肾毒性
药理学
波多辛
下调和上调
姜黄素
脂多糖
氧化应激
医学
肾
化学
内科学
足细胞
生物化学
蛋白尿
基因
作者
Iman H. Hasan,Abdulhalim A. Badr,Hassan Al‐Malki,Alanoud M. AlHindi,Hesham I. Mostafa
出处
期刊:Life Sciences
[Elsevier]
日期:2023-10-01
卷期号:330: 121996-121996
被引量:1
标识
DOI:10.1016/j.lfs.2023.121996
摘要
Sepsis is a common cause of acute kidney injury (AKI). Lipopolysaccharides (LPS) are the main gram-negative bacterial cell wall component with a well-documented inflammatory impact. Diclofenac (DIC) is a non-steroidal anti-inflammatory drug with a potential nephrotoxic effect. Curcumin (CUR) and silymarin (SY) are natural products with a wide range of pharmacological activities, including antioxidant and anti-inflammatory ones. The objective of this study was to examine the protective impact of CUR and SY against kidney damage induced by LPS/DIC co-exposure.Four groups of rats were used; control; LPS/DIC, LPS/DIC + CUR, and LPS/DIC + SY group. LPS/DIC combination induced renal injury at an LPS dose much lower than a nephrotoxic one.Nephrotoxicity was confirmed by histopathological examination and significant elevation of renal function markers. LPS/DIC induced oxidative stress in renal tissues, evidenced by decreasing reduced glutathione and superoxide dismutase, and increasing lipid peroxidation. Inflammatory response of LPS/DIC was associated with a significant increase of renal IL-1β and TNF-α. Treatment with either CUR or SY shifted measured parameters to the opposite side. Moreover, LPS/DIC exposure was associated with upregulation of mTOR and endoplasmic reticulum stress protein (CHOP) and downregulation of podocin These effects were accompanied by reduced gene expression of cystatin C and KIM-1. CUR and SY ameliorated LPS/DIC effect on the aforementioned genes and protein significantly.This study confirms the potential nephrotoxicity; mechanisms include upregulation of mTOR, CHOP, cystatin C, and KIM-1 and downregulation of podocin. Moreover, both CUR and SY are promising nephroprotective products against LPS/DIC co-exposure.
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