Cao, G.-y. | bioRxiv Science

bioRxiv2022

Chronic Intermittent Hypobaric Hypoxia Prevents Contrast-Induced Acute Kidney Injury By Modulating The HIF-1α Signaling Pathway

The aim of this study was to explore the role of CIHH in preventing contrast-induced acute kidney injury (CI-AKI) in rats and its mechanism. Rats mean arterial pressure, heart rate, serum creatinine and blood urea nitrogen levels were measured. The kidney tissue pathological changes, superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, hypoxia inducible factor-1, Bcl-2/adenovirus E1B-19kDa-interacting protein3 (BNIP3) , cysteiny aspartate specific protease3(caspase3) and poly(ADP-ribose) polymerase (PARP) expression levels were testing. The results showed that CIHH prevented CI-AKI group mean arterial pressure, heart rate, serum creatinine and blood urea nitrogen levels were reduced, kidney tissue SOD activity was increased, MDA levels was reduced, HIF-1,BNIP3,caspase3 and PARP levels were increased than the CI-AKI group. This study indicates that CIHH pretreatment may have a protective effect on contrast-induced early kidney injury by activating the HIF-1/BNIP3 signaling pathway to regulate mitochondrial autophagy and enhance cellular anti-apoptotic and renal antioxidant capacity, for the first time.

physiology↗

bioRxiv2018

Population Pharmacokinetics Study of Morinidazole in Patients with Moderate Hepatic Impairment

ObjectiveMorinidazole is a novel third generation 5-nitroimidazole antimicrobial drug which has demonstrated substantial antibacterial activity against clinical isolates of anaerobe. The aim of this study was to build population pharmacokinetic (PPK) model of morinidazole among patients with hepatic impairment and to provide dosage adjustment strategy for morinidazole in patients with hepatic impairment and/or renal dysfunction.\n\nMethodsThe nonlinear mixed effects modeling tool NONMEM (version7.3, ICON Development Solutions) was used to develop the PPK model of morinidazole.\n\nResultsOne-compartment model was conducted to establish the morinidazole PPK model. Disease condition was the significant covariate for CL and weight was the significant covariate for V. The AUC0-{infty} was 120.44{+/-}37.05 (79.25-207.20) gxh/mL in hepatic impairment group and was 79.46{+/-}23.71 (42.94-116.75) gxh/mL in control group. The AUC0-{infty} was 164.9{+/-}44.8 gxh/mL and 77.2{+/-}23.1 gxh/mLin in the 3 subjects with both hepatic impairment and mild renal impairment and in the 3 matched healthy subjects, respectively.\n\nConclusionIt is not necessary to adjust morinidazole dosage for patients with moderate hepatic impairment without confirmed renal dysfunction. For patient with moderate hepatic and mild renal impairment, morinidazole regimen should be considered as 500mg every 24 hours. When used in patients with moderate/severe hepatic impairment combined with renal dysfunction, both dosage and interval adjustment of morinidazole should be considered.

pharmacology and toxicology↗