PROTECTIVE EFFECT OF QUERCETIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN RATS

The aim of this study was to investigate the possible effect of quercetin on cisplatin-induced nephrotoxicity in rats. Experiments were done on thirty-two Wistar rats divided into four groups of 8 animals each. The CIS group received a single dose of cisplatin (8 mg/kg) intraperitoneally, whereas the CISQ group received quercetin intraperitoneally at a dose of 50 mg/kg for 9 days and a single dose of cisplatin intraperitoneally (8 mg/kg) on the fifth day. Animals in the Q group received quercetin (50 mg/kg) and the C group received saline (1 mL/day), both given intraperitoneally for 9 days. Quantitative evaluation of structural and functional alterations in the kidneys were performed by histopathological and biochemical analyses. Histological sections of kidney in CIS group revealed mild degenerative changes of proximal tubules and focal apoptosis of tubulocites, while glomeruli had reduced lobular appearance. In CISQ group these changes were ameliorated and less visible. Analysis of biochemical parameters showed significantly higher urea and creatinine serum concentrations in CIS group in comparison with C group and CISQ group (p<0.001). The concentrations of potassium and sodium in the CIS group were lower, but not statistically significant in comparison to the C group. Kidney MDA levels were found to be significantly higher in CIS group than those in C group (p<0.001), whereas the values for CISQ group were significantly lower than MDA recorded for CIS group (p<0.001). The results suggest that quercetin has the nephroprotective action and reduces lipid peroxidation in cisplatin-treated rats.Key words: Cisplatin, quercetin, nephrotoxicity, rat

Gentamicin nephrotoxicity in animals: current knowledge and future perspectives

Due to high relative blood flow the kidney is prone to drug-induced damage. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug-induced nephrotoxicity. In recent years gentamicin nephrotoxicity is significantly reduced by shifting to once daily dosage as well as by eliminating known risk factors. Application of gentamicin is still related to serious side effects which are reported more often compared to other antibiotics. Because gentamicin is still heavily used and is highly efficient in treating infections, it is important to find mechanisms to reduce its nephrotoxicity. This aim can only be achieved through better understanding of kidney metabolism of gentamicin. This problem has been extensively researched in the last 20 years. The experimental results have provided evidence for almost complete understanding of mechanisms responsible for gentamicin nephrotoxicity. We now have well described morphological, biochemical and functional changes in kidney due to gentamicin application. During the years, this model has become so popular that now it is used as an experimental model for nephrotoxicity per se. This situation can mislead an ordinary reader of scientific literature that we know everything about it and there is nothing new to discover here. But quite opposite is true. The precise and complete mechanism of gentamicin nephrotoxicity is still point of speculation and an unfinished story. With emerge of new and versatile technics in biomedicine we have an opportunity to reexamine old beliefs and discover new facts. This review focuses on current knowledge in this area and gives some future perspectives

HYPOTENSIVE AND CARDIOINHIBOTORY EFFECTS OF THE AQUEOUS AND ETHANOL EXTRACTS OF CELERY (APIUM GRAVEOLENS, APIACEAE)

In this study we present the effects of aqueous and ethanol extracts of celery (Apium graveolens L., Apiaceae) investigated on the mean blood pressure of anaesthetized rabbits and contractility of isolated atria of the rats. In our experiments were used rabbits and Wistar albino rats. The effects of extracts (0.5-15 mg/kg) on blood pressure were recorded directly from the carotid artery. Rat isolated atria was mounted in 10 ml tissue bath. An equilibrium period of 30 min was given before the application of the extracts (0.02-0.75 mg/ml). In anesthetized rabbit, intravenous administration of aqueous extracts induced least hypotensive effects (14.35±2.94%), while the ethanol extract caused the greatest fall in the blood pressure (45.79±10.86%). Hypotensive effects of the extracts were partially blocked by atropine (0.3 mg/kg), an unselective muscarinic receptor antagonist. In isolated rat atria both aqueous and ethanolic extracts of celery, exhibit a negative chronotropic and an inotropic action. Aqueous extract decreased rate of contractions for 12.88±2.74% and amplitude for 8.73±0.89%. Ethanol extract inhibited rate of the atria contractions for 34.26±5.69%, and amplitude for 25.40±3.61%. Pretreatment of the atria with atropine (1μM) partially blocked inhibitory response of aqueous and ethanol extracts. Ethanol extract of celery exhibited significantly greater hypotensive and cardio-depressant activities then aqueous extract (p<0.05). These data suggest that the aqueous and ethanol extracts of celery caused the hypotensive, negative inotropic and chronotropic effects, which could partially be mediated possibly via stimulation of muscarinic receptors. Inhibitory effect of ethanol extract was significant comparing to aqueous extract of celery

PROTECTIVE EFFECT OF THE VERAPAMIL UPON THE TUBULAR EPITHELIUM DESQUAMATION IN THE GENTAMICIN NEPHRO-TOXICITY

The protective effect of the verapamil upon the tubular epithelium desquamation of the rats in the gentamicin nephip-toxicity is analyzed. In the animals that received the gentamicin the necrosis and the tubular epitelium desquamation developed while in the animals treated by verapamil and gentamicin the degenerative changes took place along with an easier desquamation of the tubular epithelium. The animals that obtained only the gentamicin had a statistically important increase of the urea and creatine along with"a kalium decrease with respect to the animals treated by verapamil and gentamicin. On the basis of the obtained results the authors assume that the verapamil has a protective effect upon the tubular epithelium desquamation in the gentamicin nephro-toxicity

CHANGE OF THE ENZYME SDH ACTIVITY IN THE LIVER AND OF THE BIOCHEMICAL PARAMETERS IN THE BLOOD OF THE RATS TREATED WITH GENTAMICIN

The change of the enzyme SDH activity in the liver as well as the change of the biochemical parameters (sGOT, sGPT and bilirubins) in the blood of the rats treated with gentamicin. In the experimental group of animals treated with gentamicin (100 mg/kg TT/24 h) for eight days it was found that the highest SDH activity was in the peri venular zone of the acinus (+++), that the enzyme's reduced activity was in the intermediary zone (+) and that the SDH activity in the per portal zone of the acinus was just in traces (+). In the control group of animals treated with the physiological solution (1 ml/kg TT/24 h), the enzyme SDH activity was the most prominent in the perivenular zone of the acinus (+++), while in the intermediary and the periportal zone the enzyme's activity was preserved but somewhat weaker (++). The results of the comparative study of enzymohistochemical and biochemical changes confirm the existence of an important correlation between the gentamicin application and the observed changes

DIFFERENT EFFECTS OF THE ATROPINE UPON THE PENDULOUS MOVEMENTS OF THE PROXIMAL AND OF THE DISTAL COLON OF THE RABBIT

The influence of the non-selective blocker of the muscarinic receptors, namely of the atropine (1,7 x10-10 - 5x10-7). upon thependulousmovements of the proximal and of the distal colon of the rabbit was studied. In the correct proportion to the concentration the atropine reduces the amplitude of both the proximal (r=0,98; P<0,001) and of the distal colon (r= 0,97; P < 0,001). On the basis of the ED50 values - that amount to 7,7 ± 0,03 x 10-7 M for the proximal colon and 3,5 ± 0,06 x 10-5 M for the distal colon, the atropine recluces for twenty times the amplitude of the pendulousmovements of the rabbit's distal colon. Likewise, it reduces for dozen times the frequency of the pendulous movements of the distal colon (ED50 = 5 ± 0,02 x 10-6M) with respect to the proximal one (ED50 = 4,7 ± 0,06 x I0-5M). The atropine does not change the tone of the proximal colon (average relaxation is 5,47 ± 2,32 %) while it induces the concentrically-dependent relaxation of the distal colon (maximal relaxation amounts to 38.03 + 8,34). The ED50 values for the atropine while affecting the distal colon tone is 1,7 ± 0,03 x 10-6M

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 lt 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. Copyrigh

Ventilator Function Improvement in Patients Undergoing Regular Hemodialysis: Relation to Sex Differences

Uremic lung is different entity then oedema present in cardiovascular diseases or in adult respiratory distress syndrome as well. This state is one of the possible complications in patients with chronic renal failure (CRF) receiving regular hemodialysis (HD). There are several studies suggesting that in these patients in 30-40% cases pulmonary hypertension was developed. It is known that patients with primary pulmonary hypertension have peripheral airway obstruction The data also showed that primary as well secondary pulmonary hypertension are more often developed in females; even real reason is still unknown. The aim of the study was to estimate the ventilator functionimprovement in patients with CRF receiving regular HD related to sex differences. The study population consisted in 39 patients with CRF, with no cardiac and pulmonary diseases. These patients were treated by regular hemodialysis using bicarbonate or acetate mode, respectively. They were divided into two groups according to the sex. Spirometry parameters before and after onset of hemodialysis were recorded. The results were analyzed using Student t-test and presented as mean +/-SD. All p values <0,05 were considered significant. The result showed that ventilatory function in male patients is significantly improved, especially VC and FEV1, whereas in female patientsimprovement had not statistical significance. It can be concluded that one of the possible reasons for slight improvement of ventilatorfunction in female patients is pulmonary hypertension

The Effect of Calcium Channel Blocker Verapamil on Gentamicin Nephrotoxicity in Rats

Aminoglycoside antibiotics are obligated nephrotoxins and inevitably cause renal failure during prolonged use. Experimental models of gentamicin-induced nephrotoxicity have shown histopathological, ultrastructural and functional alteration with blood urea nitrogen and serum creatinine increase leading to acute renal insufficiency (ARI). The aim of our study was to emphasize effects of verapamil, a calcium channel blocker, on gentamicin-induced ARI in rats. Experiments were done on 50 male Wistar rats (250-300 g) divided in three experimental groups. G-group animals (20 rats) were treated daily with gentamicin in dose of 100 mg/kg during 8 days. GV-group animals (20 rats) were treated daily with verapamil in dose of 3 mg/kg and the same dose of gentamicin as in G-group during 8 days. The control group (10 rats) received 1 ml/day saline intraperitoneally. Histological examinations were done using hematoxylin and eosin, periodic acid Schiff and methenamine silver staining methods. Morphometric parameters included measurement of 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 G-group rats’ glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear neutrophils infiltration, while coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In GV-group rats’ glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis. Morphometric analyses showed statistically significant differences between the G-group and control group of animals in glomerular size, mean optical density and average roundness (p<0,05). On the other hand, morphometric analyses between GV-group and control group animals did not show statistically significant differences in any of parameters measured. Blood urea and serum creatinine concentration in G-group were significantly elevated in comparison with GV-group (p<0,05) but sodium and potassium levels in G-group were decreased compared to GV-group without statistical significance. Our results show that verapamil modify some of morphological and functional kidney alterations induced by gentamicin

The Effect of Calcium Channel Blocker Verapamil on Gentamicin Nephrotoxicity in Rats

Aminoglycoside antibiotics are obligated nephrotoxins and inevitably cause renal failure during prolonged use. Experimental models of gentamicin-induced nephrotoxicity have shown histopathological, ultrastructural and functional alteration with blood urea nitrogen and serum creatinine increase leading to acute renal insufficiency (ARI). The aim of our study was to emphasize effects of verapamil, a calcium channel blocker, on gentamicin-induced ARI in rats. Experiments were done on 50 male Wistar rats (250-300 g) divided in three experimental groups. G-group animals (20 rats) were treated daily with gentamicin in dose of 100 mg/kg during 8 days. GV-group animals (20 rats) were treated daily with verapamil in dose of 3 mg/kg and the same dose of gentamicin as in G-group during 8 days. The control group (10 rats) received 1 ml/day saline intraperitoneally. Histological examinations were done using hematoxylin and eosin, periodic acid Schiff and methenamine silver staining methods. Morphometric parameters included measurement of 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 G-group rats’ glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear neutrophils infiltration, while coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In GV-group rats’ glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis. Morphometric analyses showed statistically significant differences between the G-group and control group of animals in glomerular size, mean optical density and average roundness (p<0,05). On the other hand, morphometric analyses between GV-group and control group animals did not show statistically significant differences in any of parameters measured. Blood urea and serum creatinine concentration in G-group were significantly elevated in comparison with GV-group (p<0,05) but sodium and potassium levels in G-group were decreased compared to GV-group without statistical significance. Our results show that verapamil modify some of morphological and functional kidney alterations induced by gentamicin