Sulfasalazine-Induced Hepatic Injury in an Ex Vivo Model of Isolated Perfused Rat Liver and the Protective Role of Taurine

Heidari, Reza; Sadeghi, N; Azarpira, Negar; Niknahad, Hossein

doi:10.15171/ps.2015.39

Cited by 18 publications

(14 citation statements)

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“…Some investigations indicated the involvement of oxidative stress and its consequent events in this complication [8,9]. Oxidative stress and its consequences also seem to be involved in other sulfasalazine side effects including infertility and hepatic injury [40][41][42]. In line with previous investigations, we found that sulfasalazine significantly increased oxidative stress biomarkers in the kidney tissue (Table 1).…”

Section: Discussionsupporting

confidence: 90%

Sulfasalazine induces mitochondrial dysfunction and renal injury

et al. 2017

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Sulfasalazine is a commonly used drug for the treatment of rheumatoid arthritis and inflammatory bowel disease. There are several cases of renal injury encompass sulfasalazine administration in humans. The mechanism of sulfasalazine adverse effects toward kidneys is obscure. Oxidative stress and its consequences seem to play a role in the sulfasalazine-induced renal injury. The current investigation was designed to investigate the effect of sulfasalazine on kidney mitochondria. Rats received sulfasalazine (400 and 600 mg/kg/day, oral) for 14 consecutive days. Afterward, kidney mitochondria were isolated and assessed. Sulfasalazine-induced renal injury was biochemically evident by the increase in serum blood urea nitrogen (BUN), gamma-glutamyl transferase (c-GT), and creatinine (Cr). Histopathological presentations of the kidney in sulfasalazine-treated animals revealed by interstitial inflammation, tubular atrophy, and tissue necrosis. Markers of oxidative stress including an increase in reactive oxygen species (ROS) and lipid peroxidation (LPO), a defect in tissue antioxidant capacity, and glutathione (GSH) depletion were also detected in the kidney of sulfasalazine-treated groups. Decreased mitochondrial succinate dehydrogenase activity (SDA), mitochondrial depolarization, mitochondrial GSH depletion, increase in mitochondrial ROS, LPO, and mitochondrial swelling were also evident in sulfasalazine-treated groups. Current data suggested that oxidative stress and mitochondrial injury might be involved in the mechanism of sulfasalazine-induced renal injury. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 90%

Sulfasalazine induces mitochondrial dysfunction and renal injury

et al. 2017

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“…The perfusate buffer volume was 200 mL in all experiments. 24,49 Study procedure Rat liver was perfused with simple KBH and amino acid containing KBH for 12 consecutive hours. Hepatic injury was assessed at scheduled time intervals (every 3 hours).…”

Section: Isolated Perfused Rat Liver Preparationmentioning

confidence: 99%

“…The mixture was vortexed and centrifuged (10,000 g, 15 minutes, 4ºC). 49,54 Then, 2 mL of the supernatant was added to 4 mL of Tris-HCl buffer (40 mM, pH = 8.9) and 100 µl of freshly-prepared DTNB solution (10 mM in methanol). 53,55 The absorbance of developed yellow color was measured (λ = 412 nm using an EPOCH ® plate reader (Highland park, USA).…”

Section: Liver Glutathione Contentmentioning

confidence: 99%

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Amino Acid-Containing Krebs-Henseleit Buffer Protects Rat Liver in a Long-Term Organ Perfusion Model

et al. 2018

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Background: The liver is vulnerable to the toxicity induced by xenobiotics. On the other hand, it has been found that several endogenously-found amino acids have hepatoprotective properties. The current study was designed to evaluate the effect of taurine, glycine, and histidine on the liver function in an ex vivo model of prolonged organ perfusion. Methods: Rat liver was isolated and perfused with a hemoglobin- and albumin-free Krebs‑Henseleit buffer (KBH). Liver injury biomarkers were monitored at scheduled time intervals. Results: The perfusate level of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the potassium ion (K+) were gradually increased in control (Only KBH) group. The histopathological evaluation also revealed significant necrosis, sinusoidal dilation, and pyknosis in control liver. Moreover, significant increase in lipid peroxidation and depletion of hepatic glutathione stores were detected in the control group. It was found that taurine (5, 10 and 20 mM) and glycine (5, 10 and 20 mM)-containing KBH buffer significantly decreased the perfusate level of liver injury biomarkers. Furthermore, lower liver tissue pathological changes, decreased lipid peroxidation, and higher glutathione content was detected in amino acid-treated groups. Histidine administration showed no significant protective effect on liver injury in the current study. On the other hand, combination amino acid administration (glycine and taurine) showed a better hepatoprotective profile. Conclusion: The data obtained from the current study might help to provide safe hepatoprotective agents against xenobiotics-induced hepatotoxicity or preserve liver functionality outside the body.

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“…A Mindray ® BS-200 auto-analyzer (Mindray chemistry analyzers for low-volume laboratories, Guangzhou, China) and commercial kits (Pars Azmun ® , Tehran, Iran), were used to evaluate serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate amino transferase (AST) in PTU-treated mice. 25,26 Liver samples were fixed in buffered formalin solution (0.4% sodium phosphate monobasic, NaH2PO4, 0.64% sodium phosphate dibasic, Na2HPO4, and 10% formaldehyde in distilled water) and used for tissue histopathological assessment. 27,28 Paraffinembedded blocks of liver tissue were prepared and stained with haematoxylin and eosin (H&E) before viewing by a light microscope (Olympus CX21 ® , Japan).…”

Section: In Vivo Experimentsmentioning

confidence: 99%