ABSTRACT
While cyclosporin A (CsA) is an effective immunosuppressive agent, its clinical application is limited by serious hepatorenal toxicity. However, Schisandrae chinensis fructus extract (SCE) has been previously shown to alleviate the hepatorenal damage caused by CsA. In this study, we aimed to evaluate the protective effects of SCE against hepatorenal toxicity induced by CsA. Our results revealed that SCE can prevent and treat CsA-induced liver and kidney injury. Furthermore, SCE inhibited the upward trend of dUDP and CDP-ethanolamine in the urine of CsA rats, pathways of which are involved in pyrimidine and glycerophospholipid metabolism. We finally confirmed that this protection of SCE was regulated by the activation of Nrf2 signaling pathway and the inhibition of apoptosis. In summary, our findings indicated that SCE may effectively prevent and treat hepatorenal toxicity caused by CsA. In addition, metabolomic techniques identified potential biomarkers for the occurrence of hepatorenal toxicity in CsA rats.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Drugs, Chinese Herbal , Schisandra , Animals , Cyclosporine/toxicity , Drugs, Chinese Herbal/pharmacology , Ions , Kidney/drug effects , Liver/drug effects , NF-E2-Related Factor 2 , Rats , Schisandra/chemistry , Signal TransductionABSTRACT
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of severe visual deficits and blindness. Meanwhile, there is convincing evidence implicating oxidative stress, inflammation, and neovascularization in the onset and progression of AMD. Several studies have identified berberine hydrochloride and chrysophanol as potential treatments for ocular diseases based on their antioxidative, antiangiogenic, and anti-inflammatory effects. Unfortunately, their poor stability and bioavailability have limited their application. In order to overcome these disadvantages, we prepared a compound liposome system that can entrap these drugs simultaneously using the third polyamidoamine dendrimer (PAMAM G3.0) as a carrier. RESULTS: PAMAM G3.0-coated compound liposomes exhibited appreciable cellular permeability in human corneal epithelial cells and enhanced bio-adhesion on rabbit corneal epithelium. Moreover, coated liposomes greatly improved BBH bioavailability. Further, coated liposomes exhibited obviously protective effects in human retinal pigment epithelial cells and rat retinas after photooxidative retinal injury. Finally, administration of P-CBLs showed no sign of side effects on ocular surface structure in rabbits model. CONCLUSIONS: The PAMAM G3.0-liposome system thus displayed a potential use for treating various ocular diseases.
