Evaluating the Proposed Mechanism by Which Atorvastatin Can Protect Renal Tissue against Contrast Media: An Animal study

2019 ◽  
pp. 75-84
Keyword(s):  
Contrast Media ◽  
Kidney Injury ◽  
Saline Group ◽  
Pleiotropic Effect ◽  
Renal Tissue ◽  
Male Rats ◽  
Dependent Manner ◽  
Group 2 ◽  
Dose Dependent ◽  
Media Group

Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.

scholarly journals Thiamethoxam Actara® induced alterations in kidney liver cerebellum and hippocampus of male rats

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hassina Khaldoun-Oularbi ◽  
Noura Bouzid ◽  
Soumia Boukreta ◽  
Chahrazed Makhlouf ◽  
Fariza Derriche ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Male Rats ◽  
Albino Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Neonicotinoid Insecticide ◽  
Group 2 ◽  
Histopathological Studies ◽  
Kidney Liver ◽  
Dose Dependent

Thiamethoxam (TMX), a second-generation neonicotinoid insecticide, is one of the most widely used insecticides in Algeria. The present study assessed the effects of repeated subchronic exposure to the commercial formulation of thiamethoxam (Actara®, 25% WG) in albino male rats. The toxic effects of thiamethoxam (TMX) were studied biochemically and histopathologically. Twenty-eight male albino rats weighing between 226 and 243 g were randomly assigned to four groups. One group served as control, and the other three were served as experimental groups administered a neonicotinoid thiamethoxam (TMX; 26, 39 and 78 mg/kg/day) for 6 weeks. The effects of the insecticide on various biochemical parameters were evaluated at 2, 4 and 6 weeks. Histopathological studies were carried out in the liver, kidney, cerebellum and hippocampus at the end of the experiment. Changes in biochemical parameters glucose, ALT (alanine aminotransferase), AST (aspartate aminotransferase), γGT (gamma-glutamyltransferase) ALP (alkaline phosphatase) urea and creatinine were observed in treated-groups in a dose dependent manner when compared to the control. Histopathological alterations were more intense in male rats from the TMX high dose group than those from group 2 and 3. Based on these results, subchronic oral administration of thiamethoxam altered the biochemical parameters, which correlated with histopathological changes in the liver kidney and brain.

scholarly journals Effects of Phosalone plant pesticide on male fertility by using experiment on Rat

2019 ◽  
Author(s):  
Sorush Niknamian
Keyword(s):  
Male Infertility ◽  
Reproductive Organs ◽  
Elisa Test ◽  
Male Rats ◽  
Control Group ◽  
Dependent Manner ◽  
Organophosphate Insecticide ◽  
Environmental Agents ◽  
Group 2 ◽  
Dose Dependent

Infertility is a major problem for couples and half of the total number of infertilities belong to men, diagnosable in 40% and pathologically undiagnosable in 60% of the cases. Complications of exposure to pesticides is a concern, with a considerable share in male infertility. Phosalone is an organophosphate insecticide usually used to control various types of pests in agriculture. Considering the extensive use of this compound worldwide, the present study examined the effects of environmental agents related to organophosphate on male infertility. To perform the experiments, 16 adult male rats were randomly assigned to four groups with four each. Group 1 received routine rat feed and water as the first control group; Group 2 received low doses (60 mg/kg); Group 3 medium doses (90 mg/kg); and Group 4 high doses of Phosalone (120 mg/kg). After 48 days (end of the treatment), the rats were weighed and anesthetized using ether. Then, their tail of epididymis was removed, and sperm parameters, including number, motility, and viability, were evaluated and compared. Moreover, their reproductive organs were removed and the sexual tissue was processed and underwent histopathological examinations. In addition, in this study, important biochemical parameters in infertility such as the level of sex hormones (LH, FSH, and testosterone) were evaluated using the ELISA test. Results showed that Phosalone decreased sperm motility, viability, and number in a dose-dependent manner. The level of FSH and LH was increased, and that of testosterone was reduced. This increase in FSH and LH must have occurred as the result of reduced testosterone, and all these changes were dependent on the dose of Phosalone. Results of histological studies also revealed that the trend of degeneration in the tissues of testes, epididymis, and seminal vesicle was completely dose-dependent. Phosalone has considerable effects on reproductive indices and can cause serious damage and impose undesirable effects on the number and motility of sperms, causing infertility by altering the concentration of hormones

Evaluation of diuretic and antioxidant properties in aqueous bark and fruit extracts of pine

2020 ◽  
Vol 17 ◽  
Author(s):  
Hadi Shariati ◽  
Mohammad Hassanpour ◽  
Gholamreza Sharifzadeh ◽  
Asghar Zarban ◽  
Saeed Samarghandian ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Phenolic Content ◽  
Antioxidant Properties ◽  
Pine Bark ◽  
Male Rats ◽  
Total Phenolic ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Antioxidant Power ◽  
Dose Dependent

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.

scholarly journals Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Alian Désiré Afagnigni ◽  
Maximilienne Ascension Nyegue ◽  
Chantal Florentine Ndoye Foe ◽  
Youchahou Njankouo Ndam ◽  
Frédéric Nico Njayou ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Leaf Extract ◽  
Shigella Flexneri ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Subacute Toxicity ◽  
Antidiarrheal Activity ◽  
Dose Dependent ◽  
Ethanolic Leaf Extract

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p<0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p<0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

scholarly journals The Effect of the mGlu8 Receptor Agonist, S-3,4-DCPG on Acquisition and Expression of Morphine-induced Conditioned Place Preference in Male rats

2021 ◽  
Author(s):  
Nazanin Kahvandi ◽  
Zahra Ebrahimi ◽  
Seyed Asaad Karimi ◽  
Siamak Shahidi ◽  
Iraj Salehi ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Metabotropic Glutamate Receptors ◽  
Preference Test ◽  
Place Preference ◽  
Male Rats ◽  
Dependent Manner ◽  
Metabotropic Glutamate ◽  
Male Wistar Rats ◽  
Dose Dependent

Abstract Background: The nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGlu receptors) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGlu receptors, including mGlu8 receptors, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGlu8 receptor allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3 μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. Results: The results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. Conclusions: The findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and in reward pathway(s). These data suggest that mGlu8 receptor may be involved in conditioned morphine reward.

scholarly journals Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

Effects of central and systemic administration of leptin on neurotransmitter concentrations in specific areas of the hypothalamus

2006 ◽  
Vol 290 (2) ◽  
pp. R306-R312 ◽  
Author(s):  
Kimberly A. Clark ◽  
Sheba M. J. MohanKumar ◽  
Badrinarayanan S. Kasturi ◽  
P. S. MohanKumar
Keyword(s):  
Intraperitoneal Administration ◽  
Ventromedial Hypothalamus ◽  
Systemic Administration ◽  
Male Rats ◽  
Dependent Manner ◽  
Intracerebroventricular Administration ◽  
Dorsal Nucleus ◽  
Intracerebroventricular Injections ◽  
Dose Dependent ◽  
Pituitary Adrenal Axis

Leptin, a hormone produced by adipocytes, has been shown to affect a number of central functions, such as regulation of the hypothalamo-pituitary-adrenal axis, feeding, and body weight regulation. Because hypothalamic monoamines are intricately involved in the regulation of these functions, we hypothesized that leptin may produce its effects by altering the activity of these neurotransmitters. To test this hypothesis, male rats received peripheral (0, 100, or 500 μg ip), or central (0 or 5 μg icv) injections of leptin. The animals were killed 5 h later, and their brains were removed, frozen, and sectioned. Serum was collected to measure leptin and corticosterone by RIA. The paraventricular nucleus (PVN), arcuate nucleus (AN), ventromedial hypothalamus (VMH), dorsomedial dorsal nucleus (DMD), median eminence (ME), and medial preoptic area (MPA) were obtained using Palkovits' microdissection technique, and monoamine concentrations in these areas were determined using HPLC-EC. Intraperitoneal administration of leptin increased serum leptin concentrations in a dose-dependent manner ( P < 0.05). Both intraperitoneal and intracerebroventricular administration of leptin decreased serum corticosterone significantly ( P < 0.05). Norepinephrine (NE) concentration decreased significantly in the PVN, AN, and VMH after both intraperitoneal and intracerebroventricular administration of leptin ( P < 0.05). NE concentrations decreased significantly in the DMN after intracerebroventricular administration of leptin ( P < 0.05). Leptin treatment (both ip and icv) decreased dopamine concentrations significantly in the PVN. Serotonin (5-HT) concentration decreased significantly in the PVN after both intraperitoneal and intracerebroventricular injections of leptin and decreased in the VMH only with intracerebroventricular treatment of leptin. Leptin did not affect any of the monoamines in the ME and MPA. These results indicate that both central and systemic administration of leptin can affect hypothalamic monoamines in a region-specific manner, which, in turn, could mediate many of leptin's central and neuroendocrine effects.

scholarly journals Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition

2020 ◽  
Vol 11 ◽  
Author(s):  
Jingyu Wang ◽  
Xiaodan Yue ◽  
Cheng Meng ◽  
Ziyan Wang ◽  
Xiaofang Jin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Kidney Injury ◽  
Dose Effect ◽  
Dependent Manner ◽  
Tubular Epithelial Cells ◽  
Mtor Inhibition ◽  
Acute Hyperglycemia ◽  
Renal Tubular ◽  
Dose Dependent

AimAcute hyperglycemia is closely related to kidney injury. Oxidative stress activation and notable mitochondria damages were found under acute hyperglycemia treatment in our previous work. In the present study, we explored the dose-effect relationship and the pivotal role of mitophagy in acute hyperglycemia induced tubular injuries.MethodsForty non-diabetic SD rats were randomly divided and treated with different concentrations of hyperglycemia respectively during the 6-h clamp experiment. Renal morphological and functional alterations were detected. Rat renal tubular epithelial cells were treated with different concentrations of glucose for 6 h. Markers and the regulation pathway of mitophagy were analyzed.ResultsSignificant tubular injuries but not glomeruli were observed under both light and electron microscope after acute hyperglycemia treatment, which manifested as enlargement of tubular epithelial cells, disarrangement of epithelial cell labyrinths and swelling of mitochondria. Urinary microalbumin, β2-MG, CysC, NAG, GAL, and NGAL were increased significantly with the increase of blood glucose (P &lt; 0.05). ROS was activated, mitochondrial membrane potential and LC3-II/LC3-I ratio were decreased but P62 and BNIP3L/Nix were increased in hyperglycemia groups (P &lt; 0.05), which were reversed by AMPK activation or mTOR inhibition.ConclusionAcute hyperglycemia causes obvious tubular morphological and functional injuries in a dose-dependent manner. Acute hyperglycemia could inhibit mitophagy through AMPK/mTOR pathway, which would aggravate mitochondria damage and renal tubular impairment.

scholarly journals Evaluation of anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line compared with doxorubicin using MTT test

2018 ◽  
pp. 163-169
Keyword(s):  
Cell Line ◽  
Proliferative Activity ◽  
Mcf7 Cell ◽  
Mevalonate Pathway ◽  
Pleiotropic Effect ◽  
Receptor Protein ◽  
Dependent Manner ◽  
Proliferative Effect ◽  
Mcf7 Cell Line ◽  
Dose Dependent

Statins are effective to lower the cholesterol level and protect against cardiovascular disease. Recent studies showed that statins have pleiotropic effect and can be used to treat many types of diseases like neurodegenerative disorders, stroke, and cancer. Statins inhibit cell proliferation by suppression of mevalonate pathway leading to desregu-lation of cell signal transduction of some membrane receptor protein which is important for gene transcription. This study was done to evaluate the anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line alone and in combination with anathracycline chemotherapy drug (doxo-rubicin) using MTT assay. The results showed that simvastatin and atorvastatin had significant anti-proliferative effect on MCF7 cell line in dose-dependent manner with an IC50 10.10 μM and 12.3 μM respect-tively. Moreover, the combination of atorvastatin and simvastatin with (1 μM) doxorubicin had higher cytotoxic effect with an IC50 = 0.07 μM and 0.05μM respectively than doxoru-bicin alone IC50 = 1.9 μM. In conclusion, simvastatin and atorvastatin had anti-proliferative effect on MCF7 cell line and displayed significant synergism with doxorubicin which will help in enhancing efficacy of doxorubicin and decrease the adverse effect.

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