Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.

BACKGROUND: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Histological and biochemical effects of dexmedetomidine on liver during an inflammatory bowel disease.

Inflammation in the liver is an extraintestinal manifestation that is frequently seen during inflammatory bowel diseases (IBD). The authors investigated histopathologycal, ultrastructural and antioxidant effects of dexmedetomidine (Dex) on liver during trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease. Thirty-two BALB/c mice were divided (n = 8) as follows: control; Dex (dexmedetomidine) (30 µg/kg) for 6 days; TNBS 150 µL, TNBS + ethanol (50% w/v) intrarectally; TNBS + Dex. The histopathological and ultrastructural changes were evaluated. The levels of malondialdehyde (MDA), activity of antioxidant enzymes (GPx and SOD) were measured in liver tissue. Induction of colitis induced histopathological and ultrastructural changes of damage in liver. Those changes were markedly reduced in the TNBS + Dex group and that reduction was even significant in comparison to the TNBS group. MDA levels were significantly higher in the TNBS group and dexmedetomidine significantly elevated SOD levels in the TNBS + Dex group. These results suggest that the administration of dexmedetomidine reduces the histopathological and ultrastructural damage and increases the defense capacity against oxidative damage on liver in this IBD mice model.

Study of the neuroprotective effect of ginseng on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in experimental diffuse head trauma.

BACKGROUND: The purpose of our study was to investigate the effect of ginseng on antioxidant enzyme levels in brain damage following experimental diffuse head trauma in rats. The neuroprotective effect of ginseng was also studied. METHODS: In this study, rats were divided into four groups, and the rats in group 1 received no intervention. In group 2, the rats were administered 50 mg/kg ginseng, injected intraperitoneally at 1, 24 and 48 h, and the effect of ginseng on normal tissues was studied. No drugs were administered to the rats in group 3 who had previously experienced diffuse head trauma using Feeney's falling weight method. In group 4, rats underwent Feeney's falling weight method, leading to diffuse head trauma, and they were given 50 mg/kg ginseng intraperitoneally 1, 24 and 48 h after head trauma. Rats were killed 72 h after head trauma and their brain tissues extracted for histopathological and biochemical studies. RESULTS: Histopathological study of brain cross sections in the trauma group demonstrated neurons in the trauma region and surrounding area, which generally had a dark-colored eosinophilic cytoplasm and a pyknotic nucleus, while the nuclei of neurons were located peripherally. However, brain cross sections in group 4 from rats given ginseng after head trauma showed fewer neurons with eosinophilic cytoplasm, pyknotic and peripheral nuclei in the trauma region and surrounding area. No statistically significant difference in the tissue SOD level was observed; however, the GSH Px level in group 4 was significantly reduced compared to that in group 3. CONCLUSIONS: After affecting the GSH Px level and reducing histopathological scores, ginseng was found to display antioxidant and neuroprotective activity.

Beneficial effects of montelukast against cisplatin-induced acute renal damage in rats.

OBJECTIVE: In this study, the therapeutic and protective effects of montelukast against cisplatin (CP)-induced acute renal damage were investigated. MATERIALS AND METHODS: Thirty-five female rats were divided into five groups as follows: (1) control, (2) montelukast (10 mg/kg daily for 10 days per-oral (p.o.), (3) CP (single dose 7 mg/kg intraperitoneally (i.p.)), (4) CP + montelukast (10 mg/kg daily for 10 days p.o., after 3 days of the injection of CP), (5) montelukast (10 mg/kg daily for 10 days p.o.) + CP (single dose 7 mg/kg i.p., after the last dose of montelukast). At the end of the experiment, malondialdehyde (MDA), a lipid peroxidation product, myeloperoxidase (MPO), and reduced glutathione (GSH) levels were determined in the renal tissue. Also, blood urea nitrogen (BUN) and creatinine (Cr) levels were assayed from the trunk blood samples. RESULTS: CP treatment caused a significant elevation of MDA, MPO, BUN, and Cr levels when compared with the control group. Also, GSH levels were found to be reduced due to the CP treatment. Montelukast administration after CP injection ameliorated all of these parameters. Our histopathological findings (marked swelling of epithelial cells, tubular dilatation, tubular desquamation, and loss of brush border in the kidney) were consistent with the biochemical results. CONCLUSION: Montelukast treatment after CP injection exerted therapeutic effects against CP-induced acute kidney damage.

Effects of third generation mobile phone-emitted electromagnetic radiation on oxidative stress parameters in eye tissue and blood of rats.

PURPOSE: To investigate the effects of electromagnetic radiation (EMR) emitted by a third generation (3G) mobile phone on the antioxidant and oxidative stress parameters in eye tissue and blood of rats. METHODS: Eighteen Wistar albino rats were randomly assigned into two groups: Group I (n = 9) received a standardized a daily dose of 3G mobile phone EMR for 20 days, and Group II served as the control group (n = 9), receiving no exposure to EMR. Glutathione peroxidase (GSH-Px) and catalase (CAT) levels were measured in eye tissues; in addition, malondialdehyde (MDA) and reduced GSH levels were measured in blood. RESULTS: There was no significant difference between groups in GSH-Px (p = 0.99) and CAT (p = 0.18) activity in eye tissue. There was no significant difference between groups in MDA (p = 0.69) and GSH levels (p = 0.83) in blood. CONCLUSIONS: The results of this study suggest that under a short period of exposure, 3G mobile phone radiation does not lead to harmful effects on eye tissue and blood in rats.

Unilateral Ectopic Kidney in the Pelvis and Right Undescended Testicle: A Case Report.

Urinary system anomalies are cases that can be encountered in the clinic. In the anatomy laboratory, we observed that a different vessel was separated from the aortic bifurcation during routine dissection. As a result of the vascular follow-up, we determined that the male cadaver had a pelvic localized ectopic kidney. As a result of the vascularization, we found that there is an ectopic kidney with pelvic location in the male cadaver. One of the most common forms of congenital renal ectopia is pelvic localized ectopic kidney. When the dissection was detailed, the right undescended testicle accompanying the right ectopic kidney was detected. In conclusion we are of the opinion that knowing such anomalies and variations will guide physicians before surgical procedures.

Effects of Acute Moderate and Strenuous Exercise Bouts on IL-17 Production and Inflammatory Response in Trained Rats.

In this study, we aimed to compare the effects of a single bout of acute moderate and strenuous running exercise on the production of interleukin-17 (IL-17), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra) and inflammatory response of skeletal muscles in regularly trained rats. Eight week old rats were trained by treadmill running 5 days per week for 13 weeks at the durations of 30 min (moderate) and 60 min (strenuous). Two days after the last training session, the animals were subjected to a single bout of moderate or strenuous exercise and serum samples were analyzed for IL-17, IL-6, IL-1ra levels and myeloperoxidase (MPO) activity of gastrocnemius muscle were determined. IL-17 level significantly increased in strenuous exercise group when compared to that of sedentary controls (p < 0.01), On the other hand, only in the moderate exercise group, there was a negative correlation between IL-6 and IL-17 levels (r = - 0.857 and p = 0.014). In conclusion, acute single bout of strenuous exercise increased IL-17 production in trained rats and, this cytokine may be involved in inflammatory process of skeletal muscles. Key pointsA single bout of acute strenuous running exercise markedly elevated IL-17 production.This preliminary result should be supported by forthcoming studies that investigate the role of IL-17 in acute inflammatory process of skeletal muscle.

Effects of ciprofloxacin and quercetin on fetal brain development: a biochemical and histopathological study.

PURPOSE: Teratogens cause birth defects and malformations while human development is being completed. In pregnancy, urinary tract infection (UTI) is a common health problem caused by bacteria. The fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin can treat various types of bacterial infections successfully. The aim of this study is to determine whether the use of ciprofloxacin during pregnancy causes oxidative stress on brain tissues of the fetus, and whether quercetin contributes to prevent this damage if stress has already occurred. MATERIALS AND METHODS: In our study, 22 young female Wistar albino rats weighing 250 g were used. Rats were mated overnight in separate plastic cages. Female rats were regarded as pregnant when a vaginal plug was observed, and these were divided into four groups of control, ciprofloxacin, quercetin, and cipro + quercetin. Two daily i.p. 20 mg/kg doses of ciprofloxacin were administered to ciprofloxacin group between 7 and 17 d of pregnancy. Throughout the study, daily (20 d) 20 mg/kg quercetin was dissolved in corn oil and administered to the quercetin group by oral gavage. Rats were fed ad libitum throughout the study. Fetuses were taken by C-section on the 20th day of pregnancy. Thereafter, the brain tissues were subjected to histological assessments and biochemical analyzes. RESULTS: The experimental groups were compared with the control group; ciprofloxacin affected fetal development, especially caused damage to neurons in brain tissue and cause hemorrhagic defects. And also, it was determined that many parameters were affected such as antioxidant parameters, enzyme levels and levels of malondialdehyde (MDA) (a marker of lipid peroxidation). Quercetin is a member of flavonoid with strong antioxidant properties, and our results indicate that the use of ciprofloxacin in pregnancy can result damage to fetal brain tissue. CONCLUSIONS: Unlike these results when some parameters are evaluated it is understood that this harmful effects suppressed by quercetin.

Mechanisms of Alzheimer's Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors.

The characteristic features of Alzheimer's disease (AD) are the appearance of extracellular amyloid-beta (Aß) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid ß-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aß and NMDA receptors. Aß-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.

Protective Effect of Quercetin Against Oxidative Stress-induced Toxicity Associated With Doxorubicin and Cyclophosphamide in Rat Kidney and Liver Tissue.

INTRODUCTION: Doxorubicin and cyclophosphamide are widely used anticancer drugs with substantial toxicity in noncancerous tissue resulting from oxidative damage. Quercetin is a potent antioxidant compound. We hypothesized that quercetin administration would ameliorate the toxic effects of doxorubicin and cyclophosphamide prior to pregnancy. MATERIALS AND METHODS: Cyclophosphamide, 27 mg/kg, and doxorubicin, 1.8 mg/kg, were administered to rats as intraperitoneal doses once every 3 weeks for a total of 10 weeks with or without concurrent treatment with quercetin, 10 mg/kg/d. Oxidative stress parameters were evaluated in maternal kidney and liver tissues after gestation. RESULTS: Doxorubicin was associated with elevated kidney tissue malondialdehyde relative to the controls and quercetin only treatment (P < .05). Both cyclophosphamide and doxorubicin were associated with elevated malondialdehyde levels in the liver tissue (P < .05). Doxorubicin treatment was associated with decreased liver glutathione peroxidase (P < .05). Quercetin treatment suppressed the accumulation of malondialdehyde and increased glutathione peroxidase levels during doxorubicin and cyclophosphamide treatment (P <.05) Conclusions. Treatment with quercetin in patients receiving doxorubicin and cyclophosphamide results in therapeutic restoration of homeostatic expression of the antioxidant parameters, reducing oxidative damage to the liver and kidney.

Biochemical investigation of the toxic effects of acrylamide administration during pregnancy on the liver of mother and fetus and the protective role of vitamin E.

OBJECTIVES: To investigate the toxic effects occurring in the liver tissues of the pregnant rats and the fetuses, which are administered acrylamide and vitamin E as a protector during pregnancy. MATERIALS AND METHODS: This research was conducted with the permission of Laboratory Animals Ethical Board of Inonu University Faculty of Medicine. Forty rats, of which their pregnancy is validated via vaginal smear, were distributed into five different groups. On the 20th day of pregnancy, pregnant rats and fetuses are decapitated. Malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS) and xanthine oxidase (XO) levels were measured in the liver samples taken from mother and fetuses. RESULTS: It was detected that acrylamide administered during pregnancy increased MDA, TOS, XO levels statistically significantly and decreased the GSH level (p ≤ 0.05) in the pregnant rat liver tissue when compared to all other groups. In the vitamin E administered group; GSH, TAS levels significantly increased statistically and TOS and XO levels dropped to levels of the control group (p ≤ 0.05), in comparison to all other groups. Among all groups, no biochemical changes were observed in the fetus liver tissue (p > 0.05). CONCLUSION: The liver of pregnant rats functions as a protective pre-filter by detoxifying acrylamide effectively and the acrylamide that reaches fetus liver is detoxified by the cytochrome P-450 system of the fetus liver. To be able to figure out the biochemical mechanism, more advanced studies are needed.

Effects of phenytoin and lamotrigine treatment on serum BDNF levels in offsprings of epileptic rats.

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Low BDNF levels have been reported in brains and serums of patients with psychotic disorders. In the present study, we investigated the effects of antiepileptic drugs on BDNF in developing rats. Pregnant rats were treated with phenytoin (PHT), lamotrigine (LTG) and folic acid for long-term, all through their gestational periods. Experimental epilepsy (EE) model was applied in pregnant rats. Epileptic seizures were determined with electroencephalography. After birth, serum BDNF levels were measured in 136 newborn rats on postnatal day (PND) 21 and postnatal day 38. In postnatal day 21, serum BDNF levels of experimental epilepsy group were significantly lower compared with PHT group. This decrease is statistically significant. Serum BDNF levels increased in the group LTG. This increase compared with LTG+EE group was statistically significant. In the folic acid (FA) group, levels of serum BDNF decreased statistically significantly compared to the PHT group. On postnatal day 38, no significant differences were found among the groups for serum BDNF levels. We concluded that, the passed seizures during pregnancy adversely affect fetal brain development, lowering of serum BDNF levels. PHT use during pregnancy prevents seizure-induced injury by increasing the levels of BDNF. About the increase level of BDNF, LTG is much less effective than PHT, the positive effect of folic acid on serum BDNF levels was not observed. LTG increase in BDNF is much less effective than PHT, folic acid did not show a positive effect on serum BDNF levels. Epilepsy affects fetal brain development during gestation in pregnant rats, therefore anti-epileptic therapy should be continued during pregnancy.

Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats.

AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), P = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, P < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; P = 0.001, P = 0.001 and P < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) µmol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) µmol/g and 61.46 (58.27-67.75) U/g, P < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) µmol/g and 69.22 (61.13-100.88) U/g, P < 0.05 and P < 0.01 vs model group respectively]. CONCLUSION: MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity.