N-(2-hydroxy phenyl) acetamide ameliorate inflammation and doxorubicin-induced nephrotoxicity in rats.
International immunopharmacology(2023)
摘要
Doxorubicin (DOX) is an anthracyclin antibiotic used for the treatment of various cancers. Nephrotoxicity is among the serious side effects of DOX, therefore, DOX-induced nephrotoxic model has been widely used to study nephropathies. The objectives of this study is to investigate the possible anti-inflammatory and nephroprotective effects of salicylic acid derivative, N-(2-hydroxy phenyl) acetamide (NA-2), in a rat model of DOX-induced nephrotoxicity. The in vitro anti-inflammatory potential of NA-2 was manifested by whole blood oxidative burst and nitric oxide (NO) assays with no toxicity on normal human fibroblast (BJ) cells, human embryonic kidney (HEK-293) cells, and normal monkey kidney epithelial (Vero) cells. The in vivo study included five groups: Normal control, DOX (6 mg/kg DOX-i.v.via tail vein), NA-2 treated control-i.p., NA-2/DOX treated-i.p., and prednisolone/DOX treated. After 7 days of DOX administration, rats with urinary protein level of >50 mg/kg/day were selected. Treatment group rats received i.p. doses of NA-2 (10 mg/kg/day) for 3 weeks with weekly monitoring of urinary protein excretion and body weights. mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and kidney injury molecule (KIM)-1 was analyzed by quantitative polymerase chain reaction (qPCR). Protein expressions were analyzed by immunohistochemistry. NA-2 attenuated DOX-induced changes in serum and urine levels, and improved inflammatory profile of the renal tissue. Histopathological findings revealed protective effects of NA-2 showing lesser lesions. We conclude that NA-2 is able to protect against DOX-induced renal damage functionally, biochemically and histopathologically with corresponding improvement in the kidney inflammatory profile.
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