Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC)
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Authors: Zhang, Kai; Liu, Chuanxin; Yang, Tiange; Li, Xinxin; Wei, Longyin; Chen, Dongling; Zhou, Jiali; Yin, Yihui; Yu, Xinyu; Li, Fei
Abstract
Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.
Perinatal factors contributing to chronic kidney disease in a cohort of Japanese children with very low birth weight
PEDIATRIC NEPHROLOGY
Authors: Uemura, Osamu; Ishikura, Kenji; Kaneko, Tetsuji; Hirano, Daishi; Hamasaki, Yuko; Ogura, Masao; Mikami, Naoaki; Gotoh, Yoshimitsu; Sahashi, Takeshi; Fujita, Naoya; Yamamoto, Masaki; Hibino, Satoshi; Nakano, Masaru; Wakano, Yasuhiro; Honda, Masataka
Abstract
Background Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? Methods This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age >= 3 years. A structural equation model was used to examine the pathologic constitution. Results The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 +/- 2.6 years and mean eGFR 111.7 ml/min/1.73 m(2)at last encounter. Pathway analyses showed intrauterine malnutrition (beta= 0.85) contributed more to chronic kidney damage than stress during the neonatal period (beta= - 0.19) and prematurity (beta= 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. Conclusions IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.