Nurcan Dursun

Blood pressure relationship to nitric oxide, lipid peroxidation, renal function, and renal blood flow in rats exposed to low lead levels.

The results of experiments designed to show that inhibition of nitric oxide production in rats exposed to low lead levels increases vascular resistance, decreases renal blood flow and glomerular function, and enhances oxidative stress. Forty-five adult male Sprague-Dawley rats were divided into four groups. Group A was used as controls and consisted of rats that received no treatment; group B acted as NO-inhibited controls by receiving l-NAME (NG-nitro-l-arginine methyl ester) as the NO inhibitor; group C was injected intraperitoneally with 8 mg/kg lead acetate for 2 wk; and group D receiving lead acetate plus l-NAME.Compared to healthy controls, significant elevation of the mean (p<0.01), systolic (p<0.04), and diastolic (p<0.01) blood pressures was found in the lead-treated rats. The renal blood flow was 1550±468 blood per unit (bpu) in the controls, 488±220 bpu in the l-NAME controls, 1050±458 bpu in the lead-treated group, and 878±487 bpu in the Pb plus l-NAME group.Low-level lead exposure did not change the urinary flow rate, creatinine clearance, and the creatinine, potassium, phosphorus, glucose, and protein excretion in 24-h urine. In the lead plus NO-inhibited rats, a significant decrease in sodium ion excretion was observed (p<0.01). The NO levels of the lead exposed, l-NAME-treated controls, and l-NAME plus lead-exposed groups are significantly lower compared to untreated control:: p<0.002, p<0.001, and p<0.01, respectively. When compared to untreated controls, the plasma malondialdehyde levels were not significantly different in the lead exposed, lead plus l-NAME, and l-NAME control groups.These results suggest that lead-induced hypertension might be related to a decrease of NO and consequent vasoconstriction, rather than to a decrease of renal blood flow or to decreases in renal sodium.

Role of Thymus Oil in Burn Wound Healing

Thymus oil and its components are becoming increasingly popular as naturally occurring antimicrobial and antioxidant agents. The real importance of thymus on nitric oxide (NO) is unknown. NO is an important mediator in numerous physiologic and pathophysiologic events. Stasis and thrombosis in burn wound can progress as a result of the release of local mediators. The implication of NO in burn injury is not well studied. In this study, we tried to determine the role of burn-induced NO and whether thymus oil plays a protective role after a thermal injury. Rats were divided into five groups. We topically applied thymus oil, olive oil, and silverdin and sulfadiazine on the rats, respectively, during a period of 21 days after they were burned while under anesthesia. The burned control group and nonburned control group did not receive any treatment. The results of this study show that NO was overproduced by thermal injury and decreased during the days after burn injury. The decrease in rats treated with thymus and sulfadiazine was higher than the others. These data indicate that thymus oil may serve as a protective agent to the damaged tissues by decreasing the NO level. Histologic examination results show that the formation of new tissue in rats receiving thymus oil was more than other burned groups, and this finding supports our hypothesis.

The effects of ovariectomy on the mechanical properties of skin in rats

OBJECTIVE After menopause, observable changes occur in the physical characteristics of the human skin. These changes and their responses to various treatments can be assessed with non-invasive in-vivo mechanical tests. However, tests measuring breaking strength and tensile strengths can only be done ex-vivo, they require relatively higher quantities of skin and thus have generally been performed on animals. Mechanical changes in the skin of ovariectomized rats, an appropriate model for the study of postmenopausal period, have not been dealt with in the literature. In this study mechanical characteristics of the skin, such as breaking strength and tensile strength have been tested and studied histologically in ovariectomized rats. METHODS Sixteen rats were divided into two groups, one undergoing ovariectomy and one control group undergoing a sham operation. Three months later, the rats were sacrificed and tensile properties of their back skins were tested with a tensometer and evaluated histologically. RESULTS AND CONCLUSION Breaking strength, tensile strength and the Youngs modulus have increased and the thickness of the subcutis has decreased in ovariectomized rats. This study should be tested by others, because of existence of some conflicts between available knowledge and the results, relating to postmenopausal skin changes.

Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats

OBJECTIVE Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. The present study examined the antioxidant protective effects of carnosine (CAR) on adriamycin-induced cardiac damage in rats. METHODS Female Sprague Dawley rats were divided into four groups. Control (CONT, n=8, saline only i.v.); carnosine (CAR, n=8.10 mg/kg/day, i.v.); adriamycin (ADR, n=10.4 mg/kg four times every 2 days for 8 days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10). Carnosine was given one week before adriamycin treatment and following one week with adriamycin treatment. After measurement of physiological functions, blood samples were collected for biochemical assays. The hearts were excised for hemodynamic study. Comparisons between different groups were made using ANOVA and posthoc Tukey test. RESULTS Adriamycin produced evident cardiac damage revealed by; hemodynamic changes - decreased left ventricular developed pressure (p=0.01), the maximum-minimum rates of change in left ventricular pressure (± dP/dt, p=0.01), electrocardiogram (ECG) changes (elevated ST, decreased R-wave, p=0.001), cardiac injury marker changes (increased creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase), plasma antioxidant enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalase activities, p=0.03) and lipid peroxidation (elevated malondialdehyde, p=0.05) to the control and carnosine groups. Carnosine treatment caused significant attenuation (p=0.05) of cardiac dysfunction induced by adriamycin (CAR+ADR), revealed by normalization of the ventricular function, ECG and biochemical variables. CONCLUSION An increase in oxidative stress, superoxide dismutase, glutathione peroxidase levels, catalase inactivation and cardiac dysfunction induced by adriamycin were prevented by carnosine.

Selenium-mediated cardioprotection against adriamycin-induced mitochondrial damage

Adriamycin (ADR) causes morphological and functional alterations in mitochondrial structure in the heart. The study′s aim was to determine whether there is a protective effect of selenium (Se) on ADR-induced cardiac damage. Rats were divided into four groups: The first group was injected saline intraperitoneally (i.p.) for 21 days; the second group received 4 mg/kg i.p. ADR every alternate day for 8 days; the third group received 50 µg/kg i.p. Se for 21 days; and the fourth received the Se (for 21 days) and ADR (for 8 days) coadministration i.p. Left ventricular functions, electrocardiography parameters, and blood pressures were assessed. Mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, and thioredoxin reductase (TrxR) activity were determined. Total antioxidant (TAS) and oxidant status (TOS) in cytosol, mitochondria of myocytes, and plasma were measured. Left ventricular data demonstrated left ventricular systolic pressure (LVSP) decreased, left ventricular developed pressure (LVDP) decreased, and left ventricular end-diastolic pressure (LVEDP) increased in ADR-treated animals, compared to the control and Se groups. ADR decreased the membrane potential and ATP level in myocyte mitochondria. TrxR activity decreased in the ADR group, compared to the Se group. Cytosolic and mitochondrial TAS decreased and mitochondrial and plasma TOS increased in the ADR group, compared to the control. The coadministration of Se with ADR attenuated left ventricular dysfunction, improved MMP and ATP levels, and prevented oxidative stress by increasing antioxidants (especially TrxR) and decreasing oxidants. We concluded that Se is effective against ADR-induced cardiac damage via the restoration of TAS and TOS, which prevented mitochondrial damage.

Renal effects of long-term leptin infusion and preventive role of losartan treatment in rats

BACKGROUND Leptin has direct and indirect effects on renal pathophysiological characteristics. In the present study, the effects of long-term leptin infusion on the renal hemodynamics, renal excretory functions, and the expression of transforming growth factor-beta (TGF-beta), plasma endothelin-1 (ET-1) levels, and preventive effects of the angiotensin II type 1 receptor antagonist, losartan, on these renal changes were evaluated. METHODS The study was performed by using forty Wistar albino rats. On day 0, osmotic mini-pumps filled with leptin or placebo were intraperitoneally placed under sterile conditions. The rats in Group L (Leptin group, n=15) and Group LL (Leptin-losartan group, n=15) were given recombinant murine leptin at a rate of 250 ng per hour for 28 days. Control rats (Group C, n=10) were administered placebo at the same infusion rate. The rats in Group LL were also administered losartan (10 mg kg(-1) d(-1)) perorally for 28 days. On day 28, the rats were placed in metabolic cages, and the food and water intakes were determined, and the urine was collected for 24 h. At the end of the study, systolic blood pressure (SBP), diastolic blood pressure (DBP) were determined directly from the left femoral artery, and renal blood flow (RBF) was recorded indirectly using a laser Doppler flow module. RESULTS Leptin infusion did not produce any changes in systemic arterial blood pressures and urinary flow rate. The rates of creatinine (Cr), sodium (Na), and protein excretions of the animals infused leptin were significantly increased. The urinary Cr and Na excretions were decreased, while the urinary protein excretion was normalized with the losartan treatment. The rats infused leptin had also higher circulating ET-1 levels. ET-1 levels were also reversed to the normal values with the losartan treatment. Renal TGF-beta1 expression was determined immunohistochemically, and it was more prominent in the renal tubules from the rats treated with leptin. The losartan treatment had no effect on renal TGF-beta1 expression. CONCLUSIONS Our results indicate that pathophysiological increases in plasma leptin concentrations cause enhanced renal Na, Cr and protein excretions, and high circulating ET-1 levels. Na and Cr excretions were decreased, while proteinuria and plasma ET-1 levels were normalized by losartan treatment, suggesting that renin-angiotensin system activation may have a role in leptin induced renal changes. TGF-beta1 may have an important role in leptin induced nephropathy.

Increased sister chromatid exchanges in workers exposed to occupational lead and Zinc

Sister chromatid exchange (SCE) in blood lymphocytes was determined in 32 male workers occupationally exposed to lead (Pb) and zinc (Zn) and in 20 controls matched for age and smoking habits. Exposed workers have higher SCE mean values than control workers (p < 0.01). In exposed persons, blood Pb concentrations were also significantly higher than controls (p < 0.0001), but the difference between Zn levels in the blood of these groups was not found to be significant (p > 0.05). Our results indicate that Pb may be genotoxic and harmful to human health.

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

Abstract Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p < 0.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p < 0.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p < 0.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.

Plasma and erythrocyte lipid peroxide levels in workers with occupational exposure to lead

The plasma and erythrocyte lipid peroxide levels were measured in a group of male subjects occupationally exposed to lead for an average period of 17 yr, and compared to those from an age-matched control group living in the same city in a similar socioeconomical environment.The blood lead and plasma zinc levels were measured by atomic absorption spectroscopy. The plasma and erythrocyte lipid peroxide levels were established by the malondialdehyde determination method. Significant differences were found in the blood lead levels in lead-exposed workers, 15.00±10.15 µg/dL as compared to controls, 2.37±0.89 µg/dL. The plasma (2.67±0.69 µM) and erythrocyte (27.53±6.28 nmol/g Hb) lipid peroxide levels in workers with occupational exposure to lead were significantly higher than controls, 1.23±0.61 µM and 14.35±2.08 nmol/g Hb, respectively. There were no significant differences of the zinc levels in both groups.The blood lead levels had a statistically significant positive correlation with age and with duration of exposure in both groups, but showed no relationship to the corresponding blood zinc levels. The results presented in this study indicate that the increase of plasma and erythrocyte lipid peroxide levels in workers exposed to lead may be related to the lead concentration, age and duration of exposure.

The influence of dietary iron on zinc in rat

The purpose of this study was to clarify the influence of iron on zinc status. The animals were divided into four groups, consisting of five rats in each group. The control group was fed on basal diet with adequate levels of zinc and iron, whereas the experimental group was fed diets containing different levels of iron ad libitum for 15 d. Low levels of iron (LFe) significantly increased the zinc absorption percentage but there was a decrease in high (HFe) and very high iron (VHFe) level groups (p<0.001). The retention percentage changes were found to be parallel to the changes in the absorption percentage curve. It was found that zinc (per total dry tissue) and Zn-65 (per total tissue) increased in the rats fed the LFe, whereas in general they decreased in the rats fed the HFe and VHFe diets. Significant changes were found in the duodenum and liver. Zn-65 (per g wet tissue) significantly increased in the brain and liver in the LFe group, but there was a decrease in the duodenum, ileum, kidney, liver, and brain in the HFe and VHFe groups. Changes in the level of zinc (per g dried tissue) were found to be parallel to the changes in Zn-65 in all the groups. The dietary proportions of iron appear to influence zinc metabolism at the intestinal and cellular transport levels over a given period of time.