scholarly journals Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 511 ◽  
Author(s):  
Yunji Wang ◽  
Fang Feng
Keyword(s):  
Tissue Distribution ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Sprague Dawley ◽  
Gardenia Jasminoides ◽  
Sprague Dawley Rats ◽  
Q Exactive ◽  
Serum Biochemical ◽  
Endogenous Metabolites ◽  
Liver Tissues

With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.

scholarly journals Study on the pharmacokinetics, tissue distribution and excretion of laurolitsine from Litsea glutinosa in Sprague-Dawley rats

2021 ◽  
Vol 59 (1) ◽  
pp. 884-892
Author(s):  
Yin-Feng Tan ◽  
Rui-Qi Wang ◽  
Wen-Ting Wang ◽  
Ying Wu ◽  
Ning Ma ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Litsea Glutinosa

Pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats and metabolism of ACT001

2019 ◽  
Vol 1104 ◽  
pp. 29-39 ◽  
Author(s):  
Xiao-Nan Xi ◽  
Ning Liu ◽  
Qian-qian Wang ◽  
Hai-Ting Wu ◽  
Hai-Bo He ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 388
Author(s):  
Elizabeth Soria-Castro ◽  
Verónica Guarner-Lans ◽  
María Elena Soto ◽  
María del Carmen Avila-Casado ◽  
Linaloe Manzano Pech ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Acid Metabolism ◽  
Rat Kidney ◽  
Group Iv ◽  
Sprague Dawley ◽  
Group Iii ◽  
Collapsing Glomerulopathy ◽  
Fa Composition ◽  
Group I ◽  
Sprague Dawley Rats

Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP (p ≤ 0.01) in comparison with the C, SS and HS rats. The FA composition of the serum of rats that received the CG serum showed an increase in palmitic acid (PA) and a decrease in arachidonic acid (AA) when compared to serum from HS (p ≤ 0.02). In rats receiving the CG serum, there was also a decrease in the AA in the kidney but there was an increase in the PA in the serum and kidney (p ≤ 0.01). These results suggest that the administration of serum from CG patients to rats induces alterations in FA metabolism including changes in PA and in AA, which are precursors for the biosynthesis of the prostaglandins that are involved in the elevation of SBP and in renal injury. These changes may contribute to collapsing glomerulopathy disease.

Stereoselective pharmacokinetics and tissue distribution of levodropropizine after administration of pure levodropropizine and the rac-dropropizine to Sprague–Dawley rats

Xenobiotica ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 222-231 ◽  
Author(s):  
Bhavesh Babulal Gabani ◽  
Umesh Todmal ◽  
Neeraj Kumar Saini ◽  
Vinod A. Balakrishna ◽  
Suresh P. Sulochana ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stereoselective Pharmacokinetics

Effect of urinary alkalinisation and acidification on the tissue distribution of hexachlorophene in rats

1995 ◽  
Vol 14 (10) ◽  
pp. 795-800 ◽  
Author(s):  
RJ Flanagan ◽  
M. Ruprah ◽  
AV Strutt ◽  
P. Malarkey ◽  
A. Cockburn
Keyword(s):  
Oxidative Phosphorylation ◽  
Sodium Bicarbonate ◽  
Tissue Distribution ◽  
Ammonium Chloride ◽  
Acute Poisoning ◽  
Sprague Dawley ◽  
Urine Ph ◽  
Sprague Dawley Rats ◽  
Median Plasma ◽  
Liver And Kidney

1 Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2 We studied the effects of urine alkalinisation and acidi fication on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3 Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) fol lowed by either HCP (180 mg kg-1) or vehicle alone. 4 Urine pH, body mass and body temperature were moni tored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5 No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver — median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride signifi cantly increased median HCP concentrations in liver and kidney — median plasma HCP was also increased but not significantly. 6 The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncou plers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.

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