Protective effect of curcumin nanoparticles versus curcumin on gentamicin-induced nephrotoxicity in albino rats: histological and immunohistochemical study

Introduction: Acacia senegal gum is commonly known as Arabic gum or gum Arabic(GA) which obtained from the branches and stems of the trees as a dried gummy exudates. It is widely used in food and pharmaceutical industries as emulsifier and suspending agent. It has many pharmacologic effects including gastrointestinal effects such as increasing the short chain fatty acids and enhance water and electrolytes intestinal absorption but variable effects on lipid metabolism. In chronic renal failure patients, gum arabic reduces serum urea nitrogen. It is a potent superoxide scavenger so that it have a good protective activity against acetaminophen-induced hepatotoxicity and doxorubicin-induced cardiotoxicity in rats. The Aim of study: In the present study, we investigated the protective effect of Acacia senegal gum against gentamicin (GM)-induced nephrotoxicity in male albino rats. Materials and Method: The animals were divided into three groups A (Control), B (GM-only treated rats, 80mg/Kg, IM for 7days) and C (GA 10g/100ml water, orally for 4weeks prior to GM treatment). The nephrotoxicity was evaluated biochemically by determination level of serum Creatinine (Crea), Urea (Urea) and Uric acid (UA) level and histologically by microscopic examination the degree of proximal tubular damage. Results: The results showed significant increase in the level of Crea, Urea and UA in animals treated with GM only. In group (C), the level of Crea was high significant compared with the control but the level of Urea was significantly decreased compared with the control and the level of UA was significantly decreased compared with group B but higher than the control. Conclusion: These results suggest that Acacia senegal gum has some nephroprotective in rats, may be due to its antioxidant activities of GA.

This study evaluated the effects of methanolic leaf extract of Pterocarpus santalinoides (MLEPS) on the recovery from gentamicin-induced nephrotoxicity in albino rats. Fresh leaves of P. santalinoides were collected, dried, pulverized, and extracted by cold maceration technique using 80% methanol. Thirty male albino rats randomly assigned into six groups (A–F) of five rats each were used for the study. Nephrotoxicity was induced in groups A–E by intra-peritoneal administration of gentamicin (GM) once a day at 100 mg/kg for 10 days. Thereafter, the nephropathic (NP) rat groups (A–E) were used to assess the therapy with MLEPS. Group A was given drinking water (negative control). Groups B, C, and D were treated orally with MLEPS at 125, 250, and 500 mg/kg, respectively. Group E was treated orally with silymarin at 200 mg/kg (positive control). Group F was not treated with GM and MLEPS (normal control). Parameters measured relating to kidney function were serum creatinine and urea concentrations, urine protein level, and 24-h water consumption. All the parameters were significantly (p 0.05) to that of the group F (normal control) rats on days 5 and 10 PTWE, though it was not significantly (p > 0.05) different from the untreated control (group A). Urine protein levels of rats treated with 500 mg/kg MLEPS (group D) were lower and comparable to that of rats treated with silymarin (group E). Also, treatment with MLEPS at 250 and 500 mg/kg led to amelioration of renal tubular necrosis in the NP rats. It was concluded that treatment with MLEPS at 500 mg/kg significantly improved recovery time from GM-induced kidney damage in rats, based on the enhancement of creatinine and urea clearance from blood, reduction of protein loss in urine, and amelioration of histological lesions.

Gentamicin (GM) is an effective aminoglycoside antibiotic against life-threatening Gram-negative bacteria. However, a major complication of therapeutic doses of GM is nephrotoxicity, which is believed to be related to the generation of reactive oxygen species. The present study was therefore aimed to investigate the protective effect of eugenol, a phenolic antioxidant, on GM-induced nephrotoxicity in Sprague-Dawley rats. Intramuscular injection of rats with GM (80 mg/kg body weight/day) for six consecutive days induced marked acute renal failure, manifested by a sharp significant increase in serum urea and creatinine levels, along with a significant depletion of serum potassium level, compared to normal controls. GM-induced renal dysfunction was attributable to enhanced oxidative stress, as revealed by decreased superoxide dismutase and catalase activities, glutathione depletion and increased lipid peroxidation. Furthermore, kidney lactate dehydrogenase activity, as an indicator of hypoxia, was significantly increased by GM administration. Eugenol (100 mg/kg body weight, per os) administered four days before and six days concurrently with GM (80 mg/kg body weight, i.m.) restored normal renal functions and suppressed GM-induced oxidative stress and hypoxia. Light microscopical examination of the renal tissues of GM-treated animals demonstrated severe tubular necrosis at the cortex and increased cellular inflammatory processes. However, these alterations were considerably reduced with eugenol coadministration. In conclusion, eugenol ameliorates GM-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense.

<p style="text-align: justify;"><strong>Background:</strong> Nephrotoxicity is an emerging health issue in many countries due to exogenous or endogenous toxicants. Many drugs are responsible for causing renal damage including antibiotics such as aminoglycoside, cisplatin, etc. Meanwhile some herbs are traditionally used to treat kidney disorders due to their nephroprotective properties. One of them is Tukhme- soya (Seed of Anethum sowa) from family Umbelliferae. This study aims to evaluate the Tukhm-e-soya in gentamicin induced nephrotoxic kidney models in Albino rats. <strong>Methods: </strong>The rats were divided in to eight groups and each group was comprised of six rats. Group I- VIII were control, toxic, hydro-alcoholic, ethanolic, petroleum ether, chloroform, acetone, aqueous groups respectively. 1% carboxy methyl cellulose was used as control and gentamicin was used as toxicant. Duration of the study was 8 days. Serum creatinine (S.Cr), Blood Urea Nitrogen (BUN), histopathological studies of kidneys, and lipid peroxidation (LPO), were evaluated. Results were analyzed using one-way analysis of variance followed by Dunnett&rsquo;s post hoc test.<strong> Results:</strong> BUN, S.Cr and LPO levels were significantly increased in toxicant group when compared with control. Groups III - VIII showed significantly lower values close to control group in these parameters. Study revealed that it has a potent antioxidant activity which may be responsible for its nephroprotective actions. <strong>Conclusion:</strong> Therefore, it is concluded that all the extracts and fractions of Tukhme soya were effective in nephroprotection but acetone fraction, hydroalcoholic and chloroform fractions were more effective than other groups. <p style="text-align: justify;"><strong>Key words: </strong>Nephroprotective, Tukhm-e-soya, Gentamicin, Histopathology, Lipid peroxidation.

Floral extract of Tecoma stans: A potent inhibitor of gentamicin-induced nephrotoxicity in vivo

Aminoglycoside antibiotic, gentamicin, is widely used against gram-negative bacteria; however, its clinical use is limited due to its nephrotoxicity. Saffron extract has been previously used to decrease oxidative stress induced by ischemia-reperfusion. Here, we studied the effect of aqueous saffron extract on gentamicin toxicity. Twenty-eight male Wister rats were divided randomly into 4 equal groups and were injected with gentamicin (100 mg/kg I.M.), aqueous saffron extract (5 mg/kg I.P.), combination of thereof, and saline (1 ml I.M.). All treatments were done for ten consecutive days. Gentamicin-administered rats showed increase in serum urea and creatinine and urinary Gamma-glutamyltranspeptidase (GGT) together with acute tubular necrosis while saffron co-administered rats revealed lower concentration of urinary GGT and serum urea and creatinine and lower degree of necrosis. Rats treated with saffron did not show any change in biochemical indices compared to control rats but they showed severe congestion in their kidney cortex. Our study has shown the protective effect of saffron on gentamicin-induced nephrotoxicity in rats.

Aim: To evaluate the protective and therapeutic potentials of corn silk extract on gentamicin (CN)-induced nephrotoxicity in albino rats.&#x0D; Study Design: The rats were randomly selected and grouped as follows: Group 1 (NC): Were given only food and water. They served as negative control. Group 2 (PC): Were treated with 80 mg/kg/day of CN over a period of 7 days. They served as the positive control. Protective Treatment: Group 3a (CN+CSP 200 mg/kg): Concurrently treated with 200 mg/kg corn silk extract and 80 mg/kg/day of CN for 7 days. 200 mg/kg corn silk extract continued for 30 days. Group 3b (CN+CSP 400 mg/kg): Concurrently treated with 400 mg/kg corn silk extract and 80 mg/kg of CN for seven days. 400 mg/kg corn silk extract continued for 30 days. Therapeutic treatment: Group 4a (CN+CST 200 mg/kg): Induction of nephrotoxicity with 80 mg/kg/day of CN for seven days before the administration of 200 mg/kg of corn silk extract for 30 days. Group 4b (CN+CST 400 mg/kg): Induction of nephrotoxicity with 80 mg/kg/day of CN for 7 days before the administration of 400 mg/kg of corn silk extract for 30 days.&#x0D; Methodology: At the end of the treatment, the animals were allowed to fast for 18 hours and later anaesthetized using chloroform. Whole blood samples were collected via cardiac puncture and put into lithium heparin bottles. The samples were then spun at 3500 rpm for 5 minutes to obtain plasma. Kidney specimens harvested were fixed in 10% formol saline. Sections were prepared using histological techniques and stained using Haematoxylin and Eosin stain. Urea was analysed using Berthelot’s enzymatic colorimetric method, creatinine using Jaffe’s enzyme-kinetic method while the estimation of Na+, K+, and Cl- were performed using Ion Selective Electrode (ISE) analyzer.&#x0D; Results: Significantly lower (p&lt;0.05) values of creatinine and urea were seen in protective and therapeutic treatment groups when compared against positive control. Potassium indicated significantly lower values especially in the therapeutic groups when compared against negative control while chloride indicated significantly higher values in 400 mg/kg rats compared with positive control at p&lt;0.05. Histology of the protective treatment groups showed slightly distorted glomerular space, vacuolations, and dilated proximal and distal tubules. The positive control and the therapeutic treatment groups indicated severely damaged glomerulus, glomerular space, proximal and distal tubules as well as loss of parenchymal materials and presence of kupffer cell infiltration were seen but less severe in the therapeutic group compared to the positive control.&#x0D; Conclusion: The results obtained suggest protective and therapeutic potentials of corn silk extract on gentamicin-induced nephrotoxicity in albino rats. However, the therapeutic efficacy was progressively gradual and not be fast-effective as documented in most traditional or herbal literatures.

Background As a highly effective antibiotic, gentamicin is used in the treatment of serious and life-threatening gram-negative infections. L-arginine (2-amino-5-guanidino-pentanoic acid) has a protective role on renal failure that induced by gentamicin administration and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to determine the influence of gender on nephroprotective effects of L-arginine (Arg) and/or taurine (Tau) on gentamicin (G) induced nephrotoxicity. Methods Adult Sprague-Dawley albino rats of both sexes (150-200 g, 48 male and 48 female), were bred from the animal unit of National Nutrition Institute, Cairo, Egypt. Male rats were divided randomly into 8 groups (n=6 per group) and the following treatments were given: Group 1 (negative control group): saline (2 ml/Kg/day, i.p); Group 2 (positive control group): was injected with G (100 mg/kg b.wt./day, i.p); Group 3 injected with G and treated with Arg (1.6 gm/kg b.wt /day, p.o); Group 4 injected with G and treated with Tau (0.75 gm/kg b.wt/day,i.p) and Group 5 injected with G and treated with combination of Arg and Tau at the same previously mentioned doses. The tested amino acids and their combination were also administrated to healthy rats (three groups) for ten consecutive days. Female rats were divided at random into eight groups and treated in the same fashion as above. Results Gentamicin administration resulted in nephrotoxicity as evidenced by significant elevation in serum creatinine (122% and 127%) and blood urea nitrogen (BUN) (18.3% and 117%), significant reduction in creatinine clearance (30% and 46.9%), proteinuria (250% and 372%), sharply elevated levels of urinary alkaline phosphatase (ALP) (267% and 415%) and potassium (244% and 376%) and decreased level of serum ALP (10.2% and 31.9%) in males and females, respectively. Gentamicin did not affect serum potassium in both males and females and on serum sodium in males; however, it increased serum sodium in females by 27%. Also, gentamicin injection enhanced lipid peroxidation as indicated by the elevated levels of renal malondialdehyde (MDA) (46.7% and 22.8%) and nitric oxide (NO) (48% and 72%) and the depressed level of reduced glutathione (GSH) in kidney (55% and 45%) and whole blood (5.7% and 8.8%) in male and female rats, respectively, as compared with normal rats. Also, the activity of erythrocyte Cu, Zn superoxide dismutase (SOD) was reduced (10.1%) in males but not in females as compared with normal rats. Supplementation with Arg and/or Tau attenuated G induced nephrotoxicity in male and female rats. These nephroprotective effects were more pronounced in females. Conclusion The results of the present study indicate that female Sprague-Dawley rats are more sensitive to the nephrotoxic effects of G. Treatment with Arg and/or Tau exerted a nephroprotective impact, which is gender specific.

Background Caspase-3 plays an important role in apoptosis. In this study, we determined the protective effect of ginseng against gentamicine-induced nephrotoxicity in albino rats. The aim of this study was to investigate the protective effect of ginseng on the expression of caspase-3 in gentamicine-induced nephrotoxicity. Materials and methods A total of 40, adult, albino rats weighing 250±20 g were divided into four groups (10 rats each) and treated by intraperitoneal injection for 10 days with 1 ml of isotonic saline (group 1), gentamicine 100 mg/kg/day (group 2), gentamicine 100 mg/kg/day plus ginseng 100 mg/kg/day (group 3), and gentamicine 100 mg/kg/day for 10 days and then ginseng 100 mg/kg/day for another 10 days (group 4). After the last injection, blood urea and creatinine levels were calculated, and tissue samples were obtained for haematoxylin and eosin, Masson trichrome, periodic acid-Schiff (PAS), and caspase-3 staining. Results In group 2, body weight of rats decreased, serum urea and creatinine levels increased, and glomerular and tubular histological changes were observed, compared with the control group. When ginseng and gentamicine were given together (group 3) or when ginseng was given after gentamicine (group 4), body weight, serum urea and creatinine, and histological features showed improvement. Significant reactivity of caspase-3 in the distal renal tubules was observed in group 2 as compared with weak reactivity in group 3 and group 4. Conclusion Gentamicine has the ability to induce nephrotoxicity, mainly tubular, and ginseng may improve this nephrotoxicity.

Oxidative stress plays a central role in the mechanism of gentamicin-induced nephrotoxicity. The antioxidant properties of Cyperus esculentus (CE) have been reported. This study aimed to explore its potential in ameliorating symptoms of nephrotoxicity in a gentamicin-induced model. Tubers of CE were extracted with distilled water. Phytochemical analysis was done using standard protocols. Twenty-five male Wistar albino rats were divided into five groups of five animals each and treated for 8 days: Group I received normal saline, Group II (Gentamicin group)-gentamicin 80 mg/kg + distilled water, Group III-V were administered 80 mg/kg gentamicin +100, 200 and 400 mg/kg CE respectively 1 hour after gentamicin treatment. The rats were anesthetized and blood was collected via cardiac puncture for biochemical analysis. The gentamicin group showed significant increase in serum urea and creatinine levels compared to the control group. Cyperus esculentus resulted in a further elevation of these parameters in a dose-dependent manner. Furthermore, there was a significant increase in serum potassium and a significant decrease in bicarbonate at 400 mg/kg CE. Histological results further buttressed the biochemical findings. In conclusion, oral administration of Cyperus esculentus in gentamicin-induced nephrotoxicity resulted in a further elevation in serum levels of urea, creatinine, and potassium as well as a decrease in serum bicarbonate, and failed to protect against gentamicin-induced nephrotoxicity.

Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted.

To see the effects of Nigella sativaon acetylsalicylic acid-induced nephrotoxicity in albino rats. An experimental study. The Anatomy Department of University of Health Sciences, Lahore, from January 2014 to December 2015. Thirty-two female albino rats were divided into four groups. Group A(control) was given single dose of 10 mg/100 gm body weight of 1% methylcellulose, orally. Group B and C were treated with oral 1000 mg/kg acetylsalicylic acid as a single dose. Group D was given 250 mg/kg ethanolic extract of Nigella sativa(NSE) by oral gavage followed by single dose of 1000 mg/kg acetylsalicylic acid on 1st day of experiment; after that only NSE was continued till 7 days. Animals of groups A, C and D were sacrificed on day 8 and that of group B on day 2 of experiment. Cardiac puncture was performed to draw blood from each animal for renal function tests. Animals were evaluated for gross (Paired kidney weight, body weight, relative tissue body weight index) as well as for biochemical (Serum urea and creatinine) parameters. Gross as well as biochemical parameters were markedly impaired in group B, but statistically significant improvement was noticed in Nigella sativatreated group. There was no self recovery in group C. Ethanolic extract of Nigella sativahas a protective role against acetylsalicylic acid-induced nephrotoxicity in albino rats.

Background: Diabetes is a common cause of end-stage renal disease and nephropathy, which is characterized by abnormal renal function with reduction of glomerular filtration and rise in the level of serum urea and creatinine. Aims and Objectives: The aim of this study was to compare serum urea and creatinine levels in Type 1 and Type 2 diabetics and further correlate the serum creatinine and urea levels in both Type 1 and Type 2 diabetic subjects with duration of diabetes and glycosylated hemoglobin levels (HbA1c). Materials and Methods: Blood samples were collected and analyzed for serum urea and creatinine levels in diabetic subjects, both Type 1 and Type 2 attending diabetic clinic and non-diabetic subjects in a tertiary hospital. 72 male subjects in each group of age 35-55 years were selected for the study. Fasting, post-meal blood sugar levels, and HbA1c of all the subjects in the study were determined. Results were interpreted by one-way analysis of variance test. Association of serum urea and creatinine levels with HbA1c and duration of illness in all diabetic subjects was analyzed by applying Pearson’s correlation coefficient. Results: There was statistically significant increase in serum urea and creatinine levels in both Type 1 and Type 2 diabetic subjects compared to non-diabetic subjects. There was a correlation of levels of serum urea and creatinine with HbA1c levels and duration of diabetes in Type 1 diabetics but not with Type 2 diabetic study group. Conclusion: Serum urea and creatinine are simple and useful biomarkers which can serve as predictor tests for assessing kidney functions (nephropathy) in diabetic patients.

Objective: The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Design: Controlled study. Animals: Seven groups of male albino rats. Procedures: Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. Group 1: injected I.P with normal saline (control), Group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), Group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, Group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and Group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. Results: The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. Conclusion and clinical relevance: The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.

The most important side effect of gentamicin (GM) is nephrotoxicity. p-Coumaric acid (PCA) is a phenolic compound that scavenges free radicals, reduces fibrosis, and tissue damage. This study investigates the protective effect of PCA on tissue damage and kidney function in gentamicin-induced nephrotoxicity (GIN). Thirty-five rats were separated into five groups and each group contained seven animals: control group, ethanol group, GM group, PCA group, and GM + PCA group. At the end of the seven-day treatment, the rats were sacrificed after blood and kidney tissue samples were taken. While serum urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) levels increased significantly in the GM group compared to the control, they showed a significant decrease in the GM + PCA group compared to the GM. Serum tumor necrosis factor-α (TNF-α) and tissue malondialdehyde (MDA) levels were significantly increased in the GM group compared to the control. While the tissue total oxidant status (TOS) and oxidative stress index (OSI) values of the GM group were significantly higher than the control, they showed a significant decrease in the GM + PCA group compared to the GM. In the histopathological examination, significant tubular necrosis and tubulointerstitial inflammation were detected in the proximal tubules in the GM group compared to the control, while a significant decrease was observed in the severity of these findings in the GM + PCA group compared to the GM. This study shows that PCA has biochemical and histopathological ameliorating effects on GIN in the rat model.