Renoprotective Effect of Fucoidan from Seaweed Sargassum angustifolium C. Agardh 1820 on Gentamicin-Induced Nephrotoxicity: From Marine Resources to Therapeutic Uses

Background: Nephrotoxicity is a major side effect of aminoglycoside antibiotics, caused by oxidative damage and inflammation. Fucoidan, a group of sulfated polysaccharides derived from different species of brown algae, are well recognized for their antioxidant and anti-inflammatory activities. Objectives: In the present study, we aimed to investigate, for the first time, the efficacy of fucoidan extracted from Sargassum angustifolium C. Agardh 1820 against gentamicin-induced nephrotoxicity in rats. Methods: Twenty-eight male Wistar rats were divided into 4 groups of control, gentamicin (100 mg/kg), and gentamicin plus 50- and 100-mg/kg/day fucoidan pretreatment. In the end, all rats were killed, and then urine, blood, and tissue samples were prepared. Kidney weight (KW), body weight (BW), and 24-hour urine volume, as well as serum creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, were measured. Kidney samples were also evaluated for histopathological changes. Results: Gentamicin significantly increased KW, KW/BW ratio, 24-hour urine volume, serum Cr, MDA, and BUN levels; however, fucoidan pretreatment, especially at a dose of 50 mg/kg, significantly returned these variables near to the control group values. Gentamicin also decreased BW gain, Cr clearance, SOD activity, and the degree of renal tissue damage compared to the control group, while treatment with fucoidan significantly reversed these alterations. Conclusions: The results show that fucoidan from S. angustifolium C. Agardh 1820 ameliorates gentamicin-induced nephrotoxicity by alleviating oxidative stress and augmenting antioxidant enzymes activity in renal tissue, suggesting the potential use of this fucoidan in a clinical setting.

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Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity

Current Molecular Pharmacology ◽

10.2174/1874467213666200220142202 ◽

2020 ◽

Vol 13 (4) ◽

pp. 342-352 ◽

Cited By ~ 1

Author(s):

Vipin K. Verma ◽

Salma Malik ◽

Ekta Mutneja ◽

Anil K. Sahu ◽

Kumari Rupashi ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Tissue ◽

Isoquinoline Alkaloid ◽

Experimental Models ◽

Beclin 1 ◽

Control Treatment ◽

Control Group ◽

Treatment Groups ◽

Single Intraperitoneal Injection ◽

Male Wistar Rats

Background: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. Aim: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. Methods: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters. Results: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. Conclusion: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.

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POTENTIAL DIURETIC EFFECT OF CURCUMA AMADA ROXB. RHIZOME EXTRACTS

INDIAN DRUGS ◽

10.53879/id.50.04.p0034 ◽

2013 ◽

Vol 50 (04) ◽

pp. 34-38

Author(s):

P Bommannavar ◽

◽

K. Patil

Keyword(s):

Aqueous Extract ◽

Urine Volume ◽

Control Group ◽

Aqueous Extracts ◽

Diuretic Activity ◽

Curcuma Amada ◽

Male Wistar Rats ◽

Total Urine ◽

Dose Dependent Increase ◽

Dose Dependent

The present study was undertaken to establish the diuretic activity of alcoholic and aqueous extract of dried rhizomes of Curcuma amada Roxb in rats. Alcoholic and aqueous extracts of rhizomes were administered to experimental male Wistar rats orally at doses of 250 and 500 mg/kg and compared with furosemide (10 mg/kg) as the reference standard. The parameters measured for diuretic activity were total urine volume, urine electrolyte concentration such as sodium, potassium and chloride have been evaluated. The rats treated with alcoholic and aqueous extract of Curcuma amada in a dose of 250 and 500 mg/kg showed higher urine output when compared to the respective control. Both alcoholic and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. The result indicates that alcoholic and aqueous extract is an effective natriuretic and kaliuretic diuretic, which supports the traditional claim about the Curcuma amada Roxb being used as diuretics.

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A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

Physiological Research ◽

10.33549/physiolres.932738 ◽

2015 ◽

pp. 153-159 ◽

Cited By ~ 1

Author(s):

M. M. GOVENDER ◽

A. NADAR

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Angiotensin Ii ◽

Mrna Expression ◽

Rat Model ◽

Wistar Rat ◽

Control Group ◽

Sod Activity ◽

Male Wistar Rats ◽

Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

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Effect of Non-Surgical Periodontal Therapy on Superoxide Dismutase Levels in Gingival Tissues of Chronic Periodontitis Patients: A Clinical and Spectophotometric Analysis

Disease Markers ◽

10.1155/2013/269027 ◽

2013 ◽

Vol 34 (5) ◽

pp. 305-311 ◽

Cited By ~ 4

Author(s):

Laxmi Sukhtankar ◽

Anita Kulloli ◽

Rahul Kathariya ◽

Sharad Shetty

Keyword(s):

Superoxide Dismutase ◽

Chronic Periodontitis ◽

Inflammatory Cells ◽

Periodontal Therapy ◽

Periodontal Pocket ◽

Gingival Tissue ◽

Control Group ◽

Clinical Parameters ◽

Sod Activity ◽

Tissue Samples

BACKGROUND: Superoxide dismutase (SOD), an antioxidant acting against superoxide (oxygen radical, O2.-), it is released in inflammatory pathways and causes connective tissue breakdown. Increased SOD activity in inflamed gingiva may indicate increased O2.-radical generation by neutrophils and other inflammatory cells at the diseased site. The aim of the study was to evaluate the effects of non-surgical periodontal therapy (NSPT) on SOD levels in gingival tissues of chronic periodontitis patients.METHODS: Forty subjects: 20 periodontally healthy (Control) and 20 chronic periodontitis (Test); age range 24–55 years were recruited. Gingival tissue samples were collected by excising the inner lining of the periodontal pocket at baseline (prior to non-surgical periodontal therapy) and 2 months post therapy. In controls, tissue samples were obtained immediately after tooth extraction scheduled for orthodontic reasons. Clinical parameters included probing depth, clinical attachment level, gingival index, bleeding index, plaque index. SOD activities were assessed spectrophotometrically at baseline and 2 months post NSPT, results were analysed statistically.RESULTS: At baseline, patients with chronic periodontitis had higher mean SOD activity (2.73 ± 1.36) than the control subjects (1.12 ± 1.13) withp= 0.00003 (p< 0.05). At 2 months post NSPT median SOD level (1.00) had come close to median SOD value of control group (0.85);p= 0.99 (p> 0.05). The resolution of inflammation with successful NSPT resulted in decreased SOD levels as in control group. Clinical parameters in patients with chronic periodontitis showed a significant improvement 2 months post NSPT (p< 0.05).CONCLUSION: Non-surgical periodontal therapy significantly improves the clinical parameters and restores previously increased SOD levels to normal in chronic periodontitis patients.

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Erythropoietin alters the pharmacokinetics of organic anions mainly eliminated by the kidney in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0166 ◽

2021 ◽

Vol 99 (4) ◽

pp. 368-377

Author(s):

María Julia Severin ◽

María Herminia Hazelhoff ◽

Romina Paula Bulacio ◽

María Eugenia Mamprin ◽

Anabel Brandoni ◽

...

Keyword(s):

Organic Anion ◽

Elimination Rate ◽

Renal Tissue ◽

Organic Anions ◽

Saline Control ◽

Control Group ◽

Anion Transporters ◽

Male Wistar Rats ◽

Pah Clearance ◽

Renal Expression

Erythropoietin (EPO) is a cytokine originally used for its effects on the hematopoietic system, and is widely prescribed around the world. In the present study, the effects of EPO administration on p-aminohippurate (PAH, a prototype organic anion) pharmacokinetics and on the renal expression of PAH transporters were evaluated. Male Wistar rats were treated with EPO or saline (control group). After 42 h, PAH was administered, and plasma samples were obtained at different time points to determine PAH levels. PAH levels in renal tissue and urine were also assessed. The renal expression of PAH transporters was evaluated by Western blotting. EPO-treated rats showed an increase in PAH systemic clearance, in its elimination rate constant, and in urinary PAH levels, while PAH in renal tissue was decreased. Moreover, EPO administration increased the expression of the transporters of the organic anions evaluated. The EPO-induced increase in PAH clearance is accounted for by the increase in its renal secretion mediated by the organic anion transporters. The goal of this study is to add important information to the wide knowledge gap that exists regarding drug–drug interactions. Owing to the global use of EPO, these results are useful in terms of translation into clinical practice.

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Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00611.2004 ◽

2005 ◽

Vol 289 (5) ◽

pp. E776-E783 ◽

Cited By ~ 24

Author(s):

Juan Manuel Moreno ◽

Isabel Rodríguez Gómez ◽

Rosemary Wangensteen ◽

Antonio Osuna ◽

Pablo Bueno ◽

...

Keyword(s):

Antioxidant Enzymes ◽

Renal Cortex ◽

Control Group ◽

Antioxidant Treatment ◽

Sod Activity ◽

Cardiac Tissues ◽

Male Wistar Rats ◽

A Cell ◽

Plasma Malondialdehyde ◽

Related Increase

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 μg·rat−1·day−1. In experiment II, tempol was orally administered (18 mg·kg−1·day−1) to control and T4-treated (75 μg·rat−1·day−1) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

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Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression

BioMed Research International ◽

10.1155/2021/2195238 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Zahra Eslamifar ◽

Abbas Moridnia ◽

Susan Sabbagh ◽

Reza Ghaffaripour ◽

Leila Jafaripour ◽

...

Keyword(s):

Gene Expression ◽

Uric Acid ◽

Single Dose ◽

Gallic Acid ◽

Biochemical Parameters ◽

Standard Condition ◽

Renal Tissue ◽

Control Group ◽

Male Wistar Rats ◽

Histopathological Studies

Background. Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin’s dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. Method. Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. Results. The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. Conclusion. Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

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Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy

Romanian Journal of Internal Medicine ◽

10.1515/rjim-2016-0006 ◽

2016 ◽

Vol 54 (1) ◽

pp. 54-62 ◽

Cited By ~ 1

Author(s):

Elena Bălăşescu ◽

Mirela Cioplea ◽

Alice Brînzea ◽

Roxana Nedelcu ◽

Sabina Zurac ◽

...

Keyword(s):

Cell Death ◽

Diabetic Nephropathy ◽

Renal Tissue ◽

Ultrastructural Changes ◽

Control Group ◽

Caspase 9 ◽

Tissue Samples ◽

Diabetic Kidney ◽

Variable Expression ◽

Positive Immunostaining

Introduction. Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients. Methods. We analyzed 48 human kidney tissue samples divided into two study groups: the research group (43 renal tissue samples from diabetic or prediabetic patients), and the control group (5 renal tissue samples from patients without diabetes). Immunohistochemistry revealed expression of Bcl-2, APAF-1, CD-95 and Caspase-9 in the renal cortical structures. Statistical analysis was also performed (significance level P<0.05). Results. We found a variable expression of the antiapoptotic Bcl-2 with a decrease of Bcl-2 expression in diabetes. The control samples render evident intensely positive immunostaining for CD-95. In diabetes and diabetic nephropathy, there was positive immunostaining for APAF-1 at tubular cell level. Nuclear and cytoplasmic positivity for Caspase-9 was more frequently recorded as kidney damage progresses. APAF-1 and Caspase-9 positivity are arguments for an intrinsic apoptotic mechanism of cell death in diabetic nephropathy. Conclusion. The mechanisms of apoptotic cell death identified in diabetic kidney samples prove that Bcl-2, CD-95, APAF-1 and Caspase-9 represent reliable markers of cell death in human renal tissue. Our results support the hypothesis that apoptosis is a pathogenic and initiator mechanism of renal remodeling in diabetic kidney disease.

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Short-term effects of troxerutin (vitamin P4) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0653 ◽

2017 ◽

Vol 95 (6) ◽

pp. 708-713

Author(s):

Mohammad Zamanian ◽

Ali Shamsizadeh ◽

Ali Esmaeili Nadimi ◽

Mohammadreza Hajizadeh ◽

Fatemeh Allahtavakoli ◽

...

Keyword(s):

Gene Expression ◽

Muscle Fatigue ◽

Biochemical Parameters ◽

Hepatic Tissue ◽

Control Group ◽

Short Term ◽

Sod Activity ◽

Male Wistar Rats ◽

Swimming Test ◽

And Control

In the current study, the effects of troxerutin (TRX) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats was investigated. Forty male Wistar rats were randomly divided into 4 groups and designated as control and TRX treatment at 75 (TRX75), 150 (TRX150), and 300 mg/kg per day (TRX300). The treated groups and control group received TRX and water orally for 7 days. After an exhaustive swimming test on the 7th day, all animals were euthanized immediately and several biochemical parameters related to fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue were measured. Our results showed that the exhaustion swimming time in the TRX300 groups significantly increased 1.2-fold compared with the control group (P < 0.001). TRX300 significantly reduced ALT (P < 0.05) activity and increased liver SOD activity compared with the control group (P < 0.01). Additionally, TRX significantly reduced the liver mRNA expressions of Bax (P < 0.001) and increased the Bcl-2/Bax ratio (P < 0.001) compared with the control group. Based on our data, TRX possesses anti-apoptotic and hepatoprotective action following exhaustive swimming exercise.

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Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms22052264 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2264

Author(s):

Michaela Shishmanova-Doseva ◽

Lyudmil Peychev ◽

Lyubka Yoanidu ◽

Yordanka Uzunova ◽

Milena Atanasova ◽

...

Keyword(s):

Oxidative Stress ◽

Status Epilepticus ◽

Control Level ◽

Epileptic Activity ◽

Control Group ◽

Anticonvulsant Effect ◽

Sod Activity ◽

Inflammatory Damage ◽

Male Wistar Rats ◽

Early Effects

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

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