Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity

Smyth, Rosemary; Turton, John; Clarke, Christopher J.; York, Malcolm; Dare, Theo; Lane, Catherine; Munday, Michael R.

doi:10.1016/j.fct.2008.05.041

Cited by 16 publications

(27 citation statements)

References 51 publications

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“…Furthermore, serum urea and creatinine levels were only significantly increased above control base line levels in animals treated at dose levels of 1.2 ml/kg CCl 4 and above (Smyth et al 2008). Investigations were carried out with urine collected from rats following the administration of a single dose of CCl 4 at dose levels below 1.2 ml/kg (0.4 and 0.8 ml/kg) (Smyth et al 2008). Urine samples were analysed by surface enhanced laser desorption/ionisation technology and by SDS-PAGE.…”

Section: Introductionmentioning

confidence: 86%

“…Previously, we have investigated urinary markers of hepatic injury after the administration of a single dose of CCl 4 to female Hanover Wistar rats (Smyth et al 2008). In these earlier studies, we demonstrated nephrotoxicity using histopathological evaluation in CCl 4 -treated rats at dose levels of 1.2 ml/kg and above; but below this dose level, the kidneys were histopathologically normal and no renal lesions were identified.…”

Section: Introductionmentioning

confidence: 93%

“…CCl 4 -induced oxidative stress plays a role in Kupffer cell activation and fibrogenesis (Rivera et al 2001). We have previously reported histopathological changes and markers of inflammation in CCl 4 -induced hepatic injury in the female Hanover Wistar rat (Giffen et al 2003), and more recently described CCl 4 -induced models of hepatic fibrosis and acute liver injury, also in the female Hanover Wistar rat (Smyth et al 2007(Smyth et al , 2008.…”

Section: Introductionmentioning

confidence: 96%

“…Both techniques demonstrated the presence of copper/zinc superoxide dismutase (Cu/Zn SOD) in the urine of rats with hepatic injury at time points from 12 h post-dosing, and reaching a peak at 36 h post-dosing. Superoxide dismutase (SOD) activity in urine was found to be increased by 61-fold in CCl 4 -treated rat urine (Smyth et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…In these earlier studies, we demonstrated nephrotoxicity using histopathological evaluation in CCl 4 -treated rats at dose levels of 1.2 ml/kg and above; but below this dose level, the kidneys were histopathologically normal and no renal lesions were identified. Furthermore, serum urea and creatinine levels were only significantly increased above control base line levels in animals treated at dose levels of 1.2 ml/kg CCl 4 and above (Smyth et al 2008). Investigations were carried out with urine collected from rats following the administration of a single dose of CCl 4 at dose levels below 1.2 ml/kg (0.4 and 0.8 ml/kg) (Smyth et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Proteomic investigation of urinary markers of carbon-tetrachloride-induced hepatic fibrosis in the Hanover Wistar rat

et al. 2008

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Proteomic techniques such as two-dimensional gel electrophoresis (2-DGE) and mass spectrometry have become important tools for the identification of novel biomarkers of toxicity and disease. Ideally, such biomarkers need to be sensitive and organ specific, but, recently, it has become apparent that it would be an additional benefit to be able to measure biomarkers in samples obtained using non-invasive methods. The present study is concerned with the identification of novel urinary markers of hepatic fibrosis. In a carbon-tetrachloride-induced liver fibrosis rat model, analysis of urine by 2-DGE revealed an increase in the concentration of a number of proteins in animals with hepatic fibrosis. Using in-gel trypsin digest and nano-scale liquid chromatography combined with electrospray ionisation tandem mass spectrometry, protein spots were identified as copper/zinc superoxide dismutase, D: -dopachrome tautomerase, beta-2-microglobulin and neutrophil gelatinase associated lipocalin. These proteins are known to have important roles in the inflammatory response.

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Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Proteomic investigation of urinary markers of carbon-tetrachloride-induced hepatic fibrosis in the Hanover Wistar rat

et al. 2008

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Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches

Rakib

Ahmed

et al. 2019

Food Science & Nutrition

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This research describes an investigation of the antipyretic and hepatoprotectiveproperties of both a crude organic extract and various subfractions of the ethnomedicinal plant Tinospora crispa, using appropriate animal models. In an attempt to identify potential lead hepatoprotective compounds, in silico experiments were utilized.Antipyretic activity was assessed via the Brewer's yeast-induced pyrexia method, while hepatoprotective effects were evaluated in a carbon tetrachloride (CCl 4 )induced animal model. A computer-aided prediction of activity spectra for substances (PASS) model was applied to a selection of documented phytoconstituents, with the aim of identifying those compounds with most promising hepatoprotective effects.Results were analyzed using Molinspiration software. Our results showed that both the methanol extract (METC) and various subfractions (pet ether, PEFTC; n-hexane, NHFTC; and chloroform, CFTC) significantly (p < .05) reduced pyrexia in a dose-dependent manner. In CCl 4 -induced hepatotoxicity studies, METC ameliorated elevated hepatic markers including serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), and total bilirubin. Malondialdehyde (MDA) levels were significantly reduced, while superoxide dismutase (SOD) levels were significantly increased. Among a selection of metabolites of T. crispa, genkwanin was found to be the most potent hepatoprotective constituent using PASS predictive models. These results demonstrate that both the methanolic extract of T. crispa and those fractions containing genkwanin may offer promise in reducing pyrexia and as a source of potential hepatoprotective agents. K E Y W O R D S antipyretic, CCl 4 -induced hepatotoxicity, hepatoprotective, in silico studies, PASS prediction, Tinospora crispa, yeast-induced pyrexia How to cite this article: Rakib A, Ahmed S, Islam MA, et al. Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches. Food Sci Nutr. 2020;8:547-556. https ://doi.

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Urinary biomarkers in hexachloro‐1:3‐butadiene‐induced acute kidney injury in the female Hanover Wistar rat; correlation of α‐glutathione S‐transferase, albumin and kidney injury molecule‐1 with histopathology and gene expression

Swain

Turton

Scudamore

et al. 2010

J of Applied Toxicology

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Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair.

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Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity

Cited by 16 publications

References 51 publications

Proteomic investigation of urinary markers of carbon-tetrachloride-induced hepatic fibrosis in the Hanover Wistar rat

Proteomic investigation of urinary markers of carbon-tetrachloride-induced hepatic fibrosis in the Hanover Wistar rat

Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches

Urinary biomarkers in hexachloro‐1:3‐butadiene‐induced acute kidney injury in the female Hanover Wistar rat; correlation of α‐glutathione S‐transferase, albumin and kidney injury molecule‐1 with histopathology and gene expression

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