scholarly journals The Protective Effect of Carvacrol on Acetaminophen-Induced Renal Damage in Male Rats

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.

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 ◽  
Author(s):  
FAHRIYE ZEMHERI NAVRUZ ◽  
Sinan INCE ◽  
Damla ARSLAN-ACAROZ ◽  
Ulaş ACAROZ ◽  
Hasan Hüseyin DEMIREL ◽  
...  

Abstract Pyraclostrobin (Pyra) is a fungicide in the strobilurin class and has proven to be very toxic to aquatic species. Resveratrol (Res) is a phytoalexin that exhibits multiple bioactivities as antioxidative, anti-inflammatory, cardiovascular protective, and anti-aging in animals and is found in plant species such as mulberry, peanut, and grape. This study aimed to determine the protective effect of Res against Pyra-induced oxidative stress in rats. For this purpose, a total of 48 male rats divided into 6 groups − 8 in each group - were exposed to 30 mg/kg Pyra by oral gavage once a day for 4 weeks and to 3 different concentrations of Res (5, 10 and 20 mg/kg) together with Pyra. It was observed that, in groups administered with Pyra, malondialdehyde (MDA) levels increased whereas glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels decreased. It was observed that, in the group administered with Pyra, expression levels of CYP2E1 gene, which is associated with increased cancer risk, pro-apoptotic BAX gene, apoptotic caspase-3, caspase-8 and caspase-9 genes, NFκB gene, which is a pro-inflammatory transcription factor, and p53 gene, which plays a regulatory role in the cell, increased whereas expression level of anti-apoptotic bcl-2 gene decreased. It was determined that Res administrations improved Pyra-induced oxidative damage, histopathological changes and expression levels of various genes. According to the ssDNA analysis obtained from the DNA isolated from the blood; when DNA damage and histopathological damage in tissues were examined, it was observed that the highest damage was in the group administered with Pyra and the damage decreased depending on the increase in dose of Res. Consequently, it was observed that Res, known for its antioxidant protective properties, exhibited a protective effect against oxidative stress caused by Pyra.


2016 ◽  
Vol 36 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Yasemin Yuksel ◽  
Ramazan Yuksel ◽  
Murat Yagmurca ◽  
Hacer Haltas ◽  
Husamettin Erdamar ◽  
...  

Objective: This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies. Methods: Twenty-four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin–eosin and periodic acid–Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples. Results: Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression ( p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase-3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx. Conclusion: As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity.


2008 ◽  
Vol 31 (4) ◽  
pp. 212 ◽  
Author(s):  
Wei-De Zhong ◽  
Hui-Chan He ◽  
Ru-Biao Ou ◽  
Xue-Cheng Bi ◽  
Qi-Shan Dai ◽  
...  

Purpose: To investigate the protective effect of ganoderan on renal damage in rat models with chronic glomerulonephritis induced by adriamycin. Methods: 48 healthy Sprague-Dawley rats were randomly divided into three groups: control, nephritic model and ganoderan treatment groups. Changes of the following indices in the three groups were observed 6 weeks after treatment: 24-hour urine protein, albumen, serum creatinine, cholesterol. Histopathological observations of the renal cortex were made by light and electron microscopy. Results: Compared with controls, levels of 24-hour urine protein (9.60±0.57mg/d vs. 82.50±3.18mg/d), serum creatinine (35.25±2.63?mol/L vs. 44.75±8.06?mol/L) and cholesterol (1.15±0.10mmol/L vs. 4.02±0.25mmol/L) of rats in the nephritic model group were increased (P < 0.05), and the concentration of albumen was decreased (35.98±1.34g/L vs. 19.05±0.62g/L, P < 0.05). Ganoderan administration decreased 24-hour urine protein (82.50±3.18mg/d vs. 45.01±3.94mg/d, P < 0.05). Following ganoderan, the pathological changes in kidney tissue were improved compared with those in the nephritic model group. Conclusion: Ganoderan exerts protective effects in rats with chronic glomerulonephritis induced by ADR. Ganoderan reduced 24-hour urine protein, serum creatinine, cholesterol, improving renal function and reducing the severity of renal injury.


2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.


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

2018 ◽  
Vol 30 (2) ◽  
pp. 205-217 ◽  
Author(s):  
Bisi O. Adeoye ◽  
Ademola A. Oyagbemi ◽  
Ebunoluwa R. Asenuga ◽  
Temidayo O. Omobowale ◽  
Adeolu A. Adedapo

Abstract Background Cisplatin (CP) is a novel drug of choice in the treatment of cancer but its major limitation is nephrotoxicity, which is dose limiting. Andrographis paniculata (AP) is a common Indian dietary component. It is well known for its medicinal properties. This present study investigated the nephroprotective effect of ethanol leaf extract of Andrographis paniculata (EEAP) on CP-induced nephrotoxicity. Methods CP was used to induce nephrotoxicity in male Wistar rats to study the effect of EEAP on renal damages using hematological parameters, biochemical parameters, histology, and immunohistochemistry studies. Results The effects of EEAP were determined by CP-induced changes in different kidney tissue on antioxidant enzymes, markers of oxidative stress, serum creatinine, and urine parameters. Administration of EEAP (200 mL/kg and 400 mg/kg orally), prior to and following a single dose CP treatment (10 mg/kg i.p), significantly mitigated the CP-induced decrease in antioxidant enzymes, and increase in markers of oxidative stress, serum creatinine, and urinary protein. On histopathological examination of the kidney tissue, there was severe glomerular degeneration and infiltration of inflammatory cells in CP only treated rats, mild glomerular degeneration, and infiltration of inflammatory cells in EEAP pre-treated rats. Furthermore, EEAP activated Nrf2 and mitigated Kim-1 pathways in CP-induced nephrotoxicity. Conclusions The results showed the protective effect of EEAP against CP-induced nephrotoxicity.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Ayed A. Shati ◽  
Mohamed Samir A. Zaki ◽  
Youssef A. Alqahtani ◽  
Mohamed A. Haidara ◽  
Mubarak Al-Shraim ◽  
...  

Insecticides and toxicants abound in nature, posing a health risk to humans. Concurrent exposure to many environmental contaminants has been demonstrated to harm myocardial performance and reduce cardiac oxidative stress. The purpose of this research was to study the protective effect of vitamin C (Vit C) on quinalphos (QP)-induced cardiac tissue damage in rats. Eighteen albino male rats were randomly categorised into three groups (n = 6). Control, QP group: rats received distilled water. QP insecticide treatment: an oral administration of QP incorporated in drinking water. QP + Vit C group: rats received QP and Vit C. All the experiments were conducted for ten days. Decline of cardiac antioxidant biomarkers catalase (CAT) and reduced glutathione (GPx) along with increased proinflammatory markers tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) indicated oxidative and inflammatory damage to the heart following administration of QP when compared to control rats. The light microscopic and ultrastructure appearance of QP-treated cardiomyocytes exhibited cardiac damage. Administration of Vit C showed decreased oxidative and inflammatory biomarkers, confirmed with histological and electron microscopic examination. In conclusion, Vit C protected the heart from QP-induced cardiac damage due to decreased inflammation and oxidative stress.


2018 ◽  
Vol 37 (4) ◽  
pp. 285-295 ◽  
Author(s):  
Gabriel A. Dedeke ◽  
Folarin O. Owagboriaye ◽  
Kehinde O. Ademolu ◽  
Olanrewaju O. Olujimi ◽  
Adeyinka A. Aladesida

There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate. We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat. Fifty-six adult male rats randomized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3.6, 50.4, and 248.4 mg/kg body weight (bw) of glyphosate concentrations for 12 weeks with distilled water administered to the control group. Kidney biomarker (serum urea and creatinine, plasma cystatin-C, and neutrophil gelatinase-associated lipocalin), oxidative stress indices in the kidney tissue, activities of kidney membrane-bound enzymes (Mg-adenosine triphosphatase [ATPase], Ca-ATPase, Na/K-ATPase, and total ATPase), and histopathological changes in the kidney were monitored. Glyphosate concentration in the kidney was quantified by high-performance liquid chromatography with ultraviolet detection. Significant ( P < 0.05) alterations in the levels of the kidney biomarker, oxidative stress markers, and membrane-bound enzymes were observed in the rats exposed to Roundup compared to the rats exposed to glyphosate alone. Rats exposed to Roundup accumulated more glyphosate residue in their kidney tissue. Severe histopathological lesions were only seen in the kidneys of rats exposed to Roundup. The nephrotoxicity observed cannot be due to the active ingredient in the Roundup formulation, as glyphosate alone has virtually no effect on the renal function of the exposed animals. Therefore, the general claim attributing nephrotoxicity of a glyphosate-based herbicide to its active ingredient should be discouraged.


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.


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