A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice.
Yanmei PanZhilan PengZhijia FangLukman IddrisuLijun SunQi DengRavi GooneratnePublished in: Marine drugs (2024)
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.
Keyphrases
- oxidative stress
- acute kidney injury
- diabetic rats
- induced apoptosis
- signaling pathway
- cell death
- cardiac surgery
- heavy metals
- cell cycle arrest
- pi k akt
- endoplasmic reticulum stress
- inflammatory response
- dna damage
- ischemia reperfusion injury
- high glucose
- nk cells
- cell proliferation
- protein kinase
- lipopolysaccharide induced
- risk assessment
- skeletal muscle
- smoking cessation
- insulin resistance
- network analysis
- heat stress
- case control