Hypoxia alters P-gp Expression and Activity in Three Different Rat Intestinal Modles: Implications for Levofloxacin Delivery
Journal: International Journal of Clinical Pharmacology & Toxicology (IJCPT) (Vol.10, No. 1)Publication Date: 2021-06-22
Authors : Li Wen-bin Jiang Ze-juan Wang Rong Zhao An-peng Li Xue Luo Bing-Feng Yang Xi;
Page : 331-338
Keywords : ;
Abstract
Objective: To investigate the difference in P-glycoprotein (P-gp) expression and the absorption of levofloxacin in rat small intestines between high altitude and plain areas. Methods: Wistar rats kept in Shanghai (representing the plain area) were used as the normoxic group, and rats rapidly exposed to high altitude via flights were used as the hypoxic group. Reverse transcription-quantitative PCR and western blotting were performed to assess the mRNA and protein expression of P-gp, respectively. The everted intestinal sac model, the in-situ single-pass perfused intestinal model, and the whole animal model were used to investigate levofloxacin absorption in rat intestines. Results: The mRNA and protein expression levels of P-gp were significantly decreased (by 50.80% and 71.30%) in the hypoxic group compared with those in the normoxic group. In the everted intestinal sac model, the maximum values of levofloxacin absorption in the hypoxic group were 19.99%, 29.29%, and 45.47% in the duodenum, jejunum, and ileum segments, respectively, at 75 min (P<0.05). The permeability parameters (Peff) of the hypoxic group increased by 32 56.16%, 226.00%, 77.74%, and 141.00% at 30-60 min, 60-90 min, 90-120 min, and 120-150 min, respectively (P<0.05). In the hypoxic group, the area-under-the-curve of plasma P-gp increased by 5.05-, 4.90-, and 3.85-fold, respectively, after the oral administration of low-, medium-, and high-dose levofloxacin compared with those in the normoxic group, while the peak plasma concentration increased by 6.04-, 3.28-, and 2.87-fold, respectively. Discussion: Hypoxia downregulated P-gp expression and increased levofloxacin absorption in rats at high altitudes. Understanding differential mechanisms of drug transporters under hypoxia is important for informed drug administration at high altitudes.
Other Latest Articles
- Evaluation of Fever Management Practices in Rural India
- Underdiagnosed Paraquat Induced Pneumothorax and Pneumomediastinum, The “Daisley Barton Syndrome”: A Clinical Feature Of Paraquat-Induced Acute Lung Injury
- Mechanism Based Precision Diagnostics for BRCA1-Associated TNBC
- A Healthy Lifestyle for Preventing Chronic Diseases among Active Older Adults Aged Over 80 Years: A Case Study in Tron District, Uttaradit Province, Northern Thailand
- Treatment of Chronic Hepatitis C: An Experience Report from a Referral Center in Northeastern Brazil
Last modified: 2021-10-28 16:27:53