Slavimir Veljkovic

Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats

Since gentamicin-induced nephrotoxicity has very important clinical consequences, different potentially therapeutic approaches to prevent or attenuate it have been proposed. Accordingly, this study aimed at determining the possible protective effects of vitamin C against gentamicin-associated acute kidney injury. Experiments were done on 40 adult Wistar rats divided into four groups of 10 animals each. G-group received gentamicin (100 mg/kg) while GVC-group received the same dose of gentamicin and vitamin C (200 mg/kg) by intraperitoneal injections on a daily basis. Animals in VC-group, serving as a positive control, received only vitamin C (200 mg/kg), and those in C-group, serving as a negative control, received saline (1 ml/day), both given intraperitoneally. All groups were treated during 8 consecutive days. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations of kidney were performed by histopathological, morphometrical and biochemical analyses in order to determine potential beneficial effects of vitamin C co-administration with gentamicin. In G-group the proximal convoluted tubules showed cytoplasm vacuolation with dark inclusions in the epithelial cells and coagulation-type necrosis, while in GVC-group necrosis was not observed. The glomerular basement membrane was significantly thickened (p<0.05) in G-group animals than in other groups. Nuclear optical density of the tubular epithelial cells in GVC-group was significantly higher (p<0.05) compared to G-group. Blood urea and serum creatinine concentration were significantly elevated, while potassium concentration was lowered in G-group compared to other groups (p<0.01 for each). Concomitant administration of gentamicin and vitamin C resulted in a significant reduction of morphological and functional kidney alterations.

Glomerular basement membrane alterations induced by gentamicin administration in rats

The widespread therapeutic use of the aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic side effect, which can lead to acute renal failure. This study aimed at examining effects of high, supratherapeutic doses of gentamicin on morphological, structural and functional alterations of the glomerular basement membrane in adult rats. Experiments were done on 30 male Wistar rats, divided into two experimental groups. GM-group (20 rats) received gentamicin at a dose of 100mg/kg intraperitoneally during eight consecutive days. Control or C-group (10 rats) received 1 ml/day saline intraperitoneally. For histological analysis, 5 microm thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. Glomerular basement membrane thickness, glomerular area, major and minor axes, perimeter, diameter, roundness and mean optical density were analyzed. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium and potassium. In GM-group rats, glomeruli were larger and glomerular basement membrane was diffusely and irregularly thickened with neutrophil cell infiltration. Glomerular area, major axis, minor axis, diameter and perimeter were significantly higher in GM-group compared to C-group rats. Opposite to this, glomerular optical density and average roundness were larger in C-group than in gentamicin-treated animals. Our results clearly showed morphological and structural alterations of glomeruli and glomerular basement membrane as well as alterations of proximal tubules in adult rats exposed to high doses of gentamicin.

Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress–associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.

Comparison of the Hypotensive and Bradycardic Activity of Ginkgo, Garlic, and Onion Extracts

The acute effect of ethanol extracts ginkgo (Ginkgo biloba L.), garlic (Allium sativum L.), and onion (Allium cepa L.) on arterial blood pressure (BP), and heart rate (HR) in anesthetized normotensive rats was examined and compared. Arterial BP was registered in the left carotid artery. The data showed that intravenous administration of the extracts produced dose-dependent and reversible hypotensive and bradycardic effects. The most effective in reducing arterial BP and HR is extract of garlic. There were statistically significant differences in bradycardic and hypotensive effects of the garlic and ginkgo extracts.

Protective Effects of Pentoxifylline Treatment on Gentamicin-Induced Nephrotoxicity in Rats

Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. Thus, the present study was undertaken to determine if pentoxifylline could protect the kidney in this experimental model. Thirty male Wistar rats were used. The animals were divided into three groups, each with 10 animals. The GM group of animals was treated daily with gentamicin in a dose of 100 mg/kg for eight days. The GMP group of animals was treated daily with pentoxifylline in a dose of 45 mg/kg and the same dose of gentamicin as the GM group for eight days. The control group received 1 mL/day saline intraperitoneally. For histological analysis, 5 μm-thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. The morphometric parameters included were glomerular area, major and minor axis, perimeter, diameter, roundness, and mean optical density. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium, and potassium. In the GM group of rats, glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear leukocyte infiltration, and coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In the GMP group of rats, glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis of proximal tubules epithelial cells. Blood urea and serum creatinine concentration in the GM group were significantly elevated in comparison with the GMP group, while the potassium level was decreased. The present study indicated that pentoxifylline could provide a marked protective effect against gentamicin-induced acute renal failure, most likely mediated by vascular decongestion.

Comparative Study of Spasmolytic Properties, Antioxidant Activity and Phenolic Content of Arbutus unedo from Montenegro and Greece

Arbutus unedo leaf is used traditionally for gastrointestinal complaints. Ethanol extracts from Arbutus unedo collected in both Montenegro (AuM) and Greece (AuG) were found to decrease the ileal basal tonus, with AuG producing a significantly higher (p < 0.05) reduction in contractile response to acetylcholine. AuM and AuG relaxed 80 mm K+ induced contractions and shifted the Ca++ concentration–response curves to the right, similar to that caused by verapamil, suggesting that the spasmolytic effect was induced through calcium channel inhibition. The antioxidant activity of AuM and AuG and the phenolic content of the extracts and dry plant material were studied, and both extracts were found to possess considerable antioxidant properties. AuG showed a stronger in vitro antioxidative activity in the DPPH assay and in the TBA test. Polyphenol, tannin and flavonoid levels were higher in AuG, supporting the more potent spasmolytic and antioxidative effects, whereas the arbutin content was higher in dry plant material collected in Montenegro. Copyright

The risk of breast, cervical, endometrial and ovarian cancer in oral contraceptive users

INTRODUCTION Oral contraceptives, mainly combined monophasic pills, are widely used by young women who expect their physicians to prescribe them safe drugs which will not harm their health and which will simplify their life. Numerous epidemiologic studies have been performed to determine the relation between oral contraceptive use and the development of neoplasms. BREAST CANCER An increased incidence of breast cancer has occurred simultaneously with the growing use of oral contraceptives. The possibility of a link between the oral contraceptive use and breast cancer has led to intensive research, but studies have provided inconsistent results causing confusion among clinicians. It was noticed that the risk of breast cancer was slightly elevated in current and recent young oral contraceptives users. That finding could be influenced by a detection bias or could be due to the biologic effect of the pills. The absolute number of additional breast cancer cases will be very small because of low baseline incidence of the disease in young women. Oral contraceptives probably promote growth of the already existing cancer, they are probably promoters not initiators of breast cancer. The available data do not provide a conclusive answer that is needed. CERVICAL CANCER Numerous factors may influence the development of cervical cancer. The evidence suggests that current and recent oral contraceptive users have an increased risk of cervical cancer which decline after discontinuation of the application of medication. Oral contraceptives might increase the biological vulnerability of the cervix. Cervical cancer develops slowly over a long time period and can be effectivelv prevented by periodic cervical screening. Fortunately, oral contraceptives do not mask abnormal cervical citology. Conclusions regarding invasive cervical cancer and oral contraceptive use are not definitive but if there is any increased risk, it is low. ENDOMETRIAL CANCER In oral contraceptive users the endometrium is almost under the influence of progestin component which suppresses endometrial mitotic activity and its proliferation. Most epidemiologic studies show that oral contraceptives reduce the risk of endometrial cancer and that this protective effect exists many years after the discontinuation of medication. OVARIAN CANCER It has been long known that the oral contraceptive use causes protective anovulation and reduces the risk of ovarian cancer. This powerful reduction is the best demonstrated major benefit of oral contraception. This protection is especially observed in nulliparous and seems to persist for many years after the discontinuation of medication.

The beneficial biological properties of salicylic acid

Summary Salicylic acid is a phytochemical with beneficial effects on human well-being. Salicylic acid is a phenolic compound and is present in various plants where it has a vital role in protection against pathogenic agents. Natural sources include fruits, vegetables and spices. The most famous and defined effect of salicylic acid is prostaglandin synthesis inhibition. Salicylic acid has antiinflammatory effects through suppression of transcription of genes for cyclooxygenase. Most of the pharmacological properties of salicylic acid can be contributed to the inhibition of prostaglandin synthesis. Also, it was discovered that salicylic acid has other in vivo cyclooxygenase-independent pathways. Since salicylic acid does not inhibit cyclooxygenase considerably, the anti-inflammatory effect is not a consequence of direct inhibition of cyclooxygenase activity. Because of its fundamental role, it was suggested that inhibition of nuclear factor kappa B by salicylic acid is one of the key anti-inflammatory mechanisms of action for salicylates. One of the most studied properties of salicylic acid is its antioxidative activity. Salicylic acid is a confirmed inhibitor of oxidative stress. Salicylic acid is capable of binding iron. This fact is significant for antioxidative effect of salicylic acid because iron has an important function in the course of lipid peroxidation. Sažetak Salicilna kiselina je fitohemikalija sa povoljnim efektima na ljudsko zdravlje. Salicilna kiselina je fenolna komponenta i prisutna je u različitim biljkama, gde ima važnu ulogu u zaštiti od patogenih agenasa. U prirodi se nalazi u voću, povrću i začinima. Najpoznatiji i najbolje proučen efekat salicilne kiseline je inhibicija sinteze prostanglandina. Salicilna kiselina ostvaruje anti-zapaljensko dejstvo preko supresije gena za ciklooksigenazu. Većina farmakoloških svojstava salicilne kiseline mogu se objasniti inhibicijom sinteze prostanglandina. Otkriveno je da salicilna kiselina pored ovog ima i druga in vivo dejstva. Pošto salicilna kiselina ne inhibira značajno ciklooksigenazu, anti-zapaljensko dejstvo nije posledica direktne inhibicije ovog enzima. Predloženo je da je inhibicija nuklearnog faktora kapa B od strane salicilata jedno od glavnih mehanizama anti-zapaljenskog dejstva salicilata. Jedno od najviše proučavanih svojstava salicilne kiseline je antioksidativna aktivnost. Salicilna kiselina je dokazani inhibitor oksidativnog stresa. Salicilna kiselina ima sposobnost vezivanja gvožđa. Ova činjenica je značajna za antioksidativno dejstvo salicilne kiseline zbog toga što gvožđe ima važnu ulogu u procesu lipidne peroksidacije.

Serum levels of nitric oxide and endothelin-1 in patients treated with continuous ambulatory peritoneal dialysis

Abstract End-stage renal disease (ESRD) and its treatment modules affect almost all organs and organ systems including vascular endothelium. It is well known that disturbance of vasoactive substances (nitric oxide – NO and endothelin-1 – ET-1) production appears in these patients. There is a small number of studies which investigated serum levels of NO and ET-1 in ESRD patients treated with continuous ambulatory peritoneal dialysis (CAPD). Therefore our study aimed to measure serum levels of NO and ET-1 in this population. This study included 23 ESRD patients (10 males and 13 females) treated with CAPD, mean age 55.8 ± 15.8 years. Mean duration of CAPD treatment in this group of patients was 3.4 ± 14.7 years. Besides this group of patients (CAPD), we included a second group which consisted of 30 healthy controls [14 males, 16 females, mean age 51.8 (±15.6) years]. Our results show significantly higher serum levels of NO in CAPD patients ( ± SD = 19.09 ± 6.9) in comparison to the control group ( ± SD = 9.5 ± 1.9) (p < 0.05). There was no significant difference in serum levels of ET-1 between CAPD patients ( ± SD = 7.3 ± 5.6) and the control group ( ± SD = 6.6 ± 4.2), (p > 0.05). From our results, we concluded that imbalance in production of vasoactive substances is present in CAPD patients. This imbalance can lead to disturbance in local blood flow control. These pathophysiological mechanisms can cause significant hemodynamic disturbance (hypertension) and atherosclerosis.