Betulinic acid abates N-nitrosodimethylamine-induced changes in lipid metabolism, oxidative stress, and inflammation in the liver and kidney of Wistar rats
Betulinic acid abates N-nitrosodimethylamine-induced changes in lipid metabolism, oxidative stress, and inflammation in the liver and kidney of Wistar rats
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DOI：
10.1002/jbt.22901
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发表时间：
2021-09-02
影响因子：
3.6
通讯作者：
Adaramoye, Oluwatosin A.
中科院分区：
文献类型：
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作者：
Adeleke, Gbadebo E.;Adaramoye, Oluwatosin A.
N-亚硝胺与人类癌症有关，因为它们存在于饮用水和饮食中。本研究评估桦木酸（BA）在减轻N-亚硝基二甲胺（NDMA）处理的大鼠的氧化应激、炎症和高脂血症中的作用。将24只雄性大鼠平均分为4组。I组为对照组，II组为BA（25 mg/kg）组，III组为NDMA（5 mg/kg）组，IV组为BA（25 mg/kg）+NDMA（5 mg/kg）组。结果显示，相对于对照，施用NDMA显著（p < 0.05）升高了肝脏和肾脏中的丙二醛。NDMA处理显著降低了肝脏和肾脏中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶的活性（p < 0.05），而BA处理则提高了这些酶的活性。BA降低血清白细胞介素-6和肿瘤坏死因子-α水平对抗NDMA效应。此外，NDMA增加肝脏和肾脏甘油三酯，而磷脂水平降低。NDMA显着调制的药物代谢酶（苯胺羟化酶，氨基比林-N-脱甲基酶，尿苷二磷酸葡萄糖醛酸转移酶）的活动，而BA能够恢复这些酶的值接近控制。组织学显示，在NDMA给药大鼠中，肝脏中存在浸润和纤维增生，而肾脏中观察到皮质变性。这些病变在用BA处理的NDMA大鼠中减少。研究结果表明，BA通过与抗氧化、抗炎和降脂途径相关的反应改善了NMDA诱导的大鼠肝脏和肾脏损伤。
N-nitrosamines have been linked with cancer in humans due to their presence in drinking water and diets. This study evaluated the role of betulinic acid (BA) in abating oxidative stress, inflammation, and hyperlipidemia in rats treated with N-nitrosodimethylamine (NDMA). Twenty-four male rats were assigned into four equal groups. Group I served as the control, Group II received BA (25 mg/kg), Group III received NDMA (5 mg/kg) and, Group IV received BA (25 mg/kg) and NDMA (5 mg/kg). Results showed that the administration of NDMA significantly (p < 0.05) elevated malondialdehyde in the liver and kidney relative to controls. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and the level of glutathione were significantly (p < 0.05) decreased by NDMA, while treatment with BA elevated the activities of these enzymes in the liver and kidney. The BA lowered serum interleukin-6 and tumor necrosis factor-alpha levels against the NDMA effect. Furthermore, NDMA increased hepatic and renal triglyceride while phospholipids levels were decreased. NDMA significantly modulated the activities of drug-metabolizing enzymes (aniline hydroxylase, aminopyrine-N-demethylase, and uridyldiphosphoglucuronyltransferase), while BA was able to restore these enzymes to values close to controls. Histology revealed the presence of infiltration and fibroplasia in the liver, while cortical degeneration was noticed in the kidney in NDMA-administered rats. These lesions were reduced in the NDMA rats treated with BA. The findings suggest that BA improves NDMA-induced damage in the liver and kidney of rats through reactions that can be linked with antioxidant, anti-inflammatory, and lipid-lowering pathways.