Protective Effects of Low-Dose Alcohol against Acute Stress-Induced Renal Injury in Rats: Involvement of CYP4A/20-HETE and LTB(4)/BLT1 Pathways.
Protective Effects of Low-Dose Alcohol against Acute Stress-Induced Renal Injury in Rats: Involvement of CYP4A/20-HETE and LTB(4)/BLT1 Pathways.
复制标题
低剂量酒精对大鼠急性应激性肾损伤的保护作用：CYP4A/20-HETE 和 LTB 4/BLT1 通路的参与
DOI：
10.1155/2021/4475968
复制
发表时间：
2021
影响因子：
--
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Chen Y;Yang H;Yang T;Zhang H;Zhao Y;Li L;Fan H
Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test. Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key indicators of the cytochrome P450 (CYP) 4A1/20-hydroxystilbenetetraenoic acid (20-HETE) pathway, cyclooxygenase (COX)/prostaglandin E2 (PGE2) pathway, and leukotriene B4 (LTB4)/leukotriene B4 receptor 1 (BLT1) pathway were measured by real-time PCR and ELISA. We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels (P < 0.05). Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression and reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive cells (P < 0.01). Correlation analysis indicated that 20-HETE was strongly correlated with oxidative stress, while LTB4 was strongly correlated with inflammation. Low-dose alcohol inhibited AS-induced increases in CYP4A1, CYP4A2, CYP4A3, CYP4A8, and BLT1 mRNA levels and LTB4 and 20-HETE content (P < 0.01). Interestingly, low-dose alcohol had no effect on COX1 or COX2 mRNA expression or the concentration of PGE2. Furthermore, low-dose alcohol reduced calcium-independent phospholipase A2 mRNA expression, but did not affect secreted phospholipase A2 or cytosolic phospholipase A2 mRNA expression. Together, these results indicate that low-dose alcohol ameliorated AS-induced renal injury by inhibiting CYP4A/20-HETE and LTB4/BLT1 pathways, but not the COX/PGE2 pathway.
登录
查看更多内容
右美托咪定通过抑制 ROS/JNK 信号通路减轻氧化应激和细胞凋亡，从而改善急性应激性肾损伤
影响因子：
--
作者：
Chen Y;Feng X;Hu X;Sha J;Li B;Zhang H;Fan H
通讯作者：
Fan H
影响因子：
1.9
作者：
Alinaghipour, Azam;Mazoochi, Tahereh;Ardjmand, Abolfazl
通讯作者：
Ardjmand, Abolfazl
影响因子：
2.4
作者：
LAMBERT, IH;HOFFMANN, EK;CHRISTENSEN, P
通讯作者：
CHRISTENSEN, P
影响因子：
3.7
作者：
Eid S;Maalouf R;Jaffa AA;Nassif J;Hamdy A;Rashid A;Ziyadeh FN;Eid AA
通讯作者：
Eid AA
影响因子：
2.1
作者：
Amin, Shaimaa Nasr;El-Aidi, Ahmed Amro;Hassan, Sherif Sabry
通讯作者：
Hassan, Sherif Sabry