Journal Article

Camel Milk Mitigates Cyclosporine-Induced Renal Damage in Rats: Targeting p38/ERK/JNK MAPKs, NF-κB, and Matrix Metalloproteinases

Kabel, Ahmed M., Arafa, El-Shaimaa A., Alqarni, Abdulmalik M., Ashour, Ahmed M., Arab, Hany H.

2021

Overview

Renal damage is a devastating adverse effect for cyclosporine; a widely used immunosuppressant drug. The present work examined the potential of camel milk, a natural agent with marked anti-inflammatory/antioxidant properties, to attenuate cyclosporine-induced renal injury. The kidney tissue was examined with the aid of Western blotting, immunohistochemistry, biochemical assays, including colorimetric and ELISA kits. The present findings revealed that camel milk (10 mL/kg/day; for 3 weeks by gavage) significantly lowered serum creatinine, BUN, and KIM-1 renal dysfunction markers. Mechanistically, camel milk inhibited renal inflammation, as seen by significant decrease of the pro-inflammatory cytokines (MCP-1, TNF-α, IL-1β, and IL-18) and extracellular degradation signals (MMP-2 and MMP-9) and enhanced the generation of the anti-inflammatory IL-10. Moreover, it inhibited the upstream pro-inflammatory p38/ERK/JNK MAPK pathway by lowering the phosphorylation of the 3 subfamilies of MAPKs (p38 MAPK, JNK1/2, and ERK1/2). Furthermore, camel milk curbed the NF-κB pathway activation by downregulating the protein expression of activated NF-κBp65, p-NF-κBp65, and p-IκBα proteins. Additionally, camel milk inhibited renal oxidative stress by lowering the MPO activity and augmenting the reduced/oxidized glutathione ratio and total antioxidant capacity. These findings propose that camel milk may be a promising agent that inhibits cyclosporine-triggered renal inflammation via curtailing the p38/ERK/JNK MAPK and NF-κB pathways, matrix metalloproteinases, and pro-inflammatory cytokines.

• Publisher: MDPI AG,MDPI
• Subject: adverse effects / antioxidant activity / Antioxidants / Autoimmune diseases / blood serum / camel milk / Camel's milk / Colorimetry / Creatinine / cyclosporine / Cyclosporins / Cytokines / Degradation / Diabetes / Enzyme-linked immunosorbent assay / Extracellular signal-regulated kinase / Gelatinase A / Gelatinase B / Glutathione / Human subjects / Immunohistochemistry / Inflammation / Interleukin 1 / Interleukin 10 / Interleukin 18 / Kidneys / Kinases / Laboratory animals / MAP kinase / MAPK / Matrix metalloproteinase / metalloproteinases / Milk / mitogen-activated protein kinase / Monocyte chemoattractant protein 1 / NF-κB / NF-κB protein / oxidative stress / Pathogenesis / phosphorylation / protein synthesis / Proteins / Renal function / Rheumatoid arthritis / Side effects / Transplants & implants / Tumor necrosis factor-TNF / Western blotting