Nenad Stojiljković

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.

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.

Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats.

AIMS One of the most popular beverages worldwide, green tea, was investigated for its potential protective effect in a rat model of gentamicin-induced nephrotoxicity by monitoring functional and morphological changes in kidneys. MAIN METHODS The study was conducted on four groups of rats: control group (C), treated with only gentamicin (GM), treated with only green tea (GT) and treated with both gentamicin and green tea (GT+GM). Kidney function, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Morphometric analysis was used to quantify these histopathological changes. KEY FINDINGS Gentamicin caused significant elevations in serum creatinine and urea and oxidative stress parameter (AOPP), while antioxidative enzyme catalase was significantly decreased. Histological sections of kidneys in GM group revealed necrosis of proximal tubules, vacuolation of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin histologically showed renoprotective effect. Histological results were confirmed and quantified by morphometric analysis. Also in this group we measured ameliorated parameters of renal functions and antioxidative defense. SIGNIFICANCE Regenerative potential of green tea after renal injury induced by gentamicin could be explained through the decrease of oxidative stress and lipid peroxidation. Green tea is a natural antioxidant, with many health promoting effects, widely available and in accordance to that affordable. Because of the established habits, people largely consume it as a beverage. It could be beneficial in the reduction of oxidative stress and changes caused by it primarily in renal tubules and interstitium.

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.

Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats.

Abstract Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic effects often characterized by both morphological and functional alterations of kidney leading to acute renal failure. The aim of this study was to examine the effect of dietary calcium supplementation on GM-induced nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats divided into three groups of 10 animals each. G-group received GM intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as control, received 1 mL/day of normal saline. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural and functional changes of kidney was performed by histopathological, morphometrical, and biochemical analyses. Compared with control, G-group of rats were found to have diffusely and unequally thickened glomerular basement membrane with neutrophil cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule cells with coagulation-type necrosis was observed. These GM-induced pathological lesions were significantly reduced in the rats of GCa-group. Morphometric analysis revealed statistically significant differences in the size of glomeruli (area, major and minor axes, perimeter), optical density, and roundness of glomeruli (p < 0.05) between G and GCa groups. Biochemical analysis showed significant elevation in blood urea and serum creatinine concentrations, whereas potassium concentration was lowered in G-group compared with the other groups (p < 0.01). It is concluded that oral supplementation of calcium during treatment with GM resulted in significant reduction of morphological and functional kidney alterations.

Specific alterations of physiological parameters in competitive race walkers.

Race walking is the technical and athletic expression of fast walking and it can be considered as a type of endurance performance. The purpose of this study was to examine whether 12 weeks of a specially designed training program results in the further training enhancement of endurance performance and the related physiological parameters in already well-trained race walkers competing at the national and international level. The investigation protocol consisted of determining the maximal oxygen uptake (VO2peak) and related gas exchange values using an automated cardiopulmonary exercise system and of determining blood lactate variables (aerobic threshold - LTAer and the maximal lactate steady state - MLSS) during walking with proper technique at 8, 10, 12 and 14 km·h-1 for 4 minutes without rest in between. Thereafter, the speed on the treadmill was increased by 0.5 km·h-1 every two minutes until exhaustion to determine VO2peak. After 12 weeks of a specially designed endurance training, statistically significant increases in VO2peak (61.8±8.5 mL·kg-1·min-1 pre vs. 66.9±9.5 mL·kg-1·min-1 post training; p<0.05) and blood lactate variables (VO2-LTAer and VO2-MLSS; p<0.05) were noted. The obtained results suggest that the applied training program can improve endurance and race performance in previously well trained race walkers.

Exercise training in overweight and obese children: Recreational football and high-intensity interval training provide similar benefits to physical fitness

This study compared the effects of recreational football and high‐intensity interval training (HIIT) on body composition, muscular fitness, and cardiorespiratory fitness in overweight and obese children. Forty‐two overweight/obese males aged 11‐13 years [body mass index (BMI) >20.5 kg/m2] were randomly assigned to a recreational football training group (n = 14; 157.9 ± 5.8 cm; 63.7 ± 12.6 kg), HIIT group (n = 14; 163.8 ± 9.4 cm; 71.5 ± 10.5 kg), or nontraining control group (n = 14; 162.7 ± 9.3 cm; 67.4 ± 16.1 kg). Physical fitness components were measured at baseline and after 12 weeks of training at the same time of the day and under similar conditions, including body composition, muscular fitness (lower‐body power, change‐of‐direction speed, and flexibility), and cardiovascular fitness (Yo‐Yo Intermittent Endurance test distance, resting heart rate, and blood pressure). Lean body mass (4.3%, ES = 0.40; 95% CI: −0.48, 1.29; P = .382) and muscle mass 4.4% (ES = 0.40; 95% CI: −0.48, 1.29; P = .378) very likely increased in the recreational football group, while possible improvements were observed in the HIIT group (lean body mass: 2.5%, ES = 0.22; 95% CI: −0.62, 1.06; P = .607, muscle mass: 2.8%, ES = 0.23; 95% CI: −0.61, 1.07; P = .594). Only trivial increases were observed in the control group for lean body mass (0.5%, ES = 0.05; 95% CI: −0.70, 0.79; P = .906) and muscle mass (1.1%, ES = 0.09; 95% CI: −0.65, 0.83; P = .814). Significant differences were found between the recreational football and control groups in post‐training body mass (P = .034) and body mass index (P = .017). Body fat very likely decreased in the recreational football group (−7.7%, ES = −0.41; 95% CI: −1.29, 0.48; P = .376) and possibly decreased in the HIIT group (−5.2%, ES = −0.22; 95% CI: −1.05, 0.62; P = .607), with a trivial reduction in the control group (−1.1%, ES = −0.04; 95% CI: −0.78, 0.70; P = .914). Very likely increases in lower‐body power were evident in the recreational football (17.0%, ES = 0.76; 95% CI: −0.15, 1.66; P = .107) and control groups (16.1%, ES = 0.55; 95% CI: −0.20, 1.31; P = .156), while small improvements were observed in the HIIT group (6.0%, ES = 0.24; 95% CI: −0.60, 1.08; P = .580, possible). Likely to most likely improvements in Yo‐Yo Intermittent Endurance test performance and change‐of‐direction speed were noted in the recreational football group (Yo‐Yo: 79.8%, ES = 1.09; 95% CI: 0.16, 2.03; P = .025, change‐of‐direction speed: −10.6%, ES = −1.05; 95% CI: −1.98, −0.12; P = .031) and the HIIT group (Yo‐Yo: 81.2%, ES = 1.03; 95% CI: 0.15, 1.92; P = .025, change‐of‐direction speed: −5.4%, ES = −0.91; 95% CI: −1.79, −0.04; P = .045). Diastolic blood pressure likely decreased in the recreational football (−8.6%, ES = −0.74; 95% CI: −1.64, 0.17; P = .116) and HIIT groups (−9.8%, ES = −0.57; 95% CI: −1.40, 0.30; P = .195), with a possible increase in the control group (1.2%, ES = 0.21; 95% CI: −0.53, 0.96; P = .068). Recreational football and HIIT elicited improvements in all muscular and cardiorespiratory fitness measures. In contrast, the control group, which performed only physical education classes, increased body mass, BMI, and fat mass. Therefore, additional activities such as recreational football or HIIT might counter the prevalence of overweight and obesity in children.