scholarly journals Antioxidant Protection against Pathological Mycotoxins Alterations on Proximal Tubules in Rat Kidney

2011 ◽  
Vol 1 (4) ◽  
pp. 118 ◽  
Author(s):  
Awatef Ali ◽  
Susan Abdu

Background: Ochratoxin A (OTA) was one of the mycotoxins and received attention worldwide because of the hazard it posed to human and animal health, where the kidney was the primary target organ for OTA toxicity. In the other hand, dates served as a good source of natural antioxidants and could potentially be considered as a functional food.Methods: The study was performed in the department of biology in King Abdulaziz University. Animals were gavage administrated and divided into four groups: first group received (sodium bicarbonate), second group received (289 µg OTA /kg B.W. /day), third group received (1mg Ajwa/kg B.W. / day) and fourth group received (289 µg OTA /kg B.W./day+ 1mg Ajwa /kg B.W. / day). Serum (creatinine - urea) levels were measured in each group at the time of tissue collection, some biopsies were fixed in 10% buffered formalin solution for light microscopy processing stained with Haematoxylin and Eosin (H& E.), Periodic Acid-Schiff (PAS) and Masson´s Trichrome (M.T.).Other biopsies were immediately collected into electron microscopy processing. Results: After 28 days, a significant decrease in body weight, kidney weight and relative weight was detected in OTA treated group. Also, Serum (creatinine-urea) level were elevated. The normal cyto-architecture of proximal tubules were lost exhibiting damaged bruch border, degenerated, binucleated and karyomegalic cells. The most destructed ultra-structure was the mitochondria which severely swollen with disintegrated membranes. In Ajwa Date extract-group the proximal tubules were normal, whereas in Ajwa date extract + OTA -group the severity of the lesions was significantly reduced. Conclusion: The present results indicated that, Ajwa date have protective effects and ameliorated the lesions of Ochratoxin nepherotoxicity which might lead to kidney failure. Key words: Ochratoxin A., Ajwa date, proximal tubules, light –structure, ultra –structure, biochemical analysis, morphometry.

2014 ◽  
Vol 307 (4) ◽  
pp. F388-F395 ◽  
Author(s):  
Ying Liu ◽  
Zhanjun Jia ◽  
Ying Sun ◽  
Li Zhou ◽  
Maicy Downton ◽  
...  

Cyclooxygenase 2 (COX-2) has an established role in postnatal kidney development. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is recently identified as an endogenous inhibitor of COX-2, limiting the production of COX-2-derived prostanoids in several pathological conditions. The present study was undertaken to examine the regulation of renal 15-PGDH expression during postnatal kidney development in rats compared with COX-2. qRT-PCR and immunoblotting demonstrated that 15-PGDH mRNA and protein in the kidney were present in neonates, peaked in the second postnatal week, and then declined sharply to very low level in adulthood. Immunostaining demonstrated that at the second postnatal week, renal 15-PGDH protein was predominantly found in the proximal tubules stained positive for Na/H exchanger 3 and brush borders (periodic acid-Schiff), whereas COX-2 protein was restricted to macular densa and adjacent thick ascending limbs. Interestingly, in the fourth postnatal week, 15-PGDH protein was redistributed to thick ascending limbs stained positive for the Na-K-2Cl cotransporter. After 6 wk of age, 15-PGDH protein was found in the granules in subsets of the proximal tubules. Overall, these results support a possibility that 15-PGDH may regulate postnatal kidney development through interaction with COX-2.


1981 ◽  
Vol 241 (4) ◽  
pp. F403-F411 ◽  
Author(s):  
P. Vinay ◽  
A. Gougoux ◽  
G. Lemieux

A suspension of cortical tissue fragments prepared by collagenase digestion of renal cortex obtained from fed and chronically acidotic (NH4Cl) rats was separated into four bands on a Percoll density gradient. By microscopic examination, vital staining with trypan blue, and histologic staining technique (periodic acid-Schiff) the F4 band was shown to contain only (greater than 98%) proximal tubules, whereas the F1 band was significantly enriched (70%) with distal tubules contaminated by glomeruli and short segments of proximal tubules. Intra/extracellular ratios for PAH of 15 were measured in the F4 band and of 2 in F1 band. ATP was 1.4 and 2.8 mumol/g in the F4 and F1 bands, respectively, and was stable for at least 60 min. The proximal F4 band was shown to be gluconeogenic (L-glutamine or L-lactate 2.5 mM as substrate) and to adapt to metabolic acidosis. The distal F1 band was shown to be glycolytic (glucose 2.5 mM) with no changes with acid-base status. All fractions were shown to metabolize glutamine, but the metabolic fate of this amino acid was different in proximal and distal structures. A F4/F1 activity ratio for the proximal cytoplasmic phosphoenolpyruvate carboxykinase enzyme of 2.6 and 4.3 was observed in normal and acidotic rats, respectively. In contrast, a F4/F1 ratio of 0.13 and 0.22 was observed for the distal cytoplasmic hexokinase enzyme. This preparation, therefore, allows the metabolism of a homogeneous population of proximal tubular fragments to be studied and can be used to obtain information on enzyme location within the nephron.


2021 ◽  
pp. 1-14
Author(s):  
S.D. Stoev ◽  
K. Dimitrov ◽  
I. Zarkov ◽  
T. Mircheva ◽  
D. Zapryanova ◽  
...  

A protective effect of two herbs, Glycyrrhiza glabra and Tinospora cordifolia, given as feed additives was observed against the growth inhibitory effect of ochratoxin A (OTA) and associated immunosuppression and biochemical or pathomorphological changes. The feed levels of 3 mg/kg OTA and fine powder of one of both herbs were given during a period of 32 days to female broiler chicks divided into 3 experimental and 1 control groups (14 chicks per group). The observed pathological and biochemical changes, the changes in relative organs’ weight and body weight, and the decrease of antibody titer against Newcastle disease were more pronounced in the OTA-treated chicks without herbal supplementation, and less pronounced in the chicks treated additionally with G. glabra or T. cordifolia as was shown by the better feed performance and the higher body weight in the chicks treated with the herbs. The higher relative weight of lymphoid organs of the chicks supplemented with both herbs revealed their beneficial effects on the immune system. The hepatoprotective effect of both herbs was evident, being stronger in the chicks additionally supplemented with G. glabra shown by the pathomorphological findings and by the lower levels of aspartate transaminase (131.1 U/l) compared to chicks given only OTA (156.0 U/l). A protective effect of T. cordifolia on the bone marrow and kidneys was found as was shown by the lower levels of uric acid (382.9 μmol/l) compared to chicks given only OTA (466.9 μmol/l).


1972 ◽  
Vol 50 (3) ◽  
pp. 292-298
Author(s):  
V. N. Katiyar ◽  
B. L. Dinh

The incorporation of 14C-leucine into the microsomal proteins of nephrotic rat kidney was much higher than that in the microsomal proteins of the normal rat kidney. When the newly synthesized microsomal proteins were analyzed by acrylamide gel electrophoresis, it was found that the higher incorporation of 14C-leucine in nephrotic rat kidney was mostly due to an increase in the biosynthesis of a tissue protein which migrated in the electrophoretic zone between serum albumin and transferrin. This protein did not react with rabbit antiserum to normal rat serum and was stained with periodic acid – Schiff reagent. It was believed to be excreted in the urine of nephrotic rats in great quantity and was easily identified as a distinct band in electrophoregrams of urine from these rats.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Raphaelle Corremans ◽  
Benjamin Vervaet ◽  
Patrick D'Haese ◽  
Anja Verhulst

Abstract Background and Aims Metformin, a biguanide drug, is the first-line oral antidiabetic agent used by 200 million patients suffering from type 2 diabetes mellitus. In the last decades, it has become clear that metformin exerts benign pleiotropic actions beyond its prescribed use and emerging data show protective effects against different age-related diseases. Additionally, recent preclinical and clinical data point towards a beneficial impact of metformin on the kidney. Current treatment strategies for chronic kidney disease (CKD) mainly focus on controlling important risk factors, such as high blood pressure and diabetes. To date, effective treatment directly targeting the kidney is lacking. Here, the ability of metformin to attenuate progression of already established CKD, independent from its effects on diabetes, was investigated. Method A rat model of adenine-induced CKD (n=64) was used. Metformin (200 mg/kg) or vehicle (1% carboxymethylcellulose) treatment, by daily oral gavage (7 days/week), was initiated after 4 and 5 weeks of adenine (0.25%) administration; i.e. after CKD had developed. Treatment was continued during 4 weeks until the end of the study (i.e. week 8 and 9, respectively). A constant dose volume of 10 mL/kg was used. The effect of metformin on renal function and histopathology was studied. Results Serum creatinine levels dramatically rose in vehicle-treated CKD rats: from 0.6 ± 0.1 mg/dL (week 0) to 1.3 ± 0.2 mg/dL (week 4) and 2.6 ± 1.2 mg/dL (week 5) and further to 5.7 ± 0.6 mg/dL (week 8) and 4.8 ± 1.1 mg/dL (week 9). Metformin treatment, which started after 4 and 5 weeks, prevented almost completely further increases in serum creatinine levels after 8 (2.0 ± 0.5 mg/dL) and 9 (2.9 ± 0.5 mg/dL) weeks compared to vehicle-treated CKD rats (p<0.05). The calculation of creatinine clearance confirmed these results. Histological examination of periodic acid–Schiff (PAS)-stained renal sections revealed less tubular dilation, epithelial flattening, brush border loss and, basement membrane thickening in metformin-treated CKD rats in comparison to vehicle-treated animals. The renal tubulointerstitial area percentage was significantly lower in metformin-treated CKD rats, as compared to vehicle treatment (from 35% and 41% tubulointerstitial area after 4 and 5 weeks, respectively, to 50% and 53% in vehicle-treated CKD rats and 34% and 41% in metformin-treated CKD rats after 8 and 9 weeks, respectively). Leukocyte common antigen (CD45)-staining revealed significantly less infiltration of inflammatory cells in metformin-treated CKD rats after 9 weeks (8%) as compared to the vehicle-treated CKD rats (12%). Semiquantitation of proliferating cell nuclear antigen (PCNA)-staining at 9 weeks showed that the amount of tubules containing more than 50% proliferating cells were increased, whereas PCNA-negative tubules were decreased in metformin-treated CKD rats compared to vehicle-treated CKD rats (p<0.05) . Conclusion Therapeutic metformin treatment is able to attenuate the progression of pre-existing adenine-induced CKD in rats.


2019 ◽  
Vol 12 (3) ◽  
pp. 257-268 ◽  
Author(s):  
S.D. Stoev ◽  
P. Njobeh ◽  
I. Zarkov ◽  
T. Mircheva ◽  
D. Zapryanova ◽  
...  

The protective effects of herbal feed additives Silybum marianum, Withania somnifera and Centella asiatica against the toxic effects of ochratoxin A (OTA) were studied in 70 broiler chicks aged from 11 to 42 days. OTA was given with the feed at levels 5 mg/kg, whereas S. marianum, W. somnifera and C. asiatica were given at levels of 1,100, 4,000 and 4,600 mg/kg, respectively. All chicks were immunised at the age of 14 days against Newcastle disease. A protective effect of all studied herbal additives against the immunosuppressive effect of OTA and associated biochemical or pathomorphological changes was seen. The intensity of macroscopical and histopathological changes, the deviations in relative organs’ weight or body weight, the biochemical changes and the decrease of antibody titer were strongest in the OTA-exposed chicks without herbal supplementation; followed by chicks treated additionally with C. asiatica, whereas the same changes were significantly slighter or not seen in chicks additionally treated with the herbal additives W. somnifera or S. marianum. The slight increase in the serum levels of uric acid and the enzyme activity of aspartate transaminase and alanine transaminase also supported the protective effects of both herbs on the kidneys and/or liver. The strong immunosuppressive effect of OTA on humoral immune response against Newcastle disease was completely prevented in the chicks taking the herbal additives W. somnifera or S. marianum, which was supported by the higher relative weight of immunocompetent (lymphoid) organs in the same chicks. A hepatoprotective effect was found in OTA-exposed chicks treated additionally with W. somnifera and S. marianum, whereas a nephroprotective effect was only found in the chicks additionally treated with S. marianum as observed from the biochemical and pathomorphological findings. The same herbs could be used as a practical approach for safely utilising of OTA-contaminated feed.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Soojin Park ◽  
Sung-Hwa Sohn ◽  
Kyung-Hwa Jung ◽  
Kun-young Lee ◽  
Yu Rim Yeom ◽  
...  

Maekmoondong-tang (MMDT) has long been used in Asian countries to treat respiratory diseases. However, the precise mechanisms underlying its effects on asthma are unknown. This study was conducted to evaluate the protective effects of MMDT in a cockroach allergen (CKA-)induced animal model of allergic asthma. After being challenged with CKA, the number of macrophages, eosinophils, neutrophils, lymphocytes, and total cells in the bronchoalveolar lavage fluid (BALF) was evaluated. The Th2 specific cytokines IL-4, IL-5, and IL-13 were also analyzed in BALF along with IgE levels in serum. For histological analysis, hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and immunohistochemical staining were performed. In addition, airway hyperresponsiveness was assessed by noninvasive plethysmography. The cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the MMDT-treated groups compared with the cockroach extract-injected (CKA) groups. In addition, the IgE, IL-4, IL-5, and IL-13 levels were significantly decreased in the MMDT group. MMDT treatment also significantly attenuated airway hyperresponsiveness. These results demonstrated that MMDT significantly reduced the hallmark signs of asthma: elevated serum IgE, airway eosinophilia, airway remodeling, mucus hypersecretion, and airway hyperresponsiveness. The remarkable antiasthmatic effects of MMDT suggest its therapeutic potential in allergic asthma treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Yijun Zhou ◽  
Chaojun Qi ◽  
Shu Li ◽  
Xinghua Shao ◽  
Zhaohui Ni

Background/Aims. Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Calcium dobesilate (CaD) is widely used to treat diabetic retinopathy. Recent studies have demonstrated that CaD exerts protective effects against diabetic nephropathy. The aim of this study was to elucidate the molecular and cellular mechanisms underlying the protective effects of CaD. Methods. Human umbilical vein endothelial cells (HUVECs) were cultured with different D-glucose concentrations to determine the effects of high glucose on HUVEC gene expression. HUVECs were also incubated with CaD (25 μM, 50 μM, and 100 μM) for 3 days to determine the effects of CaD on HUVEC viability. db/db mice were treated with CaD. 2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) blocked the nuclear factor-κB (NF-κB) pathway in HUVECs. A pentraxin 3 (PTX3) small interfering RNA (siRNA) intervention experiment was performed in the cells. An adenovirus-encapsulated PTX3 siRNA intervention experiment was performed in db/db mice. Western blot and real-time PCR analyses were used to detect PTX3, p-IKBa/IKBa (I-kappa-B-alpha), and p-eNOS/eNOS (endothelial nitric oxide synthase) expression in mice and HUVECs. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining were used to observe renal tissue damage in mice. PTX3 expression was observed by immunohistochemical staining. Results. CaD downregulated the expression of PTX3 and p-IKBa/IKBa and upregulated the expression of p-eNOS/eNOS in vitro. When TPCA-1 was used, high glucose induced high PTX3 expression, and the expression of p-eNOS/eNOS increased. After PTX3 gene silencing, the expression of p-eNOS/eNOS also increased. In vivo, CaD reduced the expression of PTX3 and p-IKBa/IKBa in the kidneys of db/db mice and increased the expression of p-eNOS/eNOS. After PTX3 gene silencing, the urine protein and renal function of db/db mice were ameliorated, the glomerular extracellular matrix was decreased, and the expression of p-eNOS/eNOS was increased. Conclusions. Our results suggested that CaD may inhibit the expression of PTX3 by altering the IKK/IKB/NF-κB pathway, thereby improving endothelial dysfunction in HUVECs. PTX3 may be a potential therapeutic target for DKD.


1999 ◽  
Vol 277 (3) ◽  
pp. F404-F412 ◽  
Author(s):  
Mark D. Okusa ◽  
Joel Linden ◽  
Timothy Macdonald ◽  
Liping Huang

A2A adenosine receptors (A2A-ARs) are known modulators of renal hemodynamics and potent inhibitors of inflammation. We sought to determine whether selective activation of A2A-ARs protects kidneys from ischemia-reperfusion injury. The ester derivative of DWH-146 (DWH-146e), a selective A2A agonist, was found to be more potent and selective for A2A-ARs than the prototype compound CGS-21680. Osmotic minipumps were implanted subcutaneously to infuse into rats either vehicle or DWH-146e (0.004 μg ⋅ kg−1 ⋅ min−1), during and after ischemia-reperfusion injury. Following 24 and 48 h of reperfusion, the rise in serum creatinine and blood urea nitrogen for vehicle-treated rats was substantially elevated compared with DWH-146e-treated rats. Histological examination revealed widespread tubular epithelial necrosis and vascular congestion in the outer medulla of vehicle-treated compared with DWH-146e-treated animals. ZM-241385, a selective A2A antagonist, blocked the protective effect of DWH-146e. Delaying administration of DWH-146e until the initiation of reperfusion also decreased serum creatinine. We conclude that 1) selective A2A-AR activation by DWH-146e reduces ischemia-reperfusion injury in rat kidneys, 2) the effect of DWH-146e is A2A receptor mediated, and 3) the protective effects are mediated by preventing injury during the reperfusion period.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shu Fu ◽  
Jiamei Chen ◽  
Chen Zhang ◽  
Jinfeng Shi ◽  
Xin Nie ◽  
...  

Although Periplaneta americana L. and its modern preparation, Kangfuxin liquid, have been extensively applied for ulcerative diseases in gastrointestinal tract (e.g., gastric ulcer (GU) and ulcerative colitis, the effective components and potential mechanisms) remain unclear. In accordance with the accumulating research evidences, the relieving/exacerbating of GU is noticeably correlated to focal tissue programmed cell death. Herein, gastro-protective effects of the effective Periplaneta americana L. extract (PAE) fraction were assessed in vitro and in vivo, involving in programmed cell death-related signaling channels. To screen the effective PAE fraction exerting gastroprotective effects, several PAE fractions were gained based on a wide range of ethanol solution concentration, and they were assessed on ethanol-induced ulcer mice. Based on HPLC investigation with the use of nucleosides, the chemical composition of screened effective PAE, extracted by 20% ethanol, was analyzed in terms of quality control. Based on CCK-8 assay, the protective effects on GES-1 cells, impaired by ethanol, of PAE were assessed. After 3 days pre-treatment with PAE (200, 400, 800 mg/kg), the gastric lesions were assessed by tissue morphology, and periodic acid-schiff (PAS) staining, as well as hematoxylin and eosin (H&E) based histopathology-related investigation. The levels for inflammation cytokines (IL1-β, TNF-α, IL-18, PGE2, and IL-6), antioxidant indices (SOD and MDA) were examined via ELISA. In the meantime, based on Western Blotting assay, the expression levels of some programmed cell death-related protein targets (NLRP3, caspase-1, NF-κB p65, MyD88, and TLR4) were analyzed. As revealed from the results, PAE is capable of alleviating gastric mucosa impairment, suppressing the inflammatory cytokines, and down-regulating the MyD88/NF-κB channels. Accordingly, 20% ethanol extract of Periplaneta americana L. would contribute its gastroprotective effects, thereby providing the evidence that its anti-GU mechanisms correlated with inhibiting programmed cell death channel.


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