N-(2-hydroxy phenyl) acetamide ameliorate inflammation and doxorubicin-induced nephrotoxicity in rats

Abstract

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.