h) was dose-dependent. A mechanistic ordinary differential equation model, based on the mass action kinetics for describing the distribution, binding and elimination of dabigatran and its antidote, was developed by combining the PK models for dabigatran and the antidote and adding the binding interaction (1:1 stoichiometry) between the two compounds. The distribution and elimination parameters of the dabigatran-antidote complex were assumed to be the same as those of the antidote, based on similar measured PK parameters of the antidote with and without dabigatran in the monkey. The combined PK/PD model of dabigatran and antidote was able to describe the in vivo PK/PD data observed in monkeys. Conclusion: The dabigatran-specific antidote successfully reversed the anticoagulant activity of dabigatran in the monkey in a dose-dependent manner, and our combined mathematical model accurately describes monkey PK/PD data of sum dabigatran and its antidote. Insights gained from this model will be used to guide model development for clinical trials. Disclosures: Toth: Boehringer Ingelheim: Employment. Gan:Boehringer Ingelheim: Employment. van Ryn:Boehringer Ingelheim: Employment. Dursema:Boehringer Ingelheim: Employment. Isler:Boehringer Ingelheim: Employment. Coble:Boehringer Ingelheim: Employment. Burke:Boehringer Ingelheim: Employment. Lalovic:Boehringer Ingelheim: Employment. Olson:Boehringer Ingelheim: Employment.


2013 ◽  
Vol 781-784 ◽  
pp. 1500-1507
Author(s):  
Zhong Jin ◽  
Qian Liu ◽  
Bao Hua Kong ◽  
Jing Li ◽  
Qian Chen

This experiment was conducted to assess the antioxidant efficacy of Seabuckthorn (Hippophae rhamnoides) leaves extracts (SLE) in raw pork patties during chilled storage at 4 °C for 0-7 days. The pork patties were analyzed periodically for chemical characteristics, such as pH value, colour, thiobarbituric acid-reactive substances value (TBARS), peroxide value (POV) and protein carbonyls content. Compared with the control, SLE treatments significantly decreased the TBARs and POV values and carbonyls formation of pork patties in a dose-dependent manner (P < 0.05), which showed that the SLE significantly inhibited lipid and protein oxidation. The results of this study suggested that the antioxidant activities of seabuckthorn leaves extracts could have great effect on improving the quality characterizes of pork patties and prolong its shelf life.


Author(s):  
Ghasem Majdi Yazdi ◽  
◽  
Gholamhasan Vaezi ◽  
Vida Hojati ◽  
Mohammad Mohammadzadeh ◽  
...  

Introduction: Research has shown that gold nanoparticles (AuNPs) can damage brain tissue physiological processes. Given the antioxidant properties of gingerol (GING), the aim of this study was to determine the protective effect of 6-gingerol on hippocampal levels of brain-derived neurotrophic factor, nerve growth factor, DNA oxidative damage, and the amount of Bax and Bcl-2 Apoptosis indices of rats exposed to AuNPs. Methods: Forty two male Wistar rats were divided into four groups: control (30 days 0.5 ml saline), AuNPs (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml saline), AuNPs+GING 50 (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml density of gingerol 50 mg / kg), AuNPs+GING100 (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml density of gingerol 100 mg / kg). At the end of the treatment period, the hippocampal levels of NGF, BDNF, 8-HodG and Apoptotic indices of Bax and Bcl-2 were assessed through ELISA method. Results: Compared with the AuNPs group, hippocampal levels of BDNF, NGF, and Bcl-2 in rats from AuNPs+GING 50 and AuNPs+GING 100 groups significantly increased depending on the dose of injection. The hippocampal levels of Bax and HOdG-8 significantly decreased in a dose-dependent manner (P < 0.05). Conclusion: According to obtained results, it may be suggested that gingerol improves hippocampal BDNF and NGF levels in rats exposed to AuNPs maybe by reducing apoptosis and oxidative DNA damage.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ganiyu Oboh ◽  
Ayodele J. Akinyemi ◽  
Olasunkanmi S. Omojokun ◽  
Idowu S. Oyeleye

Background. Cola acuminataseed, a commonly used stimulant in Nigeria, has been reportedly used for the management of neurodegenerative diseases in folklore without scientific basis. This study sought to investigate the anticholinesterase and antioxidant properties of aqueous extracts fromC. acuminataseedin vitro.Methodology.The aqueous extract ofC. acuminataseed was prepared (w/v) and its effect on acetylcholinesterase (AChE) and butyrylcholinesterase activities, as well as some prooxidant (FeSO4, sodium nitroprusside (SNP), and quinolinic acid (QA)) induced lipid peroxidation in rat brainin vitro, was investigated.Results.The results revealed thatC. acuminataseed extract inhibited AChE (IC50= 14.6μg/mL) and BChE (IC50= 96.2μg/mL) activities in a dose-dependent manner. Furthermore, incubation of rat’s brain homogenates with some prooxidants caused a significant increaseP<0.05in the brain malondialdehyde (MDA) content and inhibited MDA production dose-dependently and also exhibited further antioxidant properties as typified by their high radicals scavenging and Fe2+chelating abilities.Conclusion.Inhibition of AChE and BChE activities has been the primary treatment method for mild Alzheimer’s disease (AD). Therefore, one possible mechanism through which the seed exerts its neuroprotective properties is by inhibiting cholinesterase activities as well as preventing oxidative-stress-induced neurodegeneration. However, this is a preliminary study with possible physiological implications.


1983 ◽  
Vol 245 (5) ◽  
pp. E431-E442 ◽  
Author(s):  
L. Sjostrom ◽  
Y. Schutz ◽  
F. Gudinchet ◽  
L. Hegnell ◽  
P. G. Pittet ◽  
...  

A test for determination of epinephrine sensitivity has been worked out using six healthy young women. Variables considered were metabolic rate, heart rate, respiratory frequency, blood pressure, blood glucose, plasma insulin, glycerol, free fatty acids, and lactate. After established basal conditions, epinephrine was infused at rates of 0.01, 0.03, and 0.1 microgram X kg fat-free mass-1 X min-1. Most variables responded to epinephrine in a dose-dependent manner. Physiological threshold plasma concentrations of epinephrine ranged from 95 to 250 pg/ml for different variables. Calculated maximal responses ranged from approximately -15% to +900% of basal values and infusion rates giving half-maximal responses from approximately 15 to 190 ng X kg fat-free mass-1 X min-1. On an average, metabolic rate increased by 8, 16, and 29%, respectively, at the three infusion rates, and the maximal metabolic response was calculated to be approximately 35%. The error in determining epinephrine-induced increments in metabolic rate was 7% of the response. As calculated from nonprotein RQ, carbohydrate oxidation increased and lipid oxidation decreased rapidly during the first 10 min of epinephrine infusion. Later, fat oxidation became more important. Results on epinephrine plasma metabolic clearance rate agreed with earlier results in the literature.


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