A Tripeptide (Ser-Arg-Pro, SRP) from <i>Sipunculus nudus</i> L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice
Yanmei Pan,
Zhilan Peng,
Zhijia Fang,
Lukman Iddrisu,
Lijun Sun,
Qi Deng,
Ravi Gooneratne
Affiliations
Yanmei Pan
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Zhilan Peng
School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang 524023, China
Zhijia Fang
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Lukman Iddrisu
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Lijun Sun
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Qi Deng
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Ravi Gooneratne
Department of Wine, Food and Molecular Biosciences, Lincoln University, Lincoln 7647, New Zealand
Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from Sipunculus nudus L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1β, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.
