scholarly journals Protective Effect of Boswellic Acids against Doxorubicin-Induced Hepatotoxicity: Impact on Nrf2/HO-1 Defense Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bassant M. Barakat ◽  
Hebatalla I. Ahmed ◽  
Hoda I. Bahr ◽  
Alaaeldeen M. Elbahaie

The current study aimed to investigate the potential protective role of boswellic acids (BAs) against doxorubicin- (DOX-) induced hepatotoxicity. Also, the possible mechanisms underlying this protection; antioxidant, as well as the modulatory effect on the Nrf2 transcription factor/hem oxygenase-1 (Nrf2/HO-1) pathway in liver tissues, was investigated. Animals were allocated to five groups: group 1: the saline control, group 2: the DOX group, animals received DOX (6 mg/kg, i.p.) weekly for a period of three weeks, and groups 3–5: animals received DOX (6 mg/kg, i.p.) weekly and received protective doses of BAs (125, 250, and 500 mg/kg/day). Treatment with BAs significantly improved the altered liver enzyme activities and oxidative stress markers. This was coupled with significant improvement in liver histopathological features. BAs increased the Nrf2 and HO-1 expression, which provided protection against DOX-induced oxidative insult. The present results demonstrated that BAs appear to scavenge ROS and inhibit lipid peroxidation and DNA damage of DOX-induced hepatotoxicity. The antioxidant efficacy of BAs might arise from its modulation of the Nrf2/HO-1 pathway and thereby protected liver from DOX-induced oxidative injury.

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.


1990 ◽  
Vol 258 (4) ◽  
pp. F1026-F1035 ◽  
Author(s):  
B. J. Tucker ◽  
R. C. Blantz

Prostaglandins (PG) and angiotensin II (ANG II) contribute to regulation of glomerular microcirculation. Acute vs. chronic physiological alterations of glomerular hemodynamics that result from inhibition of either PG or ANG II, or both, and their interaction were examined. Four groups of Munich-Wistar rats were submitted to the following micropuncture studies in euvolemic conditions for measurements of glomerular hemodynamics and tubular fluid reabsorption: 1) an untreated control group, 2) 4- to 6-day inhibition of both PG and angiotensin-converting enzyme activity with meclofenamate and MK-421 (enalapril), 3) 4- to 6-day treatment with enalapril followed by acute PG inhibition in the second measurement period, 4) 4- to 6-day PG inhibition followed by acute enalapril treatment in the second period. Dual 4- to 6-day treatment decreased single-nephron filtration rate (SNGFR, 24 +/- 2 vs. 33 +/- 2 nl/min in control; P less than 0.05) as a result of decreases in single-nephron plasma flow (SNPF) and glomerular hydrostatic pressure gradient (delta P). Treatment with enalapril alone for 4-6 days did not reduce SNGFR and SNPF; however, delta P decreased. Acute addition of meclofenamate did not alter these factors. SNGFR was decreased with 4- to 6-day treatment of meclofenamate from 33 +/- 2 in control to 25 +/- 1 nl/min (P less than 0.05). Acute treatment with enalapril in the 4- to 6-day meclofenamate-treated rats increased SNGFR to values not different from control. The results demonstrated that glomerular hemodynamic alterations consequent to inhibition of ANG II and PG systems differ between chronic and acute treatments. Therefore, interpretation of the role of individual hormonal systems in the control of glomerular hemodynamics should be approached with caution, since effects may be altered by duration of treatment and involvement of other vasoactive systems.


Author(s):  
HANAA SALMAN KHADHEM ◽  
MAHDI MTHUWAINI ◽  
WAJDY J. MAJID

Objective: Pulmonary fibrosis (PF) is an irreversible and untreatable human disease encompasses a large group of chronic lung disorders associated with excessive remodeling, scarring, and fibrosis. The current work was designed to study the harmful effects of methotrexate (MTX) administration on the lung and the possible protective role of Carthmus tinctorius leaves extract. The animals were utilized in this study. Methods: A total of 40 male healthy adult Wistar albino rats with anaverage body weight of 200±25 g, were divided into four groups (10 animals each). G1: control group, G2: MTX group, G3: Carthamus tinctorius (CT), group G4:MTX+Carthamus tinctorius(CT). CT was administered orally at a dose of (40 mg/kg/day) for 4 w to G3 and G4. The (CT) group were performed to explore any toxic effect of the (CT) extract on the lung. Rats of G2 and G4 administered 4 mg/kg dose of MTX orally for 28 d. Rats of G1 were intraperitoneally (i. p) administered with normal saline 0.5 ml ∕ day for four weeks (4wk) to serveas control. The animals were weighed at the beginning, though, and at the end of experiments. Results: The study showed that the relative lung weight was significantly increased at (P˂0.01) in MTX-treated animals in comparison to the control group. A combination of CT extract with MTX revealed significant decrease (P<0.01) in the lung relative weight in comparison to MTX group. Histopathological examination revealed that lung injury was less severe in group 3 and 4compared to group 2. The results indicated that CT significantly decreased collagen deposition, hydroxyproline content, and ameliorated pathological changes. Conclusion: The study has clearly identified the importance protective role of CT extract on pulmonary fibrosis induced by methoxerate. We recommended CT as one of therapeutic strategy to amelioratethe lung fibrosis associated with methotrexate therapy.


2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.


2020 ◽  
Vol 1 (1) ◽  
pp. 10-14
Author(s):  
Seyed Salam Kohnepoushi ◽  
Dara Dastan ◽  
Amir Nili-Ahmadabadi

Background: Pistacia atlantica kurdica has recently been shown to possess free radical scavenging ability. The current study aims to investigate the protective effect of this plant against cadmium-induced nephrotoxicity. Methods: Thirty-six rats were divided into 6 groups (6 in each), and treated as follows: group 1 received normal saline (control group), group 2 (positive control) received cadmium by drinking water (100 mg/ L/d), group 3 received 200 mg/kg of P. atlantica extract, and groups 4-6 received cadmium as well as 50, 100 and 200 mg/kg/d of P. atlantica extract (orally), respectively. After 2 weeks, oxidative damage and renal function markers were assayed by standard methods. Results: In cadmium group, a significant increase was observed in serum blood urea nitrogen (BUN) (P<0.01) and lipid peroxidation (LPO) level of renal tissue (P<0.001) and a remarkable decrease was found in total thiol molecules (TTM) of the kidney (P<0.001). Despite the decreased renal antioxidant capacity, these changes were not significant. P. atlantica extract improved the LPO, TTM, and histopathological changes in renal tissue. Conclusion: In this study, although the P. atlantica extract did not have a significant effect on cadmiuminduced renal dysfunction, it did improve the oxidative/antioxidant balance in renal tissue.


2019 ◽  
Vol 1 (4) ◽  
pp. 13-28
Author(s):  
Abdelmonem Awad Hegazy ◽  
Manal Mohammad Morsy ◽  
Rania Said Moawad ◽  
Gehad Mohammad Elsayed

Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.


2020 ◽  
Author(s):  
Hacı Öztürk Şahin ◽  
Mehmet Nuri Duran ◽  
Fatma Sılan ◽  
Ece Sılan ◽  
Duygu Sıddıkoglu ◽  
...  

Abstract Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats. Twenty nine female rats were divided to three groups: Saline control group (Group 1), cisplatin group (Group 2), and cisplatin+melatonin group (Group 3). While the rats in Groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in Group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapited. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-mullerian hormone (AMH) values were measured with enzyme immune-assay technology. Results: While primordial follicles were seen to decrease in Group 2 as compared to Group 1 (p:0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to Group 2 (p:0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p:0.102 and p:0.411, respectively). While TAp63 gene expression significantly increased in Group 2 as compared to control group (p:0.001), we did not detect a statistically significant difference in cisplatin+melatonin group, although gene expression decreased (p:0.34). Conclusion: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage.


2012 ◽  
Vol 5 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Vivek Kumar Dwivedi ◽  
Anuj Bhatanagar ◽  
Manu Chaudhary

ABSTRACT We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid per-oxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.


Author(s):  
Nahed A Hussien ◽  
Hanan R. H. Mohamed

Objective: Cobalt nanoparticles (NPs), especially cobalt oxide NPs (Co3O4 NPs) are attracting unique shaped NPs that are used in different biomedical applications and medicine. Different in vitro studies report their toxic and carcinogenic effect but limited in vivo studies were present on its genotoxic potential. The present study was aimed to evaluate the genotoxic potential of Co3O4 NPs on bone marrow cells and sperms and the protective role of omega-3 in male albino mice.Methods: Animals were segregated into four groups that were orally treated for 3 consecutive days, Group 1: Negative control; Group 2: Omega-3 (250 mg/kg); Group 3: Co3O4 NPs (20 mg/kg); and Group 4: Combined group (250 mg/kg Omega-3 and Co3O4 NPs 20 mg/kg).Results: The present results show that Co3O4 NPs administration significantly increased number of micronucleated polychromatic erythrocytes (PCEs)/1000 PCEs, sperm abnormalities, and DNA damage, significantly decreased sperm motility and concentration in comparison to negative control group. However, Omega-3 administration in the combined group modulates the genotoxic potential of Co3O4 NPs in comparison to Co3O4 NPs group.Conclusion: The present study reports the genotoxic potential of Co3O4 NPs in vivo and assesses the protective role of Omega-3 administration due to its antioxidant effect.


2017 ◽  
Vol 95 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Ola Ahmed El-Gohary ◽  
Mona Abdel-Azeem Said

There are considerable public concerns about the relationship between mobile phone radiation and human health. The present study assesses the effect of electromagnetic field (EMF) emitted from a mobile phone on the immune system in rats and the possible protective role of vitamin D. Rats were randomly divided into six groups: Group I: control group; Group II: received vitamin D (1000 IU/kg/day) orally; Group III: exposed to EMF 1 h/day; Group IV: exposed to EMF 2 h/day; Group V: exposed to EMF 1 h/day and received vitamin D (1000 IU/kg/day); Group VI: exposed to EMF 2 h/day and received vitamin D (1000 IU/kg/day). After 30 days of exposure time, 1 h/day EMF exposure resulted in significant decrease in immunoglobulin levels (IgA, IgE, IgM, and IgG); total leukocyte, lymphocyte, eosinophil and basophil counts; and a significant increase in neutrophil and monocyte counts. These changes were more increased in the group exposed to 2 h/day EMF. Vitamin D supplementation in EMF-exposed rats reversed these results when compared with EMF-exposed groups. In contrast, 7, 14, and 21 days of EMF exposure produced nonsignificant differences in these parameters among all experimental groups. We concluded that exposure to mobile phone radiation compromises the immune system of rats, and vitamin D appears to have a protective effect.


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