scholarly journals Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. Al-Kahtani ◽  
Ashraf M. Abdel-Moneim ◽  
Omar M. Elmenshawy ◽  
Mohamed A. El-Kersh

Background.The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats.Methods.The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology.Results.A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity.Conclusion.The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.

2021 ◽  
Vol 11 (9) ◽  
pp. 3981
Author(s):  
Mansour Alsharidah ◽  
Abdel-Moneim Hafez Abdel-Moneim ◽  
Ashwag Saleh Alsharidah ◽  
Mugahid A. Mobark ◽  
Arshad Husain Rahmani ◽  
...  

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.


2021 ◽  
Author(s):  
Alireza Najafizadeh ◽  
Ayat Kaeidi ◽  
Mohammadreza Rahmani ◽  
Elham Hakimizadeh ◽  
jalal Hassanshahi

Abstract Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has antioxidant effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in male rats. In this experimental study, forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10 mg/kg, acetaminophen, acetaminophen + carvacrol 5 mg/kg, and acetaminophen + carvacrol 10 mg/kg. Animals initially received a single dose of acetaminophen (500 mg/kg), then were treated with carvacrol for one week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10 mg/kg) could significantly increase the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05). Also, carvacrol significantly decreased the cleaved caspase-3, Bax proteins expression level, and also kidney tissue damage score in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05). This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress, apoptosis and its antioxidant effects.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiongwei Yu ◽  
Wenjun Han ◽  
Changli Wang ◽  
Daming Sui ◽  
Jinjun Bian ◽  
...  

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.


2011 ◽  
Vol 28 (7) ◽  
pp. 655-662 ◽  
Author(s):  
Mohamed Makni ◽  
Yassine Chtourou ◽  
Mohamed Barkallah ◽  
Hamadi Fetoui

This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl4) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl4 toxication groups received a single injection of CCl4 (1 ml/kg, i.p.; CCl4 and Va + CCl4 groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO2 and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl4 in rats.


2021 ◽  
Vol 74 (10) ◽  
pp. 2460-2462
Author(s):  
Seher Abdurasool Almedeny ◽  
Jabbar Yasir AL- Mayah ◽  
Mohanmed S. Abdulzahra ◽  
Najah R. Hadi

The aim: To evaluate the effect of single daily 25 mg of spironolactone on serum electrolytes and kidney function tests in patients with severe chronic left sided heart failure. Materials and methods: 60 patients with severe chronic left sided heart failure were enrolled in this study and they were divided in to 2 equal groups’ one group with standard therapy of HF and the other with spironolactone in a dose of 25 mg / day, as an additive therapy to the standard one. Serum electrolytes and kidney function tests were assessed at the beginning of the study and after 3 months. Results: A significant increment in serum potassium (p<0.05) was observed in the spironolactone group after 3 months treatment, while no significant reduction in serum sodium (p>0.05) and no significant increase in serum creatinine and blood urea (p>0.05) was noticed in the same group, control group showed no significant changes (p>0.05), in both serum electrolytes (S.K and S.Na) and renal function tests (S.C and B.U). Conclusions: Spironolactone caused a significant elevation of serum potassium level but this elevation is still with the clinically accepted ranges when low dose of spironolactone is used and with intact renal function. Serum creatinine level was not significantly increased with 25 mgl day of spironolactone. We conclude that Renal function tests namely blood urea and serum Creatinine, and serum potassium should be closely monitored in patients on spironolactone therapy especially those patients who use ACEI and ARBs in addition.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Zehui Jiang ◽  
Jun Zhang ◽  
Yuanan Lu

Objective. To explore the protective effect and mechanism of rosuvastatin on acute renal injury induced by a nonionic hypotonic contrast medium in rats. Methods. Forty-eight healthy adult SD rats were randomly divided into three groups: normal control group (NC); contrast medium control group (CM); and rosuvastatin intervention group (RI). The RI group was intragastrically administered with a 10 mg/kg of rosuvastatin 12 h prior to the contrast exposure. All rats in CM and RI groups were inoculated with 10 mL/kg of chemical (IV) while the same volume of saline for the NC group. At 24 h and 72 h posttreatments, pathomorphological changes of renal tubules were documented, respectively, and several biochemical indicators were tested to assess renal injury of experimental rats. Results. Compared with the CM group, rats in the RI group showed significantly reduced injury of kidneys and decreased levels of biochemical indicators such as blood Scr, blood Cys-C, urine NAG, urine α1-MG, and urine mALB. The serum Hs-CRP in the CM group increased significantly from 24 h to 72 h (p<0.05), but this was not observed in the rats of the RI group. In addition, SOD activity in the RI group was significantly increased (p<0.01) while SOD activity in renal tissue decreased significantly with time in the CM group (p<0.05). Conclusion. Short-term intervention with rosuvastatin can lead to reduced kidney damage associated with the contrast agent by reducing the levels of inflammatory factors and oxidative stress. Thus, rosuvastatin intervention has a protective effect on rats from contrast-induced nephropathy.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Guo Guang Wang ◽  
Xiao Hua Lu ◽  
Wei Li ◽  
Xue Zhao ◽  
Cui Zhang

Diabetic nephropathy is a long-term complication of diabetic mellitus. Many experimental evidences suggest that persistent hyperglycaemia generates intracellular reactive oxygen species (ROS) and upregulates transforming growth factor-b1 and extracellular matrix expression in mesangial and tubular epithelial cells, which is involved of free radicals in the pathogenesis of diabetes and more importantly in the development of diabetic complications. Antioxidants effectively inhibit high-glucose- and H2O2-induced transforming growth factor-b1 and fibronectin upregulation, thus providing evidence that ROS play an important role in high glucose-induced renal injury. The flavonoid luteolin has been shown to possess direct antioxidant activity, therefore we hypothesize that it may be useful in treatment of many chronic disease associated with oxidative stress, such as diabetic nephropathy via its antioxidant properties. Our results suggested that protection against development of diabetic nephropathy by luteolin treatment involved changes in superoxide dismutase (SOD) activity, the malondialdehyde (MDA) content and expression of Heme Oxygenase-1 (HO-1) protein.


2018 ◽  
Vol 30 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Abolfazl Khajavi Rad ◽  
Reza Mohebbati

Abstract Background Because of the antioxidant effects of Zataria multiflora (ZM) and carvacrol (CAR) and also the role of oxidative stress in the induction of cardiotoxicity induced by Adriamycin (ADR), the aim of this study was to investigate the improvement effects of ZM extract and CAR on cardiotoxicity induced by ADR in rats. Methods Twenty-eight male rats were randomly assigned to four groups including (1) the control group; (2) the ADR group, which received ADR intravenously at the beginning of the study and the (3) ZM+ADR and (4) CAR+ADR groups, which received ZM and CAR by gavage for 28 consecutive days and ADR as single dose. Blood samples were collected on days 0 and 28 to determine serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH). Also, cardiac tissue was removed for redox marker evaluation. Results In the ADR group, malondialdehyde (MDA) significantly increased and superoxide dismutase (SOD) activity and total thiol contents significantly reduced, as compared with the control group, while CAR administration significantly improved this condition. Treatment with ZM significantly increased the SOD activity and total thiol content, as compared with the ADR group. The level of LDH significantly increased on day 28 in the ADR group compared to the control group, and administration of ZM and CAR significantly decreased it. The SGPT and SGOT levels in the ADR group significantly increased, and CAR administration significantly reduced them. Conclusion The results indicate that the administration of ZM hydroalcoholic extracts and its active ingredient, CAR, could reduce the oxidative stress damage through promotion of the cardiac and systemic antioxidant system. Also, CAR administration demonstrated better improvement in cardiotoxicity with ADR in rats.


ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.


2020 ◽  
pp. 1-6
Author(s):  
Masoud Hosseinzadeh ◽  
Amir Alizadeh ◽  
Parnian Heydari ◽  
Marzieh Kafami ◽  
Mahmoud Hosseini ◽  
...  

Abstract Objective: Neurotoxicity is an adverse effect caused by cisplatin due to inflammation and oxidative stress in the central nervous system. The present study aimed to assess the effects of vitamin E injection on the learning and memory of rats with cisplatin-induced cognitive impairment. Methods: Male rats were administered with cisplatin (2 mg/kg/7 day; intraperitoneally [i i.p.]) and/or vitamin E (200 mg/kg/7 day; i.p.) for 1 week, and the control group received saline solution. Spatial memory was evaluated using Morris water maze (MWM). In addition, the hippocampal concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical methods. Results: According to the findings, cisplatin significantly increased the escape latency, while decreasing the time spent and travelled pathway in the target quadrant on the final trial day compared to the control group. Furthermore, pre-treatment with vitamin E significantly reversed all the results in the spatial memory test. The biochemical data indicated that vitamin E could decrease MDA activity and increase thiol and SOD activity compared to the control group. Conclusion: According to the results, vitamin E could improve cisplatin-induced memory impairment possibly through affecting the hippocampal oxidative status.


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