scholarly journals Thymoquinone, but Not Metformin, Protects against Gentamicin-Induced Nephrotoxicity and Renal Dysfunction in Rats

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.

2017 ◽  
Vol 40 (2) ◽  
pp. 77-81
Author(s):  
Zena M. Hamad

     Acetaminophen also called paracetamol is commonly used as analgesic and antipyretic agent which in high doses causes liver and kidney damage in man and animals. Nigella sativa oil have antioxidant properties. Thirty adult male rats were used and randomly divided into three equal groups. Group (A) untreated and served as control group; Group (B) rats were orally intubated (by gavages needle) acetaminophen suspension (150mg/kg B.W). Group (C) rats were given orally acetaminophen suspension (150mg/kg) plus 1ml/kg B.W of Nigella sativa oil for 42 days in both treated group. Fasting blood samples were collected at 21 and 42 days of experiment to study the following parameters:  Serum creatinine concentration and blood urea nitrogen concentration. The results revealed a significant increase of acetaminophen group in serum creatinine and blood urea nitrogen concentrations as compression with GA. Animals treated with Nigella sativa oil plus acetaminophen (C) showed a significant decline in serum creatinine and blood urea nitrogen concentrations. In conclusion, the acetaminophen was effective in induction of oxidative stress and change in some biological markers related to kidney disease. Also it seems that Nigella sativa oil exerts protective actions against the damaging effect of acetaminophen


2020 ◽  
Vol 10 ◽  
Author(s):  
Amel Amrani ◽  
Ouahiba Benaissa ◽  
Nassima Boubekri ◽  
Fadila Benayache ◽  
Samir Benayache ◽  
...  

Background: Long-term administration of valproic acid (VPA) is known to promote renal tubular injury mediated by increase in renal oxidative stress. Recent evidence indicates that natural antioxidants are alternative to attenuate oxidative stress and kidney damage. Objective: This study was performed to investigate the protective effects of n-butanol extract of Rhanterium suaveolens, vitamin E (Vit E) and vitamin C (Vit C) against VPA induced nephrotoxicity in mice. Methods: Mice were randomly divided into 6 groups (n: 8) and treated daily for 12 days. They received VPA (300 mg/kg intraperitoneally (ip)), buthanolic extract (100 mg/kg), Vit E (100 mg/kg), and Vit C (16.66 mg/kg) 1h prior to administration of VPA. On day 13, blood and Kidneys samples were analyzed for biomarker levels and histopathological changes. Kidneys homogenates were used for determination of oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level and glutathione peroxidase (GPx) activity. Result: Treatment with VPA showed a significant increase in the levels of serum creatinine, urea and malondialdehyde (MDA) and decreasing the enzymatic activity (GPx) as well as GSH levels in kidney with marked necrotic epithelial cells and infiltration in kidney sections as compared to the control group. Pretreatment with the n-butanol extract of R. suaveolens, Vit C or Vit E 1 h prior to administration of VPA showed a significant decrease in the levels of serum creatinine, urea, and MDA, as well as an improvement in the antioxidant elements and histological changes compared to those previously seen in the group treated with VPA alone. Conclusion: It is concluded that n-butanol extract of R. suaveolens, Vit C and Vit E pretreatment effectively improved renal function and tissue oxidative damage caused by VPA.


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.


Author(s):  
FAJAR APOLLO SINAGA ◽  
URIP HARAHAP ◽  
JANSEN SILALAHI ◽  
HERBERT SIPAHUTAR

Objective: The purpose of this study was to determine the protective effects of virgin coconut oil (VCO) treatment on hepatic oxidative stress and antioxidant defenses after maximum physical activity. Methods: This study used 24 healthy male rats. The rats were divided into four groups randomly consisted of six rats in each group. The control group (P0) was given 2 mL water, the treatment groups (VCO-1, VCO-2, and VCO-4) were given VCO 1 ml/200 g BW, 2 ml/200 g BW, and 4 ml/200 g BW, respectively, per day using gavage spuit. The rats were trained to swim for a month, 30 min/day in the 1st week, 35 min/day in the 2nd week, 40 min/ day in the 3rd week, and 45 min/day in the 4th week. After 28 days, the rats were forced to perform the maximal activity by putting the rats in water with no exit. Blood samples were collected immediately after the maximum physical activity, and then, all rats were killed and liver tissues were collected. The malondialdehyde (MDA), glutathione peroxidase (GPx), and serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvate transaminase level were then measured. Results: VCO increased swimming time to exhaustion, levels of GPx in the liver, which were accompanied by corresponding decreases in the MDA, alanine transaminase, and aspartate transaminase content. Conclusion: The results from this study indicate that VCO is effective in the prevention of oxidative stress following maximum physical activity.


2020 ◽  
Vol 11 (03) ◽  
pp. 430-434
Author(s):  
Shaymaa J. Shamran ◽  
Haider S. Jaffat

The current study was designed to determine the antioxidant effects of vitamin C and vitamin E against oxidative stress induced by vancomycin in some antioxidants changes in the male rats. The study was conducted in the animal house of the Faculty of Science/University of Kufa for the period from April, 2018 to May, 2018 on 119 animals of male rats aged 2.5–3 months and the weight of 150-200 gm. Two experiments designed in this study addressed the first and two experiments to study the oxidative effect of vancomycin in addition to the protective effects of vitamin C and vitamin E to reduce these effects in the treatment of animals for one week and three weeks with vancomycin and vancomycin plus vitamins. The results indicated a significant increase (p less than 0.05) in the MDA, CAT, and significant decrease (p less than 0.05) in SOD, and GPX. In the animals treated with vancomycin 40,60 mg/kg only compared to the control group for the two periods of administration at the same time occur a significant decrease(p less than 0.05) in the MDA, CAT and a significant increase (p less than 0.05) in the SOD and GPX after treated animals with vancomycin 40,60 mg/kg with vitamin C and vitamin E for a period of one and three weeks compared with vancomycin group.


Author(s):  
Radja Djebbari ◽  
Yasmine Chemam ◽  
Nassima Boubekri ◽  
Zohra Lakroun ◽  
Mohammed Kebieche ◽  
...  

The objective of the current study was led to reveal the possible protective effects of n-butanol extract of Helianthemum confertum (H. confertum) against doxorubicin (DOX) induced liver damage and its implication on the integrity of liver cells. Adult male rats were randomly divided into groups treated with plant extract (50 mg/kg, 100 mg/kg) for 10 days and/or injected with a single dose of DOX (10 mg/kg). Liver function as well as oxidative stress parameters and histological study were estimated. DOX treated rat’s induced hepatic dysfunction revealed by a significant increase in biochemical parameters (serum transaminases, cholesterol and triglycerides) and disturbance in oxidative stress parameters described by an increase in malondialdehyde (MDA) levels, providing information on the loss of cellular integrity. This later elicited histopathological changes in the liver which was confirmed on histological section chowing necrotic cells. Altghout the DOX-treatment reduced significantly the reduced glutathione (GSH) level and the glutathione peroxidase (GPx) activity. The pretreatment of the animals with n-butanol extract of H. confertumat 50 mg/kg and 100 mg/kg counteracted almost all adverse effects induced by DOX. The results showed a considerable decrease in serum markers of liver function and lipid peroxides. There was significant increase in the GSH level and the activity of antioxidant enzyme (GPx), which allowed the normalization of redox status in liver cells. Data suggest that DOX-induced an oxidative stress in rat’s liver and nbutanol extract of H. confertum exerted antioxidant properties.


2020 ◽  
Vol 39 (8) ◽  
pp. 1066-1078 ◽  
Author(s):  
EM El Morsy ◽  
MAE Ahmed

Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.


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.


Author(s):  
Fahime Sadat Kamali ◽  
Rasoul Shahrooz ◽  
Golamreza Najafi ◽  
Mazdak Razi

Background: Paraquat (PQ), as a pyridine compound, is widely used worldwide to control annual weeds. The oxidative stress caused by PQ can cause deleterious changes in the testicular tissue. Objective: An investigation on the protective effects of Crocin (CCN) against PQinduced oxidative damages and apoptotic indices in testicular tissue. Materials and Methods: Twenty-eight adult male albino mice (20-25 gr) were divided into four groups (n = 7/each). The control group received 0.1 ml/day of normal saline by intraperitoneal injection (IP); sham-control group received PQ 5 mg/kg/day, IP, and the experimental groups received PQ (CCN+PQ) and CCN-sole (200 mg/kg/day, IP), respectively, for 35 continuous days. At the end of the treatment period, the testes were dissected out and used for biochemical, molecular, and histological analyses. The expressions of tumor suppressor p53, B-cell lymphoma 2 (bcl-2), and caspase-3 were considered as hallmark factors of mitochondria-dependent apoptosis. Moreover, the testicular superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated as key biomarkers for oxidative stress. Results: The PQ significantly (p < 0.02, p < 0.01) diminished the spermatogenesis indices and SOD, increased MDA levels, and enhanced the apoptosis-related gene expression. However, the co-administration of CCN and PQ significantly (p < 0.01, p < 0.01, p < 0.02) ameliorated the spermatogenesis ratio, upregulated the SOD level as well as bcl-2 expression, and reduced the MDA content and apoptosis vs the PQ-sole group. Conclusion: This study showed that the antioxidant properties of CCN enable to ameliorate the PQ-induced destructive effects by upregulating the testicular structure, antioxidant and apoptotic status. Key words: Histology, Testis, Paraquat, Crocin, Mice.


2020 ◽  
Vol 1 (2) ◽  
pp. 72-75
Author(s):  
Sajjad Makhdoomi ◽  
Akram Oftade ◽  
Sodabe Khodabandehlou ◽  
Akram Ranjbar

Background: The present study was performed to investigate the protective effects of propofol against cisplatin-induced pulmonary toxicity in rats. Methods: A total of 20 male Wistar rats weighing 180-250 g were divided into four groups of control, the cisplatin-intoxicated group intraperitoneally (IP) injected with cisplatin (7 mg/kg/d for a week), the propofol group (10 mg/kg/d, IP), and the protected group receiving propofol (10 mg/kg/d, IP) poisoned by cisplatin. Then, the biomarkers of total antioxidant capacity (TAC), catalase (CAT) activity, and lipid peroxidation (LPO) were measured in homogeneous lung tissues. Results: The data revealed the evidence of oxidative stress in the lung tissue of cisplatin-intoxicated rats as indicated by an increase in the level of LPO compared with propofol and protected groups (P<0.05). Moreover, TAC decreased in the cisplatin group while it increased in the propofol group compared to cisplatin and protected groups (P<0.05). No significant difference was observed between the groups regarding CAT (P>0.05). Protection with propofol ameliorated the oxidative stress induced by cisplatin in the lung tissue because of the reduction of LPO. Conclusion: According to these results, it seems that propofol provides a remarkable protection against cisplatin-induced oxidative pulmonary damage mediated by its antioxidant properties.


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