Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro.
10.1007/s11655-022-3574-z
- Author:
Yan YANG
1
;
Fei-Lin GE
2
;
Xiao-Yan ZHAN
2
;
Wen-Qing MU
2
;
Zhi-Yong LI
2
;
Li LIN
2
;
Zi-Ying WEI
2
;
Zhao-Fang BAI
2
;
Qin SUN
3
;
Xiao-He XIAO
2
Author Information
1. School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan Province, 646000, China.
2. Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
3. School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan Province, 646000, China. zxyjhsq@swmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Schisandra chinensis oil;
apoptosis;
aristolochic acid I;
metabolic enzymes;
nephrotoxicity;
reactive oxygen species
- MeSH:
Animals;
Apoptosis;
Aristolochic Acids/toxicity*;
Cytochrome P-450 CYP1A1/metabolism*;
Cytochrome P-450 CYP1A2/metabolism*;
Glutathione/metabolism*;
Kidney/drug effects*;
Kidney Diseases/drug therapy*;
Mice;
Mice, Inbred C57BL;
Oxidative Stress;
Plant Oils/therapeutic use*;
Protective Agents/therapeutic use*;
Reactive Oxygen Species/metabolism*;
Schisandra;
Superoxide Dismutase/metabolism*
- From:
Chinese journal of integrative medicine
2022;28(7):603-611
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.
METHODS:C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.
RESULTS:SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).
CONCLUSIONS:SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.
