Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (Viscum album L.) Extract

2017 ◽  
Vol 24 (6) ◽  
pp. 364-370 ◽  
Author(s):  
Esin Sakalli Çetin ◽  
Hasan Tetiker ◽  
Özgür İlhan Çelik ◽  
Nigar Yılmaz ◽  
İbrahim Hakkı Ciğerci

Background: The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay. Material and Methods: 32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out. Results: MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly. Conclusion: This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.

Author(s):  
Auwal Balarabe Bello ◽  
Mudassir Lawal ◽  
A. Muhammad Hisbullahi

Aim: The aim of this study is to compare the protective effect of zinc nanoparticle and zinc supplement against carbamazepine induced reproductive changes in male Albino rats. Study Design: In this experiment, 60 Male albino rats were used which are divided into six groups of 10 rats each. The first group was used as the control for the experiment and they were given distilled water. The second Group, Group 2 were administered with 20 mg/kg body weight of carbamazepine, group 3 were administered with 20 mg/kg of carbamazepine plus 10 mg/kg of zinc nanoparticle and Group 4 were administered with 20 mg/kg of carbamazepine plus 10 mg/kg of zinc supplement while group 5 were administered with 10 mg/kg of zinc nanoparticle and also group 6 were administered with 10 mg/kg of zinc supplement only. Place and Duration of Study: Department of Biochemistry, Bells University of technology, Ota, Ogun State Nigeria, the research was carried out from February to June, 2018. Methodology: Zinc nanoparticle extraction was carried out to obtained Zinc nanoparticle. A 60 male albino rats with weight ranging from 140 g - 230 g were used. They were fed with normal rat chow and were allowed to acclimatize for a period of two weeks. They were then divided into six groups according to their body weight which contained the test groups and the control group. The rats were sacrificed after two weeks of test administration. They were allowed an overnight fast (24 hours). The cervical dislocation was done, and the blood was collected from the heart, in to a lithium heparinized bottle. The testes of the rats were also collected and stored in a sample bottle containing buffer and stored, the liver, kidney and the brain were collected too. The rats liver and testes were weight and macerated in 5 times the volume of the actual organ weight using homogenate buffer (phosphate buffer). The resulting homogenate was centrifuge at 10000 rmp speed for 15 mins then it was removed from the centrifuge and the supernatant was decanted and stored below 4°C. Result: The group administered with carbamazepine only show significant decreased in the level of follicle stimulating hormone, luteinizing hormone and testosterone when compared with control group, followed by the group administered with zinc nanoparticle only. However, group 6 and group 4 that were administered with zinc supplement and zinc supplement plus carbamazepine showed a significant increase in the level of these hormones when compared with control group, while group 6 which were administered with carbamazepine and zinc nanoparticle showed no significant different when compared with control group. In addition carbamazepine alone significantly increased the level of alanine transaminase (ALT) in the liver and also the group administered with zinc nanoparticle alone significantly increased the level of aspartate transaminase (AST) with decrease in the level of ALT. However, the groups administered with zinc supplement alone and in combination with carbamazepine reduced ALT and AST levels in the liver. Conclusion: Therefore, this study suggest that, carbamazepine induced toxicity by affecting the level of sex hormones and activities of the kidney in the male albino rats, and also zinc nanoparticle have more protective effect than zinc supplement against carbamazepine toxicity.


2020 ◽  
Vol 71 (1) ◽  
pp. 1997
Author(s):  
M. DÜZ ◽  
A. F. FIDAN

The present study was carried out to determine the effects of sub-chronic thinner addiction on the oxidant-antioxidant balance and oxidative stress on certain tissues and the possible protective effect of safranal against thinner toxication in rats. Adult male Wistar albino rats were randomly divided into four groups of 10 animals each as follows: control (C), safranal (S), thinner (T) and thinner+safranal (T+S). The control group received 1cc saline by gastric gavage. Safranal was administered to S and T+S groups by using gastric gavage at a dose of 100 mg/kg/day and volume of 0.1 mL/kg/day. Thinner inhalation was applied to T and T+S groups in a container with NaOH tablets twice a day. Levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NOx) metabolites, total antioxidant capacity (TAS) and total oxidant capacity (TOS) were determined in liver, lung, brain, kidney and testis tissues of the rats. In the T+S group, it was observed that the MDA levels significantly decreased in all tissues, except the kidney, in comparison to the thinner inhalation group (p = 0.000). When the NOx levels of the T+S group were compared with the levels of the T group, it was concluded that there existed a statistically significant decrease in the NOx levels in alltissues (p = 0.000). In T+S group, it was observed that safranal either eliminated or mitigated oxidative stress that developed in tissues through decreasing MDA and TOS levels and increasing GSH and TAS levels and caused significant decreases in NOX levels in all tissues. As a result, it was determined that safranal, although not uniform for all tissue types, had a protective potential against the damaging effects of oxidative stress caused by sub-chronic thinner inhalation.


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.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ismail Koyuncu ◽  
Abdurrahim Kocyigit ◽  
Ataman Gonel ◽  
Erkan Arslan ◽  
Mustafa Durgun

The aim of this study is to examine the protective effect of naringenin-oxime (NOX) on cisplatin-induced major organ toxicity and DNA damage in rats. Thirty-five male Wistar albino rats were equally split into five groups as follows: control (i.p., 0.1 ml of saline), Cis administration (i.p., 7 mg/kg b.w.), NOX treatment (i.p., 20 mg/kg b.w., daily for ten days), Cis + NOX20, and Cis + NOX40 combination (i.p., 20 and 40 mg/kg b.w., daily for ten days). Serum and peripheral blood mononuclear leukocytes (PBMC) were obtained from blood. Malondialdehyde, glutathione, total antioxidant and oxidant status, and catalase were measured in serum, liver, and kidney, and oxidative stress index was calculated. In parallel, paraoxonase and arylesterase activities were tested in liver and serum. We used 8-OHdOG as a marker for DNA damage in serum via ELISA and in PMBC via comet assay. Treatment with Cis elevated the levels of serum biochemical parameters, oxidative stress, and DNA damage. Pretreatments of NOX restored biochemical and oxidative stress parameters in serum, renal, and liver tissues (p<0.01) and reduced 8-OHdG level, a finding further supported by comet assay in PBMC. Observations of the present study support the fact that treatment with NOX prevents Cis-induced hepatotoxicity, nephrotoxicity, and genotoxicity by restoring antioxidant system.


2018 ◽  
Vol 1 (3) ◽  
pp. 20-31 ◽  
Author(s):  
Amal A Halawa ◽  
Mohamed A El-Adl ◽  
Mohamed F Hamed ◽  
Ahmed Z Balboula ◽  
Mohammed A Elmetwally

Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.


2021 ◽  
Vol 8 (8) ◽  
pp. 475-479
Author(s):  
Deniz Dirik ◽  
Ahmet Ufuk Komuroglu

Objective: Aspirin is a non-steroidal anti-inflammatory drug with antioxidative properties. It is recommended to use different doses and durations according to the characteristics of the patient and the type of disease. Therefore, in this study, we aimed to investigate the effect of using aspirin at different doses and for different durations on oxidative stress in ovarian tissue. Material and Methods: Female Wistar albino rats were divided into five groups. Group 1: control group, no special treatment was applied to the rats in this group. Group 2: 1 mg/kg aspirin was administered orally to the rats in this group every day for 28 days. Group 3: 3 mg/kg aspirin was administered orally to rats in this group every three days. Ggroup 4: 5 mg/kg aspirin was administered orally to rats in this group every five days. Group 5: 7 mg/kg aspirin was administered orally to the rats in this group once a week. After fasting overnight following the last application, the rats were sacrificed, and their ovarian tissues were collected. Malondialdehyde, catalase, total thiol group, and AOPP levels were studied from ovarian tissue. Results: Group4 and group5 ovarian tissue MDA levels were found to be significantly higher than the other groups (p<0.05). There was no significant difference between group1, group2 and group3 ovarian tissue MDA levels (p>0.05). Group1 (control group) ovarian tissue AOPP level was found to be significantly lower than all aspirin-administered groups (p<0.05). Group2 ovarian tissue AOPP level was found to be significantly lower than group3, group4 and group5 (p<0.05). TSG level was found to be significantly higher in group 5 when compared to other groups (p0<0.05). Group4 ovarian tissue TSG level was found to be significantly higher when compared to group1, group2 and group3 (p<0.05). Group3 and group4 ovarian tissue CAT activity was found to be significantly higher than group1, group2 and group5 (p<0.05). When group1, group2 and group5 ovarian tissue CAT activities were compared, no significant difference was found (p>0.05). Conclusion: The application of aspirin at certain intervals rather than daily application may have more positive effects on the antioxidant system. especially taking aspirin at intervals of 3 or 5 days may be more effective


2021 ◽  
Vol 25 (1) ◽  
pp. 154-172
Author(s):  
K. K. Khudiar ◽  
B. N. Abdullah ◽  
K. A. Al-Mzaien

In this study, the potential protective effect of aqueous extract of parsley (Petroselinum sativum) seeds against hydrogen peroxide (H2O2) – induced oxidative stress in male rats was assessed. Three groups of male albino rats were randomly divided (n=7) and were handled for twenty-eight days as follows: rats in group I served as control; animals in group || were provided with drinking water containing 0.5% H2O2 and those in group III received orally 8 mg/100 gm B.W. of aqueous extract of parsley seeds plus 0.5% H2O2 in drinking water. After four weeks experimental period, a significant increase in lipid peroxidation products (MDA), and decrease in glutathione (GSH) concentrations were observed in plasma, kidney, liver and heart tissues of H2O2 treated animals as compared with the control group. These biomarkers (GSH and MDA) are interrelated and indicate the occurrence of oxidative stress. Plasma total cholesterol (TC) concentration was significantly increased in H2O2 treated rats. By administration of aqueous extract of parsley along with H2O2, plasma and tissue GSH levels were significantly increased while the elevation in MDA level was diminished in plasma and different tissues examined. A decrease in plasma cholesterol concentration was recorded in H2O2 and parsley treated group as compared with the control one and H2O2 treated groups. These results indicate that aqueous extract of parsley have hypocholesterolemic and antioxidant effect.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1332
Author(s):  
Gilda M. Iova ◽  
Horia Calniceanu ◽  
Adelina Popa ◽  
Camelia A. Szuhanek ◽  
Olivia Marcu ◽  
...  

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.


2021 ◽  
Vol 18 ◽  
Author(s):  
Yuan Li ◽  
Lan Chu ◽  
Chunfeng Liu ◽  
Zongyi Zha ◽  
Yuanlu Shu

Aim: This study investigated the protective effect of dimethyl fumarate (DMF) in rats by mediating GSK3-β/Nrf2 using the middle cerebral artery embolization reperfusion (MCAO/R) rat model. Background: After an acute ischemic stroke (AIS), oxidative stress occurs. Dimethyl fumarate (DMF), a nuclear factor-E2-related factor 2 (Nrf2) activator, approved by the US Food and Drug Administration (FDA), was observed to regulate the Nrf2 pathway by acting as an anti-oxidative stress agent; however, whether this agent is involved in inhibiting GSK-3β remains to be established. Methods: DMF model was used to explore the effects of GSK-3β on Nrf2 expression level, Nrf2-ARE binding activity and Nrf2/ARE downstream expression level of anti-oxidant stress protein in Cerebral ischemia-reperfusion injury (CIRI). 60 rats were randomly divided into Sham group, MCAO/R group, solvent control group (DMSO group) and DMF treatment group, with 15 rats in each group. The MCAO/R, DMSO and DMF groups were considered in the MCAO/R model using the modified thread embolization method. In contrast, the Sham group was only anaesthetized and disinfected, and tissue muscle was dissected without inserting suture emboli. DMF group was gavaged with 45mg/kg per day of DMF, DMSO control group was gavaged with DMSO of equal volume, while MCAO/R group was only modeled without any intragastric treatment. The rats were treated seven days after the operation, and a neurological function Longa score was estimated. The rats were sacrificed seven days later, and the infarct volume was assessed by TTC staining. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in rat brain tissue. Nissl staining was used to observe the expression of neurons in the infarcted cortex. Western blotting (WB) was used to observe the protein expression levels of glycogen synthase kinase 3β(GSK-3β), nuclear factor E2-related factor 2 (Nrf2), downstream heme oxygenase 1 (HO1) and NADPH quinone oxidoreductase 1 (NQO1) in four groups. The expression levels of GSK-3β and Nrf2 in the four groups were observed by immunohistochemistry and immunofluorescence. Results: (1) The Longa score of the MCAO/R, DMSO and DMF groups was found to be higher compared to the Sham group, indicating successful operation. The Longa score of the DMF group was lower than that of the other three groups 4-7 days after surgery (P<0.05). (2) HE and Nissl staining showed that the DMF group had lower neuron necrosis and higher gliosis compared to the control groups. (3) TTC staining results showed that the infarct volume of the DMF group was significantly smaller than the MCAO/R and DMSO groups. (4) Protein results showed that the GSK-3β expression in the DMF group was lower than that in all groups, while the expression of Nrf2, HO1 and NQO1 was higher compared to other groups. Conclusion: DMF can reduce neurological deficits and infarct size in the MCAO/R model. The protective effect may be related to decreased GSK-3β expression and increased Nrf2 expression, which may play a role in anti-oxidative stress.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


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