Drug-drug interaction of acetaminophen and roxithromycin with the cocktail of cytochrome P450 and hepatotoxicity in rats

Abstract

Acetaminophen (APAP) and roxithromycin (ROX) are often used in combination in clinical practice. To evaluate their drug-drug interactions (DDIs) and the hepatotoxicity of co-administration, rats were randomly separated into four groups: Control, APAP (50 mg/kg), ROX (5.5 mg/kg) and APAP-ROX (50 mg/kg and 5.5 mg/kg, respectively). The pharmacokinetic parameters between APAP and ROX were assayed by HPLC, and a cocktail method was used to evaluate the activities of cytochrome (CYP) 450. The liver microsome CYP2E1 protein was detected using Western blot. The levels of plasma parameters, mRNA levels of inflammatory factors (TNF-α, INF-γ, VCAM-1, CXCL-1 and STAT-3) and antioxidant factors (Nrf-2, GSTA, GCLC-1, HO-1 and NQO1) were determined using real-time PCR, along with the observation on histopathological changes in the liver tissue. APAP and ROX co-treatment significantly increased CYP2E1 activity, decreased CYP2D6 activity and prolonged APAP and ROX clearance. Co-treatment increased mRNA expressions of TNF-α, NQO1 and MDA while decreasing GPX and SOD levels. Histopathological evidence showed the changes of liver tissues in terms of structure, size and tight arrangement. This study confirmed that a combination of APAP and ROX inhibited APAP metabolism and that the peak concentration of ROX was delayed. The resulting high level of CYP2E1 may induce oxidative stress and cause liver damage.

Synthesis of Escherichia coli OmpA Oral Nanoparticles and Evaluation of Immune Functions against the Major Etiologic Agent of Cow Mastitis

“…Briefly, the samples were treated with different reagents, reacted under the specified conditions, 200 μL of the reaction solution was transferred to the wells, and the absorbance values at different wavelengths were determined with a microplate reader. The content or activity of each factor was calculated by the specific calculation formula of each factor [ 21 ].…”

“…mRNA was isolated from the spleen, liver, and kidney tissues using an RNA isolation kit (TAKARA, Tokyo, Japan) following the manufacturer’s instructions, as described previously [ 21 ]. Briefly, the mRNA was reverse-transcribed to cDNA using a PrimeScript RT Master Mix kit (TAKARA, Tokyo, Japan), and cDNAs were amplified using the primers shown in Table 1 .…”

“…The preparation of pathological sections of mice liver and kidney involved dehydration, transparency, sectioning, and hematoxylin and eosin (H&E) staining [ 21 ]. Briefly, the liver and kidney tissues were dehydrated using an alcohol gradient for 1 h and then placed in an alcohol:xylene mixture (1:1, v/v ) for 30 min, xylene for 8 min, a xylene:paraffin solution (1:1, v/v ) for 30 min, and paraffin for 1 h. Slices with a thickness of about 5 μm were cut, dried, H&E stained, observed under a microscope, and photographed (Leica, Wetzlar, Germany).…”

“…The significant difference from the respective control in all experiments was assessed by one-way analysis of variance (ANOVA) using SPSS (IBM Corporation, Chicago, IL, USA). Values of p < 0.05 were considered statistically significant [ 21 ].…”

Synthesis of Escherichia coli OmpA oral nanoparticles and evaluation of immune function against the main pathogenic bacteria of cow mastitis

“…First, mRNA was isolated from the spleen, liver, and kidney tissues using an RNA isolation kit (TAKARA, Japan) and according to the manufacturer's instructions, as described previously [21]. Brie y, the mRNA was reverse-transcribed to cDNA using a PrimeScript RT Master Mix kit (TAKARA, Japan), and cDNAs were ampli ed using the primers shown in Table 1.…”