Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism

Abiola, T; Adebayo, Oyindamola C; Babalola, O. O.

doi:10.4236/jbm.2019.712005

Cited by 9 publications

(8 citation statements)

References 38 publications

(35 reference statements)

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“…5a). In contrast with another authors that found increased levels of malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 )/ROS in smaller doses [28], NTR treated diclofenac 100 mg/kg did not increase LOOH herein. However, as we do not directly quantify reactive oxygen species, we cannot infer the absence of oxidative damage in the NTR.…”

Section: Resultscontrasting

confidence: 74%

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis

Boeing,

Lima,

Busana

et al. 2024

Drug Res (Stuttg)

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Background Diclofenac is the non-steroidal anti-inflammatory drug (NSAID) mostly prescribed worldwide, but it is highly associated with hypertension and acute kidney injury. Despite that, little information is available about the renal effects of diclofenac in hypertensive individuals, which led us to carry out this comparative study between the renal effects of this NSAID in normotensive (NTR) and spontaneously hypertensive rats (SHR). Methods Male Wistar NTR and SHR were orally treated with vehicle (V: 10 mL/kg) or diclofenac sodium (D: 100 mg/kg) once a day for 3 days. Urine volume, electrolytes excretion (Na+, K+, Cl-, and Ca2+), urea, creatinine, pH, and osmolarity were evaluated. Furthermore, blood samples and renal tissue were collected to perform biochemical and histological analysis. Results Diclofenac increased the renal corpuscle and bowman’s space in the SHR, while no microscopic changes were observed in the renal tissue of NTR. Regarding the urinary parameters, diclofenac reduced urine volume, pH, osmolarity, and all electrolytes excretion, followed by decreased urea and creatinine levels in both lineages. Moreover, it also induced hyponatremia, hypokalemia, and hypocalcemia in SHR, while reduced glutathione-S-transferase activity, lipid hydroperoxides, and nitrite levels in renal tissue. Conclusions The data presented herein demonstrated that diclofenac induces renal damage and impaired renal function in both NTR and SHR, but those effects are exacerbated in SHR, as seen by the histological changes and electrolytes balance disturbance, therefore, reinforcing that diclofenac may increase the risks of cardiovascular events in hypertensive patients.

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Section: Resultscontrasting

confidence: 74%

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis

Boeing,

Lima,

Busana

et al. 2024

Drug Res (Stuttg)

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“…This particular aspect highlights the fact that diclofenac may induce AKI via a different primary pathological mechanism. It is postulated that a mechanism related to the induction of oxidative stress and/or reduction of antioxidant capacity may be determinant for diclofenac-induced nephrotoxicity [ 14 , 15 ]. In this sense, investigations have shown that through oxidative stress, increased cytokine release, and nuclear factor κB (NFκB) activation, diclofenac may induce AKI [ 1 , 9 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway

et al. 2022

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Hesperidin is derived from citrus fruits among other plants. Hesperidin was methylated to increase its solubility, generating hesperidin methyl chalcone (HMC), an emerging flavonoid that possess anti-inflammatory and antioxidant properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful regulator of cellular resistance to oxidant products. Previous data evidenced HMC can activate Nrf2 signaling, providing antioxidant protection against diverse pathological conditions. However, its effects on kidney damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) have not been evaluated so far. Mice received a nephrotoxic dose of diclofenac (200 mg/kg) orally followed by intra-peritoneal (i.p.) administration of HMC (0.03–3 mg/kg) or vehicle. Plasmatic levels of urea, creatinine, oxidative stress, and cytokines were assessed. Regarding the kidneys, oxidative parameters, cytokine production, kidney swelling, urine NGAL, histopathology, and Nrf2 mRNA expression and downstream targets were evaluated. HMC dose-dependently targeted diclofenac systemic alterations by decreasing urea and creatinine levels, and lipid peroxidation, as well as IL-6, IFN-γ, and IL-33 production, and restored antioxidant properties in plasma samples. In kidney samples, HMC re-established antioxidant defenses, inhibited lipid peroxidation and pro-inflammatory cytokines and upregulated IL-10, reduced kidney swelling, urine NGAL, and histopathological alterations. Additionally, HMC induced mRNA expression of Nrf2 and its downstream effectors HO-1 and Nqo1, as well as reduced the levels of Keap1 protein detected in renal tissue. The present data demonstrate HMC is a potential compound for the treatment of acute renal damage caused by diclofenac, a routinely prescribed non-steroidal anti-inflammatory drug.

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“…The present study confirms previous findings that the administration of diclofenac sodium leads to an increase in serum levels of urea, uric acid, and creatinine. Urea is a byproduct of protein metabolism and its accumulation in the blood can be attributed to a decrease in glomerular filtration rate (GFR) caused by diclofenac sodium 36 . This drug inhibits the production of prostaglandins, which play a vital role in maintaining GFR.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Methanolic Extract of Broccoli (BMX) on Diclofenac Sodium (DIC)-Induced Oxidative Damage in Rat Kidney

Raeeszadeh

Simab

2022

J Lab Anim. Res

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Introduction: The objective of this study was to investigate the potential protective effect of the methanolic extract of broccoli against oxidative stress induced by diclofenac in rats. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause nephrotoxicity, hence the need to explore the therapeutic potential of medicinal plants. Materials and methods: A total of 48 adult male Wister rats with a maximum age of 2-3 months with an average weight of 220 g were randomly divided into four equal groups (12 in each group The first group was control (C) and fed physiological saline without treatment, the second group was BC which treated with broccoli methanolic extract (BMX) at a dose of 500 mg/kg/Intraperitoneal injection, the third group was DC which treated with diclofenac sodium (DIC, 100 mg/kg, Intra-muscular injection), and the fourth group was BC plus DC which treated diclofenac sodium (100 mg/kg, Intra-muscular injection) and broccoli (500 mg/kg/ Intraperitoneal injection). After blood collection, serum was isolated, and urea, creatinine, interleukin-1, and TNF-α were measured in blood serum. In kidney tissue, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. At the end of the study, the samples were taken for histopathological investigation. Results: The results of the present study indicated that diclofenac sodium causes severe kidney damage. The levels of creatinine and urea showed a significant increase in the DC group compared with the control and other treatment groups. The pro-inflammatory biomarkers in blood serum increased in the DC group and significantly decreased in the BC+DC group compared with control and other treatment groups. These changes were in line with the significant decrease of GPx and CAT enzyme levels in the DC group and its increase in the BC group. Malondialdehyde increased in the DC group and reached its lowest level in the BC group. Hyperemic changes, accumulation of inflammatory cells, and bleeding were indicators of diclofenac tissue poisoning reported in the kidney. Conclusion: The results of biochemical and histopathological showed that broccoli extract at the dosage of 500 mg/kg with strong antioxidant potential can drama a protective role against diclofenac damage in the kidney.

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Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism

Cited by 9 publications

References 38 publications

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis

The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway

Ameliorative Effect of Methanolic Extract of Broccoli (BMX) on Diclofenac Sodium (DIC)-Induced Oxidative Damage in Rat Kidney

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