scholarly journals Nephroprotective effect of aqueous acetonic extract of Morus alba and its underlying mechanisms against glyphosate-induced toxicity - in vivo model

2021 ◽  
Vol 36 (1) ◽  
pp. 45-59
Author(s):  
Olfa Rebai ◽  
Sami Fattouch ◽  
Mohamed Amri

Glyphosate, the active substance in RoundupR, is the most widely used pesticide in the world and may be present as a residue in derived foods and drinking water. Previous reports have confirmed that extracts from leaves of Morus alba exert many pharmacological activities. However, renoprotective effects of M. alba extract and its underling molecular mechanism is still unknown. Wistar rats (180-200 g) were used in this study (n=5-6). A control group received 0.2 ml normal saline intraperitoneally (i.p) once daily for two weeks. Control animals received standard diet. Treated groups received either polyphenolic extract (100 mg/kg,i.p) or glyphosate (100 mg/kg, i.p), or co-administration (extract ?g ml?1 kg b.w. and glyphosate 100 mg kg?1 b.w, i.p), daily until the 15thday of treatment. Lactate deshydrogenase LDH, serum concentrations of blood urea, creatinine and nitric oxide were measured using standard coloromertic methods. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) and protein carbonyl levels and decline in superoxide dismutase (SOD) activity, was significantly alleviated by mulberry leaves extract (MLE) administration. MLE also appears to be able to modulate altered biochemical parametres by maintaining free iron and Ca2 + homeostasis, and regulate the endogenous antioxidant enzymes system. It seems that concurrent use of the aqueous acetonic fraction of M. alba, rich in chlorogenic acid and its isomeres, can protect kidneys from glyphosate-induced nephrotoxicity. Overall, MLE may possess protective activity against glyphosate-induced toxicity, which may be attributed to chlorogenic acid and its isomers, the most abundant phenolic acids present in its extracts. Mulberry leaves are a source of phenolic compounds and can be a good start towards discovering a new chemical compound which may lead to a new drug. A mulberry extract supplement could serve as a candidate for developing a safe, and promising nutraceutical product for the management of nephrotoxicity.

2019 ◽  
Vol 9 (12) ◽  
pp. 2570 ◽  
Author(s):  
Elena M. Balboa ◽  
Rosendo Millán ◽  
Herminia Domínguez ◽  
Cristina Taboada

Sargassum muticum was processed by hydrothermal extraction under previously optimized non-isothermal conditions (up to 187 °C). The alginate free crude hydrolysate was further concentrated by ultrafiltration, operating in diafiltration mode to produce an extract (SmE) enriched in the fucoidan and the phlorotannin fractions and with low mineral content and antiradical capacity equivalent to that of Trolox. In order to explore the potential of this concentrated product for food or feed additive, the in vivo antioxidant potential was assessed. Male Sprague–Dawley rats were fed SmE dissolved in distilled water at doses of 0.5, 1.0 or 2.0 g kg−1, administered via an intragastric tube daily for three weeks. The weight and organ gain was not significantly affected in the different groups in relation to the control group fed a standard diet. Serum glucose was significantly lowered in the groups receiving the higher SmE doses, liver GPx levels were reduced and liver TBARS levels decreased in rats administered the extract, but no effect on SOD activity in either liver or erythrocytes was observed.


2018 ◽  
Vol 74 (1) ◽  
pp. 54-58
Author(s):  
ANTONINA SOPIŃSKA ◽  
ANNA GROCHOŁA

The purpose of this experiment was to estimate the activity of antioxidant enzymes (SOD, GPx, CAT) in erythrocytes and phagocytes of carps (Cyprinus carpio L.) after intraperitoneal injection of LPS at a dose of 75 μg/100 g b.w. Enzyme activity was determined 3, 6 and 12 hours, as well as 3, 7, 14 and 28 days after LPS administration. After 3 and 6 hours, SOD in erythrocytes increased, respectively, to 188% and 142% of its control group level, and after 12 hours, SOD activity was significantly reduced (117%) and remained unchanged until the end of the experiment. From 12 hours after LPS administration until the end of the study, the PGx level was statistically significantly lower than in the control group, whereas the catalase activity was statistically significantly lower than in the control group in all study periods. In kidney phagocytic cells, SOD activity after 12 hours and 3 days was similar to that in the control group, and in the following study periods it amounted to 66-78% of the control values. Until the 14th day of observation, PGx activity was statistically significantly lower than it was in the control group. Catalase activity in kidney leukocytes was statistically significantly lower than in the control group during the entire experiment, and the lowest in the first study days, amounting to 48-42% of the control group value. The results indicate a long-term decrease in antioxidant enzyme activities in the experimental fish (lasting 14 or 28 days)...


2018 ◽  
Vol 38 (4) ◽  
pp. 434-445 ◽  
Author(s):  
D Rašić ◽  
V Micek ◽  
MS Klarić ◽  
M Peraica

Ochratoxin A (OTA) and citrinin (CTN) commonly coexist in grains. Aiming to evaluate oxidative stress in OTA + CTN toxicity, male Wistar rats were orally treated with two doses of OTA (0.125 and 0.250 mg kg−1 of body weight (b.w.)), CTN (2 mg kg−1 of b.w.) and resveratrol (RSV; 20 mg kg−1 of b.w.) and combined daily during 3 weeks. Protein carbonyl concentrations were measured in kidneys and liver; catalytic activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) level in plasma, kidneys and liver, while malondialdehyde (MDA) concentration was measured in plasma, kidneys, liver and urine. Mycotoxin treatment significantly increased MDA concentration in plasma and kidney and decreased SOD activity in the liver. Rats treated with CTN and OTA125 + CTN had lower plasma GPx activity. Concentration of GSH in the kidney and protein carbonyls in the kidney and liver as well as GPx activity in the kidney and liver, SOD activity in the kidney and CAT activity in the liver were not affected. Protective effect of RSV was observed on GSH in the kidney and plasma and MDA in the kidney, plasma and urine. Oxidative stress is involved in OTA + CTN toxicity in vivo because such treatment affects parameters of oxidative stress, particularly in plasma. RSV can reduce but not overcome oxidative stress induced by combined OTA and CTN treatment.


2014 ◽  
Vol 1025-1026 ◽  
pp. 476-481 ◽  
Author(s):  
Jia Wang ◽  
Rui Wen Yang ◽  
Jing Bo Liu ◽  
Song Yi Lin

The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) are important ones of antioxidant defense systems. Malonaldehyde (MDA) is formed as an end product of lipid peroxidation. Soybean peptides possess antioxidant activity. In previous study, the antioxidant activities of soybean peptides were determinedin vitro. The male ICR mice were intragastrically administered by different molecular weight and dose of soybean antioxidant peptides (SAP) for 60 days. Control group was treated with saline by intragastric administration for 60 days. The SOD, GSH-Px, CAT activity and MDA level were determined in serum. The results suggested the SAP of 1-3k Da had the ability to increase significantly GSH-Px and SOD activity and decrease significantly MDA level at different dose (100 and 200 mg/kg/d) compared with control group (P < 0.05). The SAP of 3-10k Da (200 mg/kg/d) enhanced the GSH-Px activity and decreased significantly MDA level compared with the control group (P < 0.05). The SAP of 10-30k Da (200 mg/kg/d) had the lowest MDA level among all the groups. All the SAP groups and positive control group cannot increase the CAT activity.


Foods ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 170 ◽  
Author(s):  
Wan-Sup Sim ◽  
Sun-Il Choi ◽  
Bong-Yeon Cho ◽  
Seung-Hyun Choi ◽  
Xionggao Han ◽  
...  

The antioxidant and anti-adipogenic activities of a mixture of Nelumbo nucifera L., Morus alba L., and Raphanus sativus were investigated and their anti-obesity activities were established in vitro and in vivo. Among the 26 different mixtures of extraction solvent and mixture ratios, ethanol extract mixture no. 1 (EM01) showed the highest antioxidant (α,α-Diphenyl-β-picrylhydrazyl, total phenolic contents) and anti-adipogenic (Oil-Red O staining) activities. EM01 inhibited lipid accumulation in 3T3-L1 adipocytes compared to quercetin-3-O-glucuronide. Furthermore, body, liver, and adipose tissue weights decreased in the high-fat diet (HFD)-EM01 group compared to in the high-fat diet control group (HFD-CTL). EM01 lowered blood glucose levels elevated by the HFD. Lipid profiles were improved following EM01 treatment. Serum adiponectin significantly increased, while leptin, insulin growth factor-1, non-esterified fatty acid, and glucose significantly decreased in the HFD-EM01 group. Adipogenesis and lipogenesis-related genes were suppressed, while fat oxidation-related genes increased following EM01 administration. Thus, EM01 may be a natural anti-obesity agent.


2021 ◽  
Vol 64 (5) ◽  
pp. 70-75
Author(s):  
Valeriana Pantea ◽  
◽  
Marina Gamaniuc ◽  
Veaceslav Popa ◽  
◽  
...  

Background: Currently, there is a growing interest in new local coordination compounds (CC), which demonstrated antitumor properties, but their influence on the erythrocyte antioxidant system has not been studied. The aim of the study: to study the effects of CC, thiosemicarbazide derivatives –TIA-160, CMT-67 and CMJ-33 on indices of the antioxidant system indicators in erythrocytes peripheral blood in vivo experiments. Material and methods: The action of CC on superoxide dismutase, catalase, total antioxidant capacity was evaluated on a group of 34 white rats, randomly divided into 4 groups: the first control group was injected subcutaneously with saline. The other groups (2 – TIA-160, 3 – CMT-67 and 4 – CMJ-33) were given subcutaneously 3 times a week for 30 days, 0.1µM / kg CC. Results: It was established that the TIA-160 compound demonstrated the highest capacity to induce the expression of erythrocyte catalase that exceeded the control level of 1.8, which did not correlate with the enzymatic superoxide dismutase (SOD) activity. Thus, this study showed that there are differences in the mechanisms of action of thiosemicarbazone derivatives. Conclusions: The influence of tested CC on the indices of the antioxidant system is selective. This selectivity may be the base to their strong selective antiproliferative and cytotoxic action on tumor cells, but not on healthy ones.


2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Hend Maarof Tag ◽  
Ahlem Bargougui ◽  
Sara Gamal Alshayyal ◽  
Amany Kamal ◽  
Hekmat M. Tantawy ◽  
...  

Punica granatum (POM) and Silybum marianum (MT) receiving attention as potential potent anti-oxidant and anti-mutant agents. In this context, the present study was designed to highlight their effects either in vitro as well as in vivo model of induced Hepatocellular carcinoma (HCC). Human hepatoma (HepG2 cells) were treated with MT and POM to explore their antitumor activity then in vivo were carried out on thirty-six male albino rats divided into six groups (n=6). Two weeks after induction of HCC, rats were co-treated with either MT or POM ethanolic extract (500 mg/kg, orally) daily for 8 weeks. The results displayed marked reduction in the viability of HepG2 cells with IC50 equal to 48.4 and 8.6 μg/mL of POM and MT treatment respectively. Considering, in vivo experiment HCC group displayed significant elevation liver function indices (p<0.05). It also elicited depletion of liver reduced glutathione (GSH), and increased content of liver malondialdehyde (MDA) compared to control group. HCC was proved after a significantly elevated alpha-fetoprotein (AFP) level (p<0.05). All of these measurements were diminished significantly after POM and MT treatments, except the GSH level that was increased significantly. Supplementation of pomegranate and milk thistle extracts had a protective effect against chemically induced HCC. 


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1720-1720
Author(s):  
Julia Schüler ◽  
Dagmar Wider ◽  
Dietmar Pfeifer ◽  
Martin Wagner ◽  
Heinz-Herbert Fiebig ◽  
...  

Abstract For a better understanding of myeloma disease and biology, the establishment of reproducible in vivo models is pursued worldwide. We have established a cell linebased, disseminated myeloma model in NOD/SCID-IL2-receptor-gamma-chain−/− (IL2−/−) mice. In the current study, this model was validated in various treatment groups, using 1. bortezomib (0.7mg/kg/day (d); d0, d4, d11), 2. sorafenib (200mg/kg/d; d0–11), 3. dexamethasone (3mg/kg/d, d0–4 + 7–11), in comparison with 4. a control group. L363 cells were injected intratibialy (it) into IL2−/− mice and respective therapies were started 7 days after L363-it-injection (d0). Tumor growth was monitored with daily monitoring of MM symptoms, fluorescence-based in vivo imaging (FI) performed every 2. week and flow-cytometry (FACS; detection of human HLA−A, B, C + CD138) performed once weekly by sacrificing 2 mice per group and analyzing bone marrow (BM), spleen, peripheral blood (PB) and liver. Based on the FACS data, tumor inhibition was calculated as the median percentage of MM cells at respective compartments of the test- vs. control-group multiplied by 100 (optimal test/control (T/C) in %). Furthermore, hollow bones of the injected mice were retrieved when mice were sacrificed for FACS analyses, cells flushed out and MM cells purified by MACS microbeads. Total RNA was isolated from these cells and gene expression profiles will be analyzed using the HG-U133 Plus 2.0 array (Affymetrix) and the Expressionist software (Genedata AG, Basel). L363 engrafted reliably (take rate=100%) at the injection site and in distant organs, such as BM (100%), spleen (38%) and rarely liver (8%). Control mice developed MM symptoms, such as hind limb pareses, weight loss and osteolyses. L363 cells were detected by FACS and FI, not only at injection sites, but also in the BM, hollow bones and spleen. Primary tumor development was markedly reduced by sorafenib (optimal T/C of 23% on d14), as well as with dexamethasone and bortezomib, albeit to a much lesser extend (optimal T/C: 81% + 62% on d14, respectively). BM metastases were also significantly reduced by sorafenib with an optimal T/C value of 67% on d28. Dexamethasone and bortezomib, the latter possibly due to subclinical doses (determined after titration and toxicity experiments), had no relevant influence on BM metastases suppression (97% + 100% optimal T/C on d28, respectively). Thus, L363 engraftment into IL2−/− is a valuable in vivo model for MM which exhibits high reproducibility, take- and metastases-rates and closely mimics the clinical situation. Collection of whole-body FI data proved to be a time- and animal-saving analysis that allows to closely monitor MM growth. Further investigations will validate the very promising antitumor activity of sorafenib and evaluate the potentially synergistic effect of bortezomib and sorafenib. Amongst others, a detailed characterization of the antitumor activity of both compounds will be provided by the gene expression profile of L363 cells isolated from untreated as well as treated mice. The evaluation of new therapeutic approaches in comparison to standard agents was thus successfully conducted, suggesting that our model serves as a valuable tool in the development of new anticancer strategies.


1997 ◽  
Vol 86 (6) ◽  
pp. 998-1006 ◽  
Author(s):  
Paul D. Sawin ◽  
Vincent C. Traynelis ◽  
Gretchen Rich ◽  
Bruce A. Smith ◽  
Timothy J. Maves ◽  
...  

✓ The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis remains obscure. Radiographic studies suggest that chymopapain does not alter disc fragment size acutely; nonetheless, patients often report symptom resolution within a few days, even hours, of treatment. The authors postulate that, in addition to its chemonucleolytic action, chymopapain may possess antiinflammatory properties. To test this hypothesis, the authors assessed the ability of chymopapain to modulate the activity of the proinflammatory enzyme phospholipase A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory neuropathy in an in vivo model of sciatica. Thirty-nine male Fischer rats were randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone, or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation with loose chromic gut suture to induce inflammatory mononeuropathy. The animals were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7 (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On Day 7, three animals from each group were killed to assess PLA2 activity prior to treatment. The remainder were given a single infusion of saline, betamethasone (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14, the remaining animals were killed and their sciatic nerves were removed. The tissue was homogenized and the PLA2 activity was determined using [14C]arachidonate—labeled Escherichia coli phospholipid membrane as a substrate. Lipids were extracted and separated by thin-layer chromatography. All animals developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72 hours postoperatively; these included gait disturbance, flexion deformity, and hyperalgesia of the involved hindlimb. The degree of mechanical and thermal hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the betamethasone- and chymopapain-treated groups than in the saline-treated controls (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs. betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day 0) was 11.6 ± 4.9 nmol phospholipid hydrolyzed per minute per milligram of protein. The PLA2 activity at Day 7 was 74.4 ± 18.2 (ligated side) and 21.2 ± 11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain- (47.8 ± 12.3) and betamethasone- (39.7 ± 9.5) treated groups compared with the saline control group (62.3 ± 11.2), (saline- vs. chymopapain-treated groups p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity in nonligated specimens was 18.6 ± 10.1. These data indicate that chymopapain exhibits antiinflammatory properties in vivo, reducing PLA2 activity and ameliorating mechanical hyperalgesia in this model of inflammatory sciatic neuropathy.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3677
Author(s):  
João C. Fernandes ◽  
Elizângela G. Schemitt ◽  
Juliana Da Silva ◽  
Norma P. Marroni ◽  
Ana Lima ◽  
...  

Stilbenes are a major grapevine class of phenolic compounds, known for their biological activities, including anti-inflammatory and antioxidant, but never studied in combination. We aimed to evaluate the effect of trans-resveratrol + ε-viniferin as an antioxidant mixture and its role in inflammatory development an in vivo model of severe acute liver failure induced with TAA. Trans-resveratrol + trans-ε-viniferin (5 mg/kg each) was administered to Wistar rats. Resveratrol + ε-viniferin significantly decreased TBARS and SOD activity and restored CAT and GST activities in the treated group. This stilbene combination reduced the expression of TNFα, iNOS, and COX-2, and inhibited MMP-9. The combination of resveratrol + ε-viniferin had a hepatoprotective effect, reducing DNA damage, exhibiting a protective role on the antioxidant pathway by altering SOD, CAT, and GST activities; by downregulating TNFα, COX-2, and iNOS; and upregulating IL-10. Our results suggested that adding viniferin to resveratrol may be more effective in hepatoprotection than resveratrol alone, opening a new perspective on using this stilbene combination in functional diets.


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