Apoptosis-inducing factor plays a role in the pathogenesis of hepatic and renal injury during cholestasis

Ghanbarinejad, Vahid; Jamshidzadeh, Akram; Khalvati, Bahman; Farshad, Omid; Li, Huifeng; Shi, Xinjian; Chen, Yuanyu; Ommati, Mohammad Mehdi; Heidari, Reza

doi:10.1007/s00210-020-02041-7

Cited by 26 publications

(14 citation statements)

References 67 publications

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“…Afterward, the supernatant was treated with 100 µl of ice‐cooled 4 M KOH solution. [ 20,35 ] Samples were centrifuged (15,000 g , 10 min, 4°C) and 25 µl of the supernatant was injected into an HPLC system consisted of a C‐18 column. An isocratic method was used, and the mobile phase was composed of KH 2 PO 4 (100 mM, pH 7 adjusted with KOH), tetrabutylammonium hydroxide (1 mM), and acetonitrile (2.5% v/v).…”

Section: Methodsmentioning

confidence: 99%

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Disturbed mitochondrial redox state and tissue energy charge in cholestasis

Ghanbarinejad

Ommati

Jia

et al. 2021

J Biochem & Molecular Tox

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The liver is the primary organ affected by cholestasis. However, the brain, skeletal muscle, heart, and kidney are also severely influenced by cholestasis/cirrhosis. However, little is known about the molecular mechanisms of organ injury in cholestasis. The current study was designed to evaluate the mitochondrial glutathione redox state as a significant index in cell death. Moreover, tissue energy charge (EC) was calculated. Rats underwent bile duct ligation (BDL) and the brain, heart, liver, kidney, and skeletal muscle mitochondria were assessed at scheduled time intervals (3, 7, 14, and 28 days after BDL). A significant decrease in mitochondrial glutathione redox state and EC was detected in BDL animals. Moreover, disturbed mitochondrial indices were evident in different organs of BDL rats. These data could offer new insight into the mechanisms of organ injury and the source of oxidative stress during cholestasis and might provide novel therapeutic strategies against these complications.

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Section: Methodsmentioning

confidence: 99%

“…Afterward, the supernatant was treated with 100 µl of ice-cooled 4 M KOH solution. [20,35] Samples were centrifuged (15,000g, 10 min, 4°C) and 25 µl of the supernatant was injected into an HPLC system consisted of a C-18…”

Section: Mitochondrial Atp Contentmentioning

confidence: 99%

Disturbed mitochondrial redox state and tissue energy charge in cholestasis

Ghanbarinejad

Ommati

Jia

et al. 2021

J Biochem & Molecular Tox

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“…Urine samples were collected (200 µl) during animal handling and diluted with ice-cold normal saline (200 µl, 4°C) [ 32 , 33 ]. Afterward, samples were centrifuged (1000 g, 5 min, 4°C), and the clear supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were mixed well and centrifuged (10,000 g, 10 min, 4°C). Finally, the absorbance of developed color in the upper phase was measured at λ = 532 nm using the EPOCH Plate reader (BioTek, USA) [ 15 , 33 , 51 ].…”

Section: Methodsmentioning

confidence: 99%

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Ommati¹,

Hojatnezhad²,

Abdoli³

et al. 2021

ceh

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Aim of the study Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated. Material and methods Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored. Results Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines. Conclusions These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

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“…We also examined whether BDL- and LPS-induced inflammation affected mGSH levels. It is well known that the kidneys of BDL mice are inflamed extrahepatic organs [ 13 , 19 ]. In addition, we conducted an in vitro study using human clear cell renal carcinoma (KMRC-1) cells to clarify the mechanism of regulation of SLC25A39/40 expression in the kidneys following LPS treatment.…”

Section: Introductionmentioning

confidence: 99%

Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment

Kawase

Hatanaka²,

Matsuda³

et al. 2022

IJMS

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SLC25A39/40, involved in mitochondrial GSH (mGSH) import from the cytoplasm, is essential for protection against oxidative stress and mitochondrial dysfunction. We examined the effects of cholestasis, through bile duct ligation (BDL) and lipopolysaccharide (LPS)-induced inflammation in mice, on Slc25a39/40 expression. Additionally, we used human clear cell renal carcinoma (KMRC-1) cells to elucidate the mechanism of regulation of SLC25A39/40 expression in the kidneys after LPS treatment. BDL resulted in a decrease in Slc25a39 mRNA in the liver and a decrease in Slc25a39/40 mRNA and protein in the kidneys. Consequently, there was a significant decrease in mGSH levels in the kidneys of BDL mice compared with those in sham mice. LPS treatment resulted in increased Slc25a40 expression in the kidneys. In KMRC-1 cells, the combination treatment of LPS-RS or FPS-ZM1 with LPS suppressed the LPS-induced increase in SLC25A40, suggesting that SLC25A40 expression could be regulated by the signaling pathway via toll-like receptor 4 and the receptor for advanced glycation end products, respectively. Our findings contribute to understanding the role of mGSH in the maintenance of the mitochondrial redox state. To the best of our knowledge, this is the first study that demonstrates the changes in Slc25a39/40 expression in mice with cholestasis-associated renal injury and LPS-induced inflammation.

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Apoptosis-inducing factor plays a role in the pathogenesis of hepatic and renal injury during cholestasis

Cited by 26 publications

References 67 publications

Disturbed mitochondrial redox state and tissue energy charge in cholestasis

Disturbed mitochondrial redox state and tissue energy charge in cholestasis

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment

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