scholarly journals Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney

2016 ◽  
Vol 94 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Saeed Mehrzadi ◽  
Seyed Kamran Kamrava ◽  
Banafshe Dormanesh ◽  
Manijeh Motevalian ◽  
Azam Hosseinzadeh ◽  
...  

The risk of serious side-effects such as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in 5 groups, each containing 6 rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN, and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidney weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD, and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidney weight, renal ROS, and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.

2016 ◽  
Vol 21 (4) ◽  
pp. NP49-NP55 ◽  
Author(s):  
Habib Ghaznavi ◽  
Saeed Mehrzadi ◽  
Banafshe Dormanesh ◽  
Seyyed Mohammad Taghi Hosseini Tabatabaei ◽  
Habib Vahedi ◽  
...  

This study compared the possible protective effects of silymarin and melatonin against gentamicin (GEN)-induced nephrotoxicity in rats. Rats were allocated to 6 groups: Group I, control group; Groups II and III, administered with silymarin or melatonin; Group IV, injected with GEN; and Groups V and VI, administered with silymarin or melatonin, and then injected with GEN. Compared with the rats in the control group, all rats injected with GEN significantly presented elevated levels of serum creatinine and urea that was accompanied by an increase in relative kidney weight, increase in renal reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and reduction in renal glutathione (GSH) level and superoxide dismutase (SOD) activity. Silymarin and melatonin pretreatment significantly lowered the elevated serum urea and creatinine concentration, kidney weight, and renal ROS and MDA levels. In addition, silymarin and melatonin significantly enhanced renal GSH level and SOD activity. This study indicates that silymarin and melatonin can attenuate renal injury in rats treated with GEN possibly by reducing the ROS level.


1985 ◽  
Vol 107 (4) ◽  
pp. 562-564 ◽  
Author(s):  
Farahnak K. Assadi ◽  
Eunice G. John ◽  
Linda Fornell ◽  
Ira M. Rosenthal

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kamleshwar Shukla ◽  
Prince Raj ◽  
Arun Kumar ◽  
Mukesh Kumar ◽  
Gaurav Kaithwas

The present study was undertaken to elucidate the effect of pantoprazole and aprepitant on experimental esophagitis in albino rats. Groups of rats, fasted overnight, received normal saline (3 mL/kg, sham control) or toxic control (3 mL/kg) or pantoprazole (30 mg/kg) or aprepitant (10 mg/kg), or their combinations and were subjected to pylorus and forestomach ligation. Animals were sacrificed after 8 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index, and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with pantoprazole and aprepitant significantly inhibited the gastric secretion, total acidity, and esophagitis index. The treatment also helped to restore the altered levels oxidative stress parameters to normal.


2018 ◽  
Vol 25 (07) ◽  
pp. 1117-1123
Author(s):  
Faiza Irshad ◽  
Rabia Sajjad Toor ◽  
Madiha Hussain

Background: Zingiber Officinale Roscoe (Zingiberaceae family) is knownas Ginger. It is famous for its antioxidant properties. Objectives: To evaluate the effects ofGinger aqueous extract on the serum creatinine and paired kidney weight in Alloxan induceddiabetic nephropathy of albino rats. Study Design: Experimental study. Period: 06 months01-01-2013 to 30 June 2013. Setting: Anatomy Department, Sheikh Zayed, PGMI Lahore.Materials and Methods: Diabetes mellitus was induced with Alloxan intraperitoneally (150 mg/kg body weight) in Experimental groups B & C. Then the rats of experimental group C received200mg/kg body weight of ginger aqueous extract by gavage daily for five weeks starting from8th day after Alloxan injection. Results: Serum creatinine levels increased more in experimentalgroup B as compared to experimental group C. Group wise comparison of creatinine levelrevealed that the difference among control (A group) and experimental (B & C Groups) wassignificant having p-value <0.001. We observed that Paired kidney weight in experimentalgroup B increased as compared to control group A. Less increase in the paired kidney weightwas observed in experimental group C as compared to experimental group B. The differenceof mean paired kidney weight among three groups was significant having p-value <0.001.Conclusion: The results of the present study indicated that the co-treatment of Ginger aqueousextract prevented alloxan induced diabetic nephropathy in albino rats. The aqueous extract ofGinger showed amazing results on paired kidney weight.


2019 ◽  
Vol 20 (2) ◽  
Author(s):  
Sawsan El-Sheikh ◽  
Naglaa Eleiwa ◽  
Heba Nazim

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.


2015 ◽  
Vol 35 (3) ◽  
pp. 276-281 ◽  
Author(s):  
H Elbe ◽  
Z Dogan ◽  
E Taslidere ◽  
A Cetin ◽  
Y Turkoz

Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg−1 day−1 gavage for 21 days), ciprofloxacin (20 mg kg−1 twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman’s space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.


2014 ◽  
Vol 34 (5) ◽  
pp. 487-496 ◽  
Author(s):  
M Buyuklu ◽  
FM Kandemir ◽  
M Ozkaraca ◽  
T Set ◽  
EM Bakirci ◽  
...  

Currently, the number of imaging and interventional procedures that use contrast agents (CAs) is gradually increasing. Contrast-induced nephropathy (CIN) is the most important CA-related complication. Oxidative stress plays a significant role in its pathophysiology. Lycopene (LPN) is a natural substance with strong antioxidant capacity. The present study aimed to investigate the potential preventive effects of LPN against CIN. In total, 28 male Wistar albino rats were divided into 4 groups with 7 rats in each group; the groups include normal control group, LPN only group at a dose of 4 mg/kg/day for 10 days, CIN group by administering 10 mg/kg furosemide IM + 10 mg/kg indomethacin IP + 10 ml/kg iomeprol IV following 24-h dehydration, and CIN + LPN group. There were statistically significant increase in urea, creatinine, and malondialdehyde levels ( p < 0.001, for all) but a significant decrease in glutathione, superoxide dismutase, catalase, and glutathione peroxidase levels ( p < 0.001, for all) in the CIN group compared with the control group. On histological examination, a significant increase of infiltrated inflammatory cells and necrotic degenerative changes were observed in the CIN group and the immunohistochemical examination revealed a significant increase in inflammation (inducible nitric oxide synthase), autophagy (LC3/B), and apoptosis (cleaved caspase 3) in the CIN group compared with the control group ( p < 0.05, for all). Significant improvements in these unfavorable parameters were observed with CIN + LPN group compared with the CIN only group. In conclusion, the favorable effects of LPN as an anti-inflammatory, antiautophagic, and antiapoptotic agent in an experimental model of CIN have been demonstrated.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.


1999 ◽  
Vol 18 (12) ◽  
pp. 713-717 ◽  
Author(s):  
J-G Zhang ◽  
M Viale ◽  
M Esposito ◽  
W E Lindup

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S252-S252
Author(s):  
Justin Patrick Markelwith ◽  
Nikunj M Vyas ◽  
Mark Condoluci ◽  
Sungwook Kim

Abstract Background Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain some of the most difficult to treat due to extremely high rates of resistance. The purpose of this study was to compare the efficacy of dual vs. triple targeted antibiotic regimens for CRAB infections. Methods This was an IRB approved retrospective cohort study performed at a 607-bed community health system between January 2016 and December 2018. Patients were included in the analysis if they were ≥18 years old and received antibiotics for CRAB for ≥72 hours. Patients were excluded if they were pregnant and had CRAB isolated solely from the urine. The primary endpoints of the study were differences in all-cause in-hospital mortality (ACIM) and clinical cure (CC) rates for patients treated with dual vs. triple antibiotic therapy. The secondary endpoint result focused on the difference in length of stay (LOS) between treatment groups. A sub-group analysis was performed for patients treated with tigecycline vs. minocycline combination therapy to determine differences ACIM and CC, and LOS. A multi-logistic regression analysis (MLRA) was performed to determine patient factors that were associated with ACIM and CC. Results A total of 32 patients were included in the primary analysis. No difference was seen in ACIM between dual vs. triple antibiotic groups (9.5% vs. 18.2%, P = 0.59). CC (63.6% vs. 57.1%, P = 1.0) and LOS (12 vs. 11 days, P = 1.0) was similar amongst patients treated with dual vs. triple antibiotic group. No differences were seen in ACIM (15.4% vs. 16.7% P = 1.0), CC (83.3% vs. 69.2%, P = 1.0) and LOS (15 vs. 14 days, P = 1.0) between tigecycline and minocycline combination therapy groups. The MLRA revealed a positive association with increased serum creatinine and ACIM (OR 3.29, 95% CI 1.35–8.04; P = 0.009) as well as shorter time to appropriate antibiotic therapy and clinical cure (OR 1.49, 95% CI 1.02–2.20; P = 0.04). CRAB isolates were more likely to be susceptible to minocycline vs. tigecycline (83% vs. 18%, P = 0.003). Conclusion No differences were seen in ACIM, CC and LOS between dual vs. triple antibiotic groups. Minocycline tends to sustain better susceptibility toward CRAB vs. tigecycline. Elevated serum creatinine was found to be a predictor for ACIM while shorter time to appropriate antibiotic therapy was associated with CC. Disclosures All authors: No reported disclosures.


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