scholarly journals Orientin Attenuates Cisplatin-Induced Renal Toxicity by Reducing Oxidative Stress and Inflammation

2021 ◽  
Vol 41 (04) ◽  
pp. 574-578
Author(s):  
Muhammad Umar Ijaz

Cisplatin (CP), an effective chemotherapeutic drug, has been widely used to treat the several types of tumors. Orientin (ORI) is a flavonoid that shows versatile therapeutic activities. The current research was planned to observe the protective role ORI on CP induced renal injury in rats. Twenty-four male rats were divided into four groups equally and termed as control, CP (10 mg/kg), CP (10 mg/kg) + ORI (40 mg/kg) and ORI (40 mg/kg). After seven days trial, rats were dissected and different parameters were analyzed. Results indicated that the CP administration significantly reduced the activities of catalase, peroxidase, glutathione reductase and glutathione content whereas it increased the level of hydrogen peroxide and TBARS (thiobarbituric acid reactive substances). CP increased the creatinine and urea levels while decreased the creatinine clearance. Moreover, CP significantly increased the inflammatory markers, including nuclear factor kappa-B, tumor necrosis factor-α, Interleukin-6, Interleukin-1β levels, cyclooxygenase-2 activity and histopathological damages. However, co-administration of ORI displayed curative effects against CP-induced renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the ORI is a potential bioflavonoid that can potentially counter the CP-induced renal damage.

2018 ◽  
Vol 96 (4) ◽  
pp. 319-327 ◽  
Author(s):  
Onur M. Yaman ◽  
Hayriye Erman ◽  
Ibrahim Guner ◽  
Olgu Enis Tok ◽  
Mukaddes Pala ◽  
...  

Aortic cross-clamping-induced ischemia–reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.


2015 ◽  
Vol 58 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Miroslav Pohanka ◽  
Branislav Ruttkay-Nedecký ◽  
Josef Fusek ◽  
Vojtěch Adam ◽  
René Kizek

Melatonin is a hormone with strong antioxidant properties. In this experiment, Freund’s complete adjuvant was used as a stressogenic substance given to laboratory outbred mice, whereas melatonin was investigated as a protectant against the stressogenic effect. Levels of low molecular weight antioxidants, thiobarbituric acid reactive substances, and tumor necrosis factor α and activity of glutathione reductase were determined in blood from the animals. Surprisingly, melatonin was not involved in direct regulation of antioxidants, thiobarbituric acid reactive substances and tumor necrosis factor α. On the other hand, melatonin regulated glutathione reductase activity. We can conclude on regulation of metabolism caused by melatonin in the model. The effect was more important than the expected regulation of immunity and basal oxidative homeostasis.


2020 ◽  
Author(s):  
Chih-Chao Chiang ◽  
Yi‐Rong Li ◽  
Kuei-Hung Lai ◽  
Wei-Jen Cheng ◽  
Shih-Chao Lin ◽  
...  

Abstract Abstract: Background: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, are not elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. Methods: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund’s adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. Results: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1β, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. Conclusions: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.


2021 ◽  
pp. 096032712199190
Author(s):  
AA Dar ◽  
A Fehaid ◽  
S Alkhatani ◽  
S Alarifi ◽  
WS Alqahtani ◽  
...  

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1β) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Shun-Guang Wei ◽  
Yang Yu ◽  
Robert B Felder

Introduction: Accumulating evidence indicates that sex differences exist in the clinical and experimental outcomes of various cardiovascular diseases. In addition to its protective effect on renin-angiotensin system activity, estrogen has an anti-inflammatory influence. The central actions of pro-inflammatory cytokines (PICs) contribute significantly to cardiovascular and autonomic dysfunction in hypertension and heart failure. In male adult rat, central administration of PICs induces substantial increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA), and blocking PICs reduces sympathetic excitation in experimental models of hypertension and heart failure. Whether PICs have similar central sympatho-excitatory effects in the female rat remains unknown. Hypothesis: We hypothesized that female rats may be protected from the central cardiovascular and autonomic effects of PICs. Methods: Urethane anesthetized male and female Sprague Dawley rats (10-12 weeks) underwent an intracerebrovascular (ICV) injection of the prototypical PIC tumor necrosis factor-α (TNF-α, 100 ng). BP (mmHg), HR (beats/min) and RSNA (% change) responses were continuously recorded for 4-5 hours. Results: In male rats (n=6), ICV TNF-α induced a dramatic and long-lasting increase (*p<0.001 vs. baseline) in BP (23.1 ± 2.5*), HR (82 ± 8*) and RSNA (109.5 ± 4.3 %*), that began within 20-30 mins and peaked at 90-120 mins after ICV injection. In the female rats (n=6), ICV TNF-α elicited significantly (p<0.05) smaller increases (*p<0.001 vs. baseline) in BP (14.8 ± 1.8*), HR (55 ± 6*) and RSNA (78.5 ± 6.3*), compared with the male rats. Conclusion: These data demonstrate a sex difference in the cardiovascular and sympathetic responses to centrally administered PICs. Whether the observed differences can be explained by an estrogen effect on TNF-α signaling per se or by an estrogen effect on TNF-α-induced renin-angiotensin activity remains to be determined. However, a reduced response of female rats to central inflammation may be an important contributor to sex differences in pathophysiology of hypertension and heart failure.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Debasis De ◽  
Kausik Chatterjee ◽  
Kazi Monjur Ali ◽  
Tushar Kanti Bera ◽  
Debidas Ghosh

Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous-methanolic (2 : 3) extract ofSwietenia mahagoni(L.) Jacq. (family Meliaceae) seed studied in streptozotocin-induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilledwater−1100 gm b.w.−1rat−1 day−1) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract ofS. mahagoniseed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes.


2012 ◽  
Vol 48 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Thaís Maria da Fonseca Pletiskaitz ◽  
Guiomar Nascimento Gomes

This study investigated the beneficial effects of D-α-tocopherol supplementation in protecting against the renal morphological and functional changes caused by hypertension. Spontaneously hypertensive (SHR) and normotensive control (WKY) rats received D-α-tocopherol (80 mg/kg by gavage) or vehicle (mineral oil) every other day for 60 days, from the age of 2 months. After this treatment period, all animals were assessed for renal morphological and functional parameters. The glomerular hypertrophy, increased interlobular wall thickness and enlarged renal vascular resistance found in SHR were reduced by D-α-tocopherol treatment. Sodium and volume retention observed in SHR were also decreased by D-α-tocopherol treatment. Moreover, D-α-tocopherol supplementation significantly reduced arterial pressure in SHR but not in WKY. D-α-tocopherol also reduced the excretion of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, in SHR. These results suggest that D-α-tocopherol supplementation can reduce kidney damage induced by hypertension.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Neelam Chandra ◽  
Nalini Pandey

Black gram (Vigna mungo L. var. DPU-88-31), an edible legume, was grown at 1, 2, 4, 6, and 8 meq S L−1 to study the effect of deficient and excess level of sulfur on oxidative metabolism. Plants supplied by 4 meq S L−1 showed optimum yield. Sulfur deficient plants (1 and 2 meq S L−1) showed reduction in growth and chlorosis of young leaves. Tissue sulfur and cysteine concentration was increased with increasing sulfur supply. The thresholds for critical concentration of sulfur deficiency and toxicity were 0.315% and 0.434% dry weight. Biomass and photoassimilatory pigments were decreased and carbohydrates (sugar and starch) were accumulated in leaves of sulfur deficient and excess plants. Accumulation of hydrogen peroxide and thiobarbituric acid reactive substances in sulfur deficient and excess plants caused oxidative damage in plants which was also evident by the increase in the activity of superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, glutathione reductase, and concentration of ascorbate and nonprotein thiols.


2018 ◽  
Vol 4 (4) ◽  

Objective Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are stillvery limited. Various theories have been suggested regarding the pathophysiology of acute pancreatitis, lot of research into differentmedical treatments for the treatment of acute pancreatitis, but it is not clear what benefits each treatment has, or indeed if any medicaltreatment is beneficial apart from supportive treatment.Aim To clarify the potential therapeutic effect of octreotide, trimetazidine, and their combination in acute pancreatitis.Methods Acute pancreatitis was induced by L-arginine and treated with octreotide subcutaneously, trimetazidine intraperitoneally andcombination therapy by octreotide and trimetazidine. The rats were followed for 24 h. At the 24th hour we determined serum levels oftumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total antioxidant capacity (TAC), lipase, and amylase, and the pancreatic tissues wereanalyzed histopathologically.Results TNF-α (P < 0.001), IL-1β (P < 0.001), TAC (P < 0.001), lipase (P < 0.001), and amylase (P < 0.001) serum levels and scores ofhistopathological changes (P < 0.05) were significantly lower in combination group as compared with both octreotide and trimetazidinegroups.Conclusion Combination treatment markedly decreases biochemical and histopathological changes in acute pancreatitis, thus amelioratepancreatic injury in l-arginine induced acute pancreatitis.


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