Hydrogen Peroxide Induced Oxidative Damage on Mineral Density and Mechanical Properties of Bone

ABSTRACT Hydrogen peroxide is a common reactive oxygen species involved in the catalytic mechanism though it is toxic to cells due to its oxidative nature. This work investigates the effects of hydrogen peroxide induced oxidative damage on bone mineral density and mechanical properties of bone which is primarily a composite material composed primarily of collagen fibers and biominerals. Sheep leg bones were exposed to hydrogen peroxide for a week. Bone mineral density was measured by using dual energy X-ray absorptiometry. Compressive modulus tests were applied to bone in order to determine mechanical properties. Our study shows that the hydrogen peroxide induced oxidative stress has negative effects on bone mineral density and stiffness. We observed higher control curve slopes than that of hydrogen peroxide curves which account for lesser stiffness values in the exposed tissue (p<0.05).

Hydrogen peroxide induced oxidative damage on mechanical properties of the articular cartilage.

Articular cartilage has unique mechanical and physicochemical properties which are responsible for its load carrying capabilities. This work investigates the effects of hydrogen peroxide induced oxidative damage on mechanical properties of articular cartilage. Bovine articular cartilage was exposed to hydrogen peroxide for a week. Dynamic and static mechanical tests applied to calculate articular cartilage compressive modulus. We observed higher control curve slopes than that of hydrogen peroxide curves which account for lesser stiffness values in the exposed articular cartilage. For the instantaneous experiments, results were statistically significant (p = 0.01, p < 0.05). Here report that hydrogen peroxide induced oxidative damage causes reduction in the stiffness of the articular cartilage.

The effect of learning styles and study behavior on success of preclinical students in pharmacology.

OBJECTIVES: To evaluate the effect of learning styles and study behaviors on preclinical medical students' pharmacology exam scores in a non-Western setting. MATERIALS AND METHODS: Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success. RESULTS: Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender. CONCLUSIONS: Preclinical medical students' study behaviors are independent predictive factors for short-term pharmacology success.

Response surface methodology for the modelling of 85Sr adsorption on zeolite 3A and pumice.

The adsorption of 85Sr from aqueous solutions on to zeolite 3A and three types of pumice materials (i.e. Kayseri, Isparta and Nevsehir) was investigated in this study. Experiments with radioactive 85Sr were performed to test the sorption ability of the sorbents to remove this radioisotope from liquid radioactive wastes. The influence of sorbent dosage and initial activity of feed solution on the decontamination factor were analysed and optimized by means of response surface methodology. The parameters of the experiments, namely temperature, pH, time, stirring efficiency, were selected in preliminary tests. The experimental results showed that the most efficient pumice sorbent for 85Sr is Isparta, for which a maximal decontamination factor of 76.92 was obtained by using the sorbent dosage of 0.5% w/v. However, the commercial zeolite 3A was 2.71-fold more efficient than Isparta pumice for decontamination of strontium radioactive solutions. Isparta pumice is a low-cost natural sorbent, and its ability to effectively bind strontium radioisotope from water solutions suggests that this material has further applications for radioactive waste treatment.

Effects of misoprostol on cisplatin-induced renal damage in rats.

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CP's side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.

Effects of aspirin and nimesulide on tissue damage in diabetic rats.

This study was designed to compare the effect of Aspirin (AS) and Nimesulide (NM) on renal failure and vascular disorder in streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups; control, diabetic rats, diabetic rats plus AS and diabetic rats plus NM, which are COX inhibitors. The renal and aorta tissues morphology were investigated by light microscopy. Trunk blood was also obtained to determine plasma lipid peroxidation product malondialdehyde (MDA) and plasma activity of antioxidant enzymes. MDA levels were increased in the diabetic rats when compared to the control group. AS and NM administration caused a significant decrease in MDA production. Morphological damage in diabetic rats was severe in the kidney and in the aorta tissue. Treatment of AS reduced these damages, but NM did not exert positive effect on these damages in diabetic rats. As a result, although both AS and NM corrected lipid peroxidation parameters such as MDA via their antioxidant properties, only AS ameliorated pathological alteration in tissues. These findings indicate that there may be another mechanism in beneficial effect of AS in diabetic rats.

Influence of electromagnetic fields on bone fracture in rats: role of CAPE.

OBJECTIVE: To study the effects of radiation emitted by mobile phones on bone strength and caffeic acid phenethyl ester (CAPE) on the changes induced by radiation. METHODS: Forty-eight Sprague-Dawley rats were divided into five groups. Rats in the control group (first group) were left within the experimental setup for 30 min/day for 28 days without radiation exposure. Nine hundred MHz radiation group was broke down into 2 subgroups (group 1/2). Both subgroups were exposed to radiation for 28 days (30 min/day). The next group was also divided into 2 subgroups (group 3/4). Each was exposed to 1800 MHz of radiation for 28 days (30 min/day). The third and fifth groups were also treated with CAPE for 28 days. Treatment groups received ip caffeic acid phenethyl ester (10 micromol/kg per day) before radiation session. Bone fracture was analyzed. RESULTS: Breaking force, bending strength, and total fracture energy decreased in the irradiated groups but increased in the treatment groups. CONCLUSION: Radiation and CAPE can significantly improve bone.

Effects of pentoxifylline on amikacin-induced nephrotoxicity in rats.

The nephrotoxicity of amikacin (AK) was prevented with pentoxifylline (PTX) in a rat model. Rats were received a single injection of AK (1.2 g/kg, i.p.) with or without PTX pretreatment (25 mg/kg, orally). Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) levels. MDA production was found to be higher in AK group. PTX administration caused a significant decrease in MDA production. Morphological damage in rats given AK was severe in the kidney, whereas in rats given AK plus PTX, no histological changes occurred. It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK.

Renal damage in rats induced by myocardial ischemia/reperfusion: Role of nitric oxide.

BACKGROUND: It has been demonstrated that myocardial ischemia/reperfusion (MI/R) causes renal damage. However, the mechanism underlying this damage in kidneys during revascularization of myocardium is unclear. Direct renal ischemia/reperfusion has been implicated in the induction of inducible nitric oxide synthase (iNOS) that leads to increase production of nitric oxide (NO). Recently, excessive production of NO has been found to be involved in causing renal injury by formatting peroxinitrite (ONOO(-)). The aim of this study was to investigate whether NO has a role in this damage, using aminoguanidine (AMG), a known iNOS inhibitor and an antioxidant, in rats undergoing MI/R. METHODS: Male Wistar rats were used for the experiments (n = 7 each group). In the MI/R group, the left coronary artery was occluded for 30 min and then reperfused for 120 min; the same procedure was used for the AMG group, with the additional step of AMG (200 mg/kg) administered 10 min prior to ischemia. A control group underwent sham operation. At the end of the reperfusion period, all rats were killed and their kidneys removed for biochemical determination and histopathological analysis. RESULTS: Myocardial ischemia/reperfusion in the rat kidney was accompanied by a significant increase in malondialdehyde and NO production, and a decrease in glutathione content. Administration of AMG reduced malondialdehyde and NO production and prevented depletion of glutathione content. These beneficial changes in the biochemical parameters were also associated with parallel changes in histopathological appearance. CONCLUSION: These findings suggest that MI/R plays a causal role in kidney injury and AMG exerts renal-protective effects, probably by inhibiting NO production and antioxidant activities.

Ameliorating role of caffeic acid phenethyl ester (CAPE) against isoniazid-induced oxidative damage in red blood cells.

Isoniazid (INH) still remains a first-line drug both for treatment and prophylaxis of tuberculosis, but various organs toxicity frequently develops in patients receiving this drug. We aimed to investigate possible toxic effects of INH on rat red blood cells (RBCs), and to elucidate whether Caffeic acid phenethyl ester (CAPE) prevents a possible toxic effect of INH. Experimental groups were designed as follows: control group, INH group, INH + CAPE group. Compared with the control, the INH caused a significant increase in superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, and a decrease in glutathione peroxidase (GSH-Px) and catalase (CAT), which are recently used to monitor the development and extent of damage due to oxidative stresses. CAPE administration to INH group ameliorated above changes due to INH.

Influence of electromagnetic fields and protective effect of CAPE on bone mineral density in rats.

BACKGROUND: Most mobile phones emit electromagnetic radiation at 900 MHz or 1800 MHz. An electromagnetic field has some biological effects on the behavior of the cell population of bone. The aim of this work is to evaluate the effects of the radiation emitted by mobile phones on bone mineral density (BMD). The effects of caffeic acid phenethyl ester (CAPE) on the radiation-induced changes were also investigated. METHODS: In the study, 48 Sprague Dawley rats were used. Rats were divided into five groups as follows: control, irradiated with 900 MHz, irradiated with 900 MHz and treatment, irradiated with 1800 MHz, irradiated with 1800 MHz and treatment groups. The rats in the control group (first group) were left within the experimental setup during 30 min/day for 28 days without radiation exposure. Nine hundred-MHz radiation group was exposed to irradiate both second and third groups for 28 days (30 min/day); 1800-MHz radiation group was exposed to irradiate both fourth and fifth groups for 28 days (30 min/day). Third and fifth groups were also treated by CAPE for 28 days. Treatment groups received 10 microml/kg/day CAPE i.p. before the irradiation. Bone mineral densities were determined in all groups. RESULTS: BMD was found to be decreased in the irradiated groups and to be increased in the treatment groups. CONCLUSIONS: The changes were not significant (p >0.05).

Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat.

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine the effect of CAPE on cadmium (Cd)-induced hypertension and cardiomyopathy in rats. In particular, nitric oxide (NO) may contribute to the pathophysiology of Cd induced cardiac impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels and nitric oxide (NO, a vasodilator) levels were used as markers Cd-induced cardiac impairment and the success of CAPE treatment. Also, the findings have been supported by the histopathologic evidences. The rats were randomly divided into three experimental groups each (12), as follows: the control group, Cd-treated group (Cd) and Cd plus CAPE-treated group (Cd+CAPE). CdCl(2) in 0.9% NaCl was administrated intraperitoneally (i.p.) with a dose of 1mg/kg/day. CAPE was co-administered i.p. a dose of 10 microM/kg for 15 days. Hypertension was found to be induced by intraperitoneal administration of Cd in a dose of 1mg/kg/day on the measurements taken 15 days later. MDA levels were increased (p<0.001) in cardiac tissue and NO levels were decreased (p<0.05) in serum in the Cd group than those of the control group had. On the other hand, there was a slight difference (increase) in MDA levels in the Cd+CAPE group than the ones in the control group (p<0.003). In addition, MDA levels were decreased and NO levels were increased in the Cd+CAPE group compared with the Cd group (p<0.001, p<0.0001, respectively). As a result, treatment with CAPE significantly reversed the increased lipid peroxidation (LPO) product, MDA, and decreased NO levels in Cd treated animals. In the histopathologic examination, a significant hypertrophy in atrial and ventricular myofibrils was observed in only Cd administered group, in comparison with the control group. There was no statistically significant difference between the CAPE given and control groups by means of atrial and ventricular myofibril diameters. In conclusion, the underlying mechanism of the myocardial hypertrophy may be related to hypertension due to inhibition of NO production in the vessels, and CAPE has a protective effect on Cd-induced hypertension mediated cardiac impairment in the rats.

The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine.

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.

Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats.

Possible effects of long term exposure (6 months) to sodium fluoride (NaF) through drinking water on the morphology and biochemistry of myocardial tissue in second generation adult male rats were investigated. Wistar strain female and male rats were reared until the second generation of rats obtained, during which they were given 1, 10, 50 and 100 mg/L NaF in drinking water. Of the second generation, 28 male rats were divided into four groups and had the same treatment. All the second generation rats were sacrificed and autopsied at the end of the 6 months. In the samples of myocardial tissues, the levels of serum fluoride and the activities of principal antioxidant enzymes were determined, and a histopathological examination was conducted. Significant histopathological changes were found in the myocardial tissue of rats treated with 50 and 100 mg/L NaF. These were myocardial cell necrosis, extensive cytoplasmic vacuole formation, nucleus dissolution in myosits, swollen and clumped myocardial fibers, fibrillolysis, interstitial oedema, small hemorrhagic areas and hyperaemic vessels. Additionally, the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid-reactive substance (TBARS) levels were observed in the myocardial tissues of rats treated with 10 and 50 mg/L NaF. On the other hand, the activities of SOD, GSH-Px, and CAT decreased, but the TBARS levels increased in the myocardial tissues of rats treated with 100 mg/L. The present results revealed that prolonged ingestion of fluoride through drinking water, particularly with high doses, induced significant histopathological and biochemical changes leading to myocardial tissue damage.

Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.

OBJECTIVES: To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. METHODS: The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. RESULTS: The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. CONCLUSIONS: Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.

Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations.

The possible effects of multigenerational administration of sodium fluoride (NaF) via drinking water on lung tissue morphology and biochemistry and body and lung weight were investigated in second-generation adult male rats. For this purpose we selected 45 Albino adult Wistar rats in nine cages, each of which consisted of four females and one male. Twenty-eight pregnant rats were selected for the experiment, divided into four groups of seven rats given 1 (control group), 10, 50 and 100 mg l(-1) NaF in drinking water during the gestation period. After gestation the rats had 165 pups in total. The mothers received fluoridated water during the lactation period and the offspring of the first generation had access to fluoridated water during the suckling period (21 days) and after the weaning period (30 days) until they became mature and at the start of the second part of the experiment. During this time 23 pups died and 79 female and 63 male first-generation rats survived. These first-generation rats were then used to obtain the second-generation offspring in the same manner as before, which were subjected to the same treatments. At the end of 6 months the rats were sacrificed and autopsied. Serum fluoride levels and the activities of principal antioxidant enzymes were determined in lung tissue samples taken from all groups. In addition, the lung tissues were submitted for histopathological examination. Histological findings showed alveolar congestion, alveolar cell hyperplasia and necrosis, prominent alveolar septal vessels, epithelial desquamation and macrophages in the alveolar spaces in the experimental groups. Additionally, there were inflammatory infiltrations in peribronchial, perivascular, intraparenchymal and respiratory tract lumen; intraparenchymal hyperaemic vessels; respiratory epithelial desquamation and proliferation; intraparenchymal thick walled vessels; parenchymal fibrosis; bronchiolitis; pneumonic and focal emphysematous areas. Furthermore, the lung parenchyma was observed to have a distorted appearance with loss of alveolar architecture. These histopathological findings were more pronounced for the rat groups of 50 and 100 mg l(-1) fluoride. No significant histopathological changes were observed in the rats of the control group. The increased activities of superoxide dismutase (SOD) and reduced glutathione peroxidase (GSH-Px) and the decreased activity of catalase (CAT) in the lung tissues with 10 mg l(-1) fluoride might indicate activation of the antioxidant defence mechanism. The decrease in SOD, GSH-Px and CAT activities with 50 and 100 mg l(-1) fluoride and the increase in thiobarbituric acid-reactive substance levels might be related to oxidative damage that occurred in the lung. This multigenerational evaluation of the long-term effect of different doses of fluoride intake through drinking water on lung damage shows that the lung tissues were damaged, there was emphysema and inflammation of lung parenchyma associated with loss of alveolar architecture and the degree of lung damage seemed to correlate with the increased dosage of fluoride. A similar relationship was observed between the degree of lung damage, body and lung weight and serum fluoride levels according to the fluoride dose. Therefore, these results contribute to a better understanding of chronic fluoride toxicity in lung tissue of second-generation rats, especially via drinking water, and the biochemical findings were in agreement with histological observations. In addition, increased fluoride concentration did not affect reproduction or the number of pups dying but the body weight and lung weight ratios were affected by the high dose of fluoride in a dose-related pattern.

The effects of methidathion on liver: role of vitamins E and C.

Methidathion (MD) is one of the most widely used organophosphate insecticides (OPIs) for public health programmes and agricultural purposes. However it causes side effects such as liver disorders. We examined the ameliorating effects of a combination of vitamins E and C against MD induced liver toxicity in rats. MD was given orally with a single dose of 8 mg/kg body weight at 0 h. Vitamin E and vitamin C were injected 30 min after the treatment of MD at doses of 150 mg/kg body weight i.m. and 200 mg/kg body weight i.p., respectively. Liver tissue samples were taken 24 h after the MD administration. In MD treated group, some histopathological changes like infiltration with mononuclear cells at parenchymal tissue, sinusoidal dilatation, focal necrotic areas, granular degeneration and picnotic nuclei in the hepatocytes were observed. The severity of these lesions was reduced by administration of vitamins. It is concluded that MD caused liver damage and single-dose treatment with a combination therapy of vitamins E and C after the administration of MD can reduce the toxic effects of MD on liver tissue of rats.