Gentamicin In Rats Research Articles

Renal protective effect of cardamom against nephrotoxicity induced by gentamicin in rats

This study was conducted to evaluate the renal protective effect of cardamom against experimentallyinducedgentamicin toxicity in rats. Forty adult male Westar albino rats were randomly grouped intofour groups (each of 10 rats). Rats in group (1) were orally administered saline (the vehicle) daily for 8consecutive days and severed as control group. Group 2: were given gentamicin (80 mg/kg. b.wt. i.p.)daily for 8 consecutive days. Group 3: were given gentamicin (80 mg/kg. b.wt. i.p.) daily for 8consecutive days, then cardamom extract (100 mg/kg. b.wt. p.o.) daily from 9th to 21th days. Group 4:were given gentamicin (80 mg/kg. b.wt. i.p.) daily for 8 consecutive days, then cardamom extract (200mg/kg. b.wt. p.o.) daily from 9th to 21th days. Gentamicin-treated rats showed significant renal damageas it increases creatinine, urea, glucose and total protein showed a significant decrease. While In groups(gentamicin + cardamom 100 mg/kg & gentamicin + cardamom 200 mg/kg), showed significantprotection to rats kidney from structural and functional changes associated with gentamicin. Gentamicinwhich induced nephrotoxicity can be prevented by co-administration with cardamom

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats

Gentamicin is a member of aminoglycosides, which has represented highly effective antimicrobial agents especially in Gram-negative infections despite their toxic effects in the kidney. Rapid diagnosis is vital to preserve renal function and to slow down renal injury. Owing to the poor sensitivity and specificity of serum creatinine (SCr) and blood urea nitrogen (BUN), new biomarkers for earlier and more accurate detection are needed. The aim of our study was to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful biomarkers in the assessment of gentamicin-induced nephrotoxicity in rats. In this study, the two biomarkers of renal toxicity were assessed via ELISA, quantitative real-time PCR, and immunohistochemistry in rats treated with gentamicin for up to 7days. Repeated administration of gentamicin to male SD rats for 1, 3, or 7days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. Changes in gene and protein expressions were found to correlate with the progressive histopathological alterations and preceded effects on traditional clinical parameters indicative of impaired kidney function. Both of the biomarkers are supported to be used as sensitive indicators of acute kidney injury caused by gentamicin.

Garlic supplemented diet attenuates gentamicin nephrotoxicity ın rats.

To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. Twenty four healthy male Wistar rats, weighing between 220 - 260 grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples.

English

Ginger rhizome (Zingiber officinale R., family: Zingiberaceae) is used medicinally and as a culinary spice. Gentamicin is synthetic antibacterial agent antibiotic with a very broad spectrum against microbial pathogens, especially the gram-negative. The aim of this study was to investigate the recovery effect of ginger on testis after treatment with gentamicin in rats. The forty male Wistar rats were selected and randomly divided into control (n = 10) and experimental (n = 30) groups. The experimental groups were split into three groups. First group, second experimental group which received 50 mg/kg (IP) gentamicin and one group treated with 100 mg/kg/rat/day of ginger rhizome via gavages daily for 30 days, respectively. However, the control group just received normal saline (IP). On the thirteeth day, after taking biopsy from testis of each group, tissue preparation was performed and analyzed for apoptosis. There was a significant increase in apoptosis in gentamicin groups when compared with other groups (P < 0.05). Gentamicin antibiotic have negative effect on sperm parameters and testis histology in rats. However, these side effects are less seen in the gentamicin group that received 100 mg/kg/rat of ginger. Therefore, it is recommended that usage of ginger with gentamicin has fewer side effects on male fertility. Key words: Apoptosis, gentamicin, Zingiber officinale, testis tissue.

Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats

This study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced testicular toxicity and oxidative damage in rats. GM (100mg kg(-1) ) was injected intraperitoneally (i.p.) to rats for 6days. MT (15mg kg(-1) ) was administered i.p. to rats for 6days at 1hr after the GM treatment. GM caused a decrease in prostate and seminal vesicle weights, sperm count and sperm motility. Histopathological examination showed various morphological alterations in the testis, characterised by degeneration of spermatogonia/spermatocytes, decrease in the number of early spermatogenic cells and vacuolisation. In addition, an increased malondialdehyde concentration and decreased glutathione content and glutathione reductase, catalase and glutathione-S-transferase activities were found in the testis. In contrast, MT treatment significantly attenuated the testicular toxicity of GM, including decreased reproductive organ weights, sperm count, and sperm motility and increased histopathological alterations. MT also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the level of the antioxidant glutathione and the activities of antioxidant enzymes in the testis. These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity.

Comparison of inhalation toxicity studies of gentamicin in rats and dogs

Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245 mg/kg for rats (deposited doses 6, 17 and 34 mg/kg) over 30, 90 and 180 min, respectively. Since dogs do not tolerate exposures as long as rats, inhaled lung doses were limited to 7, 14 and 41 mg/kg (deposited doses of 1, 3 and 8 mg/kg) over 15, 30 and 60 min. Comparable doses were achieved at the low dose for rats and high dose for dogs. Serum AUCs (14 ± 2 µg/mL*h (mean ± SD) at 6 mg/kg in rats and 11 ± 7 µg/mL*h at 8 mg/kg in dogs) showed comparable exposure between the two, implying similar absorbed doses and confirming similar deposited lung doses. Rat exposures resulted in dose-related lung pathology (including low dose) manifested as upper respiratory tract irritant reactions with alveolar histiocytosis, inflammation, airway epithelial metaplasia and lymphomegaly in lung tissue. This was associated with high lung tissue gentamicin levels 24 h post-dose on Day 14 (375 ± 33 µg/g at deposited dose of 6 mg/kg). Dose-related kidney tubular necrosis (a well-known toxicity of parenteral gentamicin) was observed, but no test-article related effects on lung histopathology in dogs (even at highest deposited dose of 8 mg/kg) and low levels of lung tissue gentamicin (42 ± 11 µg/g) 24 h post-dose on Day 14.

Red ginseng protects against gentamicin-induced balance dysfunction and hearing loss in rats through antiapoptotic functions of ginsenoside Rb1

The authors evaluated the protective effects of Korean red ginseng (KRG) against gentamicin (GM)-induced unilateral vestibular and hearing dysfunction and investigated its effective mechanism using in vitro cell cultures. Vestibular function was comprehensively evaluated by a scoring system that ranged from 0 (normal) to 3 (worst) points, using head tilt, tail hanging, and swimming tests. The GM group showed significantly more deteriorated vestibular function (0 point--5 rats, 1 point--1 rat, 2 points--3 rats, and 3 points--3 rats) than the KRG+GM group (0 point--9 rats and 1 point--1 rat) (p<0.01). The hearing thresholds were better in the KRG+GM group than in the GM group (p<0.05). Quantitative analysis of hair cell damage in the scanning electron microscopy was closely related with vestibular and hearing functional results. In vitro study showed that ginsenoside Rb1 (gRb1) attenuated reactive oxygen species production, suppressed JNK activation, up-regulated Bcl-xL and down-regulated Bax, cytochrome c, caspase 3, and cleaved poly (ADP-ribose) polymerase in GM-treated VOT-E36 cells. These findings suggest that KRG including gRb1 component protects against vestibular/hearing dysfunction by inhibiting apoptotic pathways when ototoxicity is induced by unilateral intratympanic injection with GM in rats.

Histone deacetylase inhibitor, sodium butyrate, attenuates gentamicin-induced nephrotoxicity by increasing prohibitin protein expression in rats

The major purpose in our study was to investigate the effects of sodium butyrate (NaBu) on nephrotoxicity induced by gentamicin in rats and determine further whether the protective effect is mediated by modulation of prohibitin protein expression. Gentamicin was injected intraperitoneally (100mg/kg body weight) once daily for 8 days to induce nephrotoxicity. The effect of acute and chronic treatment of sodium butyrate on nephrotoxicity induced by gentamicin was assessed. Various doses of sodium butyrate (50, 100, 200mg/kg, i.p.) was administered 30min prior to the daily gentamicin injection. Histological analysis was used to evaluate the lesions in kidney after gentamicin administration. Expression of prohibitin was evaluated with immunohistochemical and western blot analysis. The present study demonstrated that gentamicin treatment for 8 consecutive days significantly increased in the levels of blood urea nitrogen, creatinine, kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) which indicated nephrotoxicity induced by gentamicin. In addition, chronic treatment with NaBu significantly attenuated gentamicin-induced nephrotoxicity by increasing activities of superoxide dismutase, catalase and reduced glutathione. Immunohistochemical studies in gentamicin-induced rats also demonstrated an increase in the levels of inducible prohibitin after treatment with sodium butyrate. Our results indicated that sodium butyrate, a histone deacetylase inhibitor, decreased gentamicin-induced nephrotoxicity by enhancing renal antioxidant enzymes activity and the expression of prohibitin protein.

Inhibition of cystathionine gamma-lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity

Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong anti-inflammatory, anti-apoptotic and cytoprotective properties. In several models of inflammatory disease however, tissue damage has been associated with increased activity of cystathionine gamma-lyase, biosynthesis of hydrogen sulphide and activation of leukocytes. The aim of this study was to determine effects of inhibiting hydrogen sulphide biosynthesis by DL-propargyl glycine (an irreversible inhibitor of cystathionine gamma-lyase) on inflammation, necrosis and renal function, following treatment with gentamicin in rats. Adult female Sprague–Dawley rats were divided into six groups and treated with; physiological saline, sodium hydrosulphide, DL-propargyl glycine, gentamicin, a combination of gentamicin and sodium hydrosulphide, or gentamicin and DL-propargyl glycine respectively. Gentamicin-induced histopathological changes including inflammatory cell infiltration and tubular necrosis were attenuated by co-administering gentamicin with DL-propargyl glycine (P<0.05 compared to saline controls and P<0.05 compared to gentamicin only). Similarly, DL-propargyl glycine caused a significant reduction (P<0.05) in lipid peroxidation, production of superoxide and the activation of tumour necrosis factor-alpha in gentamicin-treated animals. These data show that protective effects of DL-propargyl glycine might be related at least in part, to the reduced inflammatory responses observed in animals treated with both gentamicin and DL-propargyl glycine. Thus, enzyme systems involved in hydrogen sulphide biosynthesis may offer a viable therapeutic target in alleviating the nephrotoxic effects of gentamicin.

Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15 mg/kg/day), (3) GM (100 mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury was mediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.

Antioxidant protecting effects of vitamin B6 at reducing hemodynamic toxicity of gentamicin in rat model of nephrotoxicity

Routine therapeutic use of gentamicin in patients with preexisting renal failure may confront us with the toxic effects of aminoglycosides in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant protecting effects of vitamin B6 in the kidney, with a view on vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of gentamicin. Hence, 50 male Sprague–Dawley rats were randomly assigned in five groups to receive a corresponding dose of either normal saline, vitamin B6 (100 mg/kg/bw; i.m.) or gentamicin alone (80 mg/kg/bw; i.m.), or in combination with vitamin B6 at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of nephrotoxicity. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in local and systemic oxidative stress and a decrease in glomerular functions as result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of the experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B6 at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to low-dose rats and controls. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin B6 consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin B6 prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.

Dose-related protecting effects of vitamin C in gentamicin-induced rat nephrotoxicity: a histopathologic and biochemical study

Gentamicin remains the mainstay in treatment of gram-negative infections, despite its potential ototoxicity and nephrotoxicity. In this study, we investigated dose-related protecting effects of vitamin C against gentamicin-induced rat nephrotoxicity. Hence, 50 male albino Wistar rats were randomly divided into five equal groups to receive a corresponding dose of either normal saline as control, vitamin C (200 mg/kg/bw, i.m.) or gentamicin alone (80 mg/kg/bw, i.m.) or in combination with vitamin C at low dose (200 mg/kg/bw, i.m.; LVG) and high dose (600 mg/kg/bw, i.m.) for 9 days. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in oxidative stress in renal tissues and plasma and a concomitant decrease in the creatinine clearance and renal blood flow as result of early hemodynamic toxicity. Histopathological examinations revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies showed protecting effects of supplemented vitamin C at a high dose, including slowdown in the urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and the ATPase activity up to 50% when compared to controls and low-dose rats (LVG). In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin C consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin C prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.

Garlic-Supplemented Diet Attenuates Gentamicin-Induced Ototoxicity: An Experimental Study

Gentamicin sulfate is a potent aminoglycoside antibiotic associated with serious side effects, including ototoxicity. Garlic, with its intrinsic antioxidant activity, may prove beneficial in prevention of ototoxicity. In this study, we investigated the effect of a 4% garlic-supplemented diet on the ototoxicity induced by gentamicin in rats by using brain stem evoked response audiometry. Eighteen male Wistar rats with an intact Preyer's reflex and an initial weight of 220 to 260 g were randomly assigned to a group with gentamicin injection and garlic supplementation, a group with gentamicin injection without garlic supplementation, or a control group (6 rats each group). Gentamicin was given by intraperitoneal injection at 120 mg/kg body weight once daily for 16 days. The garlic-supplemented diet was prepared by adding pulverized whole garlic cloves to standard chow in a 4% proportion. After 21 days, hearing thresholds were evaluated by use of brain stem evoked response audiometry at 10 kHz. The mean (+/- SD) amplitudes of the auditory thresholds (sensation level) measured by use of brain stem evoked response audiometry for the group with garlic supplementation, the group without garlic, and the control group were 43.3 +/- 8.16, 78.0 +/- 4.47, and 16.7 +/- 5.16 dB sensation level, respectively. The differences were statistically significant (p < 0.05). A garlic-supplemented diet seems to attenuate aminoglycoside-induced hearing loss.

Blood chemical changes and renal histological alterations induced by gentamicin in rats

Gentamicin is an effective widely used antibiotic, but the risk of nephrotoxicity and oxidative damage limit its long-term use. Hence, the current study aims to elucidate such hazardous effects. To achieve the study aim male Wistar albino rats ( Rattus norvegicus) were exposed to gentamicin to investigate the resultant blood chemical changes and renal histological alterations. In comparison with control rats, gentamicin produced outstanding tubular, glomerular and interstitial alterations that included degeneration, necrosis, cytolysis and cortical tubular desquamation together with mesangial hypercellularity, endothelial cell proliferation and blood capillary congestion. Compared with control animals significant blood chemical changes ( P < 0.05) including free radicals, ALT, AST, ALP, serum creatinine and serum urea were recorded in gentamicin-injected animals. The findings revealed that exposure to gentamicin can induce significant histological alterations in the kidney as well as remarkable blood chemical changes that might indicate marked renal failure.

Nephrotoxicity and Oxidative Stress of Single Large Dose or Two Divided Doses of Gentamicin in Rats

Gentamicin (GS) is a potent antimicrobial exhibiting concentration dependent bacterial killing. A high dose ofgentamicin (10 mg kg(-1)) is required to reach sufficient concentrations in specific fluids as cerebrospinal fluid and to be effective on antibiotics resistant bacteria as well as treatment of acute and dangerous illness. Using a rat model, the renal toxicity and oxidative stress of administering gentamicin (10 mg kg(-1) daily for 7 days) either in a single dose or divided into 2 doses was investigated. The safety of dose regimens was assessed through oxidant-antioxidant parameters as well as renal function tests. Typical renal damage and high oxidative stress were evident in the control group receiving 100 mg kg(-1) gentamicin daily for 7 days. This was verified by high serum urea, uric acid, creatinine as well as increase in the levels of oxidative stress biomarkers as malondialdehyde, NO, total antioxidant capacity and decrease in reduced glutathione level. At any of the used regimen, 10 mg kg(-1) gentamicin did not provide high compromise for renal functions nor significantly increased the oxidative stress and tissue damage. Based on microscopic lesions scores and biochemical analysis, there were no significant differences between single or two divided dosages of gentamicin at dose rate of 10 mg kg(-1) day(-1). Further studies are required for applications in other animals of human subjects.

Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure

Rationale: Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. This study investigates whether green tea extract (GTE), an antioxidant, could ameliorate the nephrotoxic effect of GM in uninephrectomized rats. Objectives: The right kidneys of 40 rats were surgically removed and 1 week later the animals were divided into four groups (n = 10). Group 1 served as control, Group 2 as GTE group, Group 3 as GM group, and Group 4 as GM+GTE group. Kidney function, inflammatory cytokine TNF-α, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Main findings: Injecting uninephrectomized rats with GM induced renal dysfunction as shown by significant elevations in serum creatinine and urea. Serum TNF-α and oxidative stress parameters (superoxide anion and lipid peroxides) were also significantly increased. On the contrary, antioxidative parameters [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)] were significantly decreased. Histopathological examination of renal tissue illustrated features of degeneration, marked cellular infiltration, tubular dilatation, and varying degrees of necrosis. GTE given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and TNF-α were almost normalized in the GM+GTE group. The oxidative stress parameters were significantly decreased and the antioxidative parameters were significantly increased. Conclusion: GTE ameliorates GM-induced nephrotoxicity and oxidative damage by improving antioxidant defense and tissue integrity. Further human studies are necessary to demonstrate the antioxidant effects of GTE on renal diseases. Nevertheless, green tea (GT) may offer an inexpensive, nontoxic, and effective intervention strategy in subjects with a risk for GM-induced nephrotoxicity.

PROTECTIVE EFFECT OF DAILY SESAME OIL SUPPLEMENT ON GENTAMICIN-INDUCED RENAL INJURY IN RATS

Gentamicin, an aminoglycoside antibiotic, is widely used in the treatment of Gram-negative infections; however, dose-limiting nephrotoxicity restricts its optimal use. We investigated the effect of a daily sesame oil supplement on oxidative-stress-associated renal injury induced by a single daily dose of gentamicin in rats. Renal injury was induced by a single subcutaneous daily dose of gentamicin (100 mg kg(-1) d(-1) for 7 days), and then the effects of oral sesame oil (0.25, 0.5, and 1 mL kg(-1) d(-1) for 7 days) on renal injury, oxidative stress, hydroxyl radical, superoxide anion, and NO were assessed after treatment. Sesame oil inhibited gentamicin-induced renal injury, lipid peroxidation, hydroxyl radical, and superoxide anion, as well as NO production. In addition, sesame oil inhibited xanthine oxidase activity and inducible NOS expression in gentamicin-challenged rats. We hypothesize that a daily sesame oil supplement attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

Pentoxifylline Ameliorates Glomerular Basement Membrane Ultrastructural Changes Caused by Gentamicin Administration in Rats

Gentamicin is commonly used for the treatment of severe gram negative bacterial infections but inevitably cause renal failure during prolonged use. The aim of our study was to emphasize protective effects of pentoxifylline on glomerular basement membrane (GBM) alterations induced by gentamicin in rats. Experiments were done on 40 male Wistar rats divided in three experimental groups. GM-group was treated daily with gentamicin in dose of 100 mg/kg during 8 days. PTX-group was treated daily with pentoxifylline in dose of 45 mg/kg and the same dose of gentamicin as in GM-group during 8 days. The control group received 1 ml/day saline intraperitoneally. Morphometric parameter measured during the analysis was glomerular basement membrane thickness. In GM-group of animals glomeruli were enlarged and GMB was diffusely and unequally thickened with neutrophil cells infiltration. In proximal tubules epithelial cells, vacuolization of cytoplasm with coagulation-type necrosis were observed. In PTX-group of animals glomeruli were somewhat enlarged and GBM was thickened only in some segments. Coagulation-type necrosis was not found. Blood urea and serum creatinine concentration in GM-group were significantly elevated in comparison with PTX-group while potassium level was decreased. Our results suggest that PTX has protective effects on GBM and proximal tubules in GM-treated rats.

Selective nuclear factor κ‐B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin

To investigate the effect of selective nuclear factor kappa-B (NFkappa-B) inhibitors, pyrolidium dithiocarbamate (PD) and sulfasalazine (SZ) on renal tubular necrosis and inducible nitric oxide synthase (iNOS) and NFkappa-B expression induced by gentamicin in rats. In all, 48 adult male Sprague-Dawley rats were divided into six equal groups; group 1, control; group 2, injected with gentamicin for 10 days (100 mg/kg/day, intraperitoneal, i.p.); group 3, injected with gentamicin plus PD (100 mg/kg/day, i.p.); group 4, injected with gentamicin plus SZ (75 mg/kg/day, i.p.); group 5, injected with gentamicin plus distilled water (vehicle for PD); and group 6, injected with gentamicin plus ammonium hydroxide (75 mg/day, 1 m, vehicle for SZ) for 10 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. A small sample was fixed in formaldehyde solution for histological and immunohistochemical examination. Blood samples were also taken to assess the serum levels of urea, creatinine, Na(+), K(+) and gamma-glutamyl transpeptidase (GT). Crude extracts of the cortex were used to determine reduced glutathione (GSH-Px), NO and malondialdehyde (MDA). Immunohistochemically, iNOS and the active subunit of NFkappaB, P65, were evaluated using mouse monoclonal antibodies. On haematoxylin and eosin staining, compared with the controls rats, gentamicin caused widespread tubular necrosis (grade 3 and 4) but in group 3 and 4 there was a marked reduction in the extent of tubular damage. Immunohistochemically there was more marked staining for iNOS and P65 expression in rats given gentamicin than in the control and group 3 and 4 (P < 0.001). In groups 3 and 4 iNOS and P65 expression were significantly less than in rats given only gentamicin. There was no significant difference in serum levels of Na(+), K(+), blood urea nitrogen and creatinine. Compared with control rats, gentamicin caused hyperproteinuria, a marked increase in levels of serum gamma-GT, MDA and NO, and a decrease in GSH-Px (P < 0.001). These results indicate that gentamicin induces iNOS expression through activation of NFkappa-B (P65). It is possible to prevent gentamicin-induced nephrotoxicity using selective NFkappa-B inhibitors.