Sulfasalazine induces mitochondrial dysfunction and renal injury

Niknahad, Hossein; Heidari, Reza; Mohammadzadeh, Roya; Ommati, Mohammad Mehdi; Khodaei, Forouzan; Azarpira, Negar; Abdoli, Narges; Zarei, Mahdi; Asadi, Behnam; Rasti, Maryam; Yeganeh, Babak Shirazi; Taheri, Vahid; Saeedi, Arastoo; Najibi, Asma

doi:10.1080/0886022x.2017.1399908

Cited by 72 publications

(50 citation statements)

References 56 publications

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“…Ferric reducing antioxidant power (FRAP) test was used to obtain the total antioxidant power in spinal cord tissues. [ 23 ] Briefly, the working FRAP reagent was prepared fresh (0.3M sodium acetate buffer (pH 3.6), 0.01M TPTZ, 0.04M HCl, and 0.02M FeCl3 ∙ 6H2O). Spinal cord was homogenized in cold buffer (contain Tris buffer 0.25M, 0.2M sucrose, and 5 mM DT).…”

Section: Methodsmentioning

confidence: 99%

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis

Khodaei

Khoshnoud

Heidaryfar

et al. 2020

J Biochem & Molecular Tox

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Multiple sclerosis (MS) is a well‐known neurodegenerative disorder, causing toxicity in different organs, such as spinal cord tissue. The goal of this study was to investigate the protective effect of ellagic acid (EA) against spinal cord and sciatica function in cuprizone (Cup)‐induced demyelination model. Animals were divided into six equal groups. The first group received tap water as the control. Cup group was treated with Cup (0.2% w/w in fed). EA 100 group was orally treated with EA (100 mg/kg). EA + Cup groups were orally treated with three doses of 5, 50, and 100 mg/kg of EA plus Cup (0.2% w/w). All groups received treatment for 42 days. Open field, rotarod, and gait tests were done to evaluate the behavioral changes following Cup and/or EA treatment. Also, lipid peroxidation, reactive oxygen species (ROS) content, antioxidant capacity, superoxide dismutase (SOD), and catalase enzymes activity in spinal cord was evaluated. Luxol fast blue (LFB) staining also the behavioral tests were performed to evaluate the model. Cup increased ROS levels and oxidative stress in their spinal cord tissues. Also, Cup reduced antioxidant capacity, SOD, and catalase activity. EA (especially at 100 mg/kg) prevented these abnormal changes. EA co‐treatment dose‐dependently was able to ameliorate behavioral impairments in mice that received Cup. EA might act as a protective agent in MS by modulating spinal cord function.

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Section: Methodsmentioning

confidence: 99%

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis

Khodaei

Khoshnoud

Heidaryfar

et al. 2020

J Biochem & Molecular Tox

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“…The concentration of ROS in liver tissue was quantified using the method described by Niknahad et al . [ 28 ], with some modifications. Briefly, 200 mg of liver tissue were homogenized in 2 mL of ice-cold Tris-HCl buffer (40 mM, pH = 7.4).…”

Section: Methodsmentioning

confidence: 99%

Dexamethasone counteracts hepatic inflammation and oxidative stress in cholestatic rats via CAR activation

et al. 2018

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Glucocorticoids (GCs) are currently used for the therapeutic management of cholestatic diseases, but their use and molecular mechanism remain controversial. The aims of this study were 1) to assess the therapeutic effect of a 2-week treatment with the GC dexamethasone on hepatic damage in bile duct-ligated rats; 2) to investigate its effect on the activation of the nuclear receptors (NRs) pregnane X receptor (PXR), constitutive androstane receptor (CAR) and GC receptor (GR), and NF-kB, as well as on oxidative stress and bile acid (BA) hepatic composition. Cholestasis was induced by ligation of bile duct (BDL animals) in 16 male Wistar-Kyoto rats, and eight of them were daily treated by oral gavage with 0.125 mg/ml/kg DEX for 14 days. Eight Sham-operated rats were used as controls. Severity of cholestasis was assessed histologically and on plasma biochemical parameters. The nuclear expression of NF-kB (p65), GR, PXR and CAR was measured in hepatic tissue by Western Blot. Oxidative stress was evaluated by measuring malondialdehyde, carbonylated proteins, GHS and ROS content in rat livers. LC-MS was used to measure the plasma and liver concentration of 7 BAs. Histological findings and a significant drop in several markers of inflammation (p65 nuclear translocation, mRNA expressions of TNF-α, IL-1β, IL-6) showed that DEX treatment reversed cholestasis-induced inflammation, and similar results have been obtained with oxidative stress markers. The nuclear expression of p65 and CAR were inversely correlated, with the latter increasing significantly after DEX treatment (p<0.01 vs vehicle). Hepatic BA levels tended to drop in the untreated cholestatic rats, whereas they were similar to those of healthy rats in DEX-treated animals. Plasma BAs decreased significantly in DEX-treated animals with respect to untreated cholestatic rats. In conclusion, DEX reduces inflammation and oxidative stress in BDL rats, and probably CAR is responsible for this effect. Therefore, this NR represents a promising pharmacological target for managing cholestatic and inflammatory liver diseases.

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“…Mitochondrial injury plays a key role in experimental AKI models triggered by sepsis [94,97,98], IRI [99][100][101][102][103], and nephrotoxicity [104][105][106]. Mitochondrial damage in AKI is associated with mitochondrial fragmentation [107], reduced mitochondrial mass [108], mitochondrial swelling and cristae disruption [109,110], apoptosis [111], and, in general, with impaired mitochondrial function [104][105][106]. Mutations or large deletions on mtDNA or nuclear genes encoding for mitochondrial proteins may result in kidney cysts or glomerular or tubular disease [112][113][114][115][116].…”

Section: Morphological and Functional Changes Of Mitochondriamentioning

confidence: 99%

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

et al. 2020

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Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.

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Sulfasalazine induces mitochondrial dysfunction and renal injury

Cited by 72 publications

References 56 publications

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis

Dexamethasone counteracts hepatic inflammation and oxidative stress in cholestatic rats via CAR activation

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

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