Details

Autor(en) / Beteiligte

• Ibrahim, Kamilia M.
• Mantawy, Eman M.
• Elanany, Mona M.
• Abdelgawad, Hend S.
• Khalifa, Nuha M.
• Hussien, Rada H.
• El-Agroudy, Nermeen N.
• El-demerdash, Ebtehal

Titel

Protection from doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles

Ist Teil von

• Naunyn-Schmiedeberg's archives of pharmacology, 2020-04, Vol.393 (4), p.739-748

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• This study was performed to examine whether clindamycin could protect against doxorubicin (DOX)-induced acute nephrotoxicity, and if so, what molecular mechanisms responsible for this protective effect. Male albino rats were pretreated with clindamycin once per day for 5 consecutive days at a dose of 300 mg/kg, i.p, then received a single dose of DOX (15 mg/kg; i.p) on the 5th day. DOX-induced marked renal injury as indicated by the presence of inflammatory cell infiltration, congestion, and edema accompanied by elevation in serum levels of creatinine and urea. These effects were alleviated by clindamycin pretreatment. DOX caused glutathione depletion and reduction in level of the antioxidant enzyme, catalase. Pretreatment with clindamycin markedly prohibited DOX-induced oxidative damage in renal tissue. Moreover, DOX provoked inflammatory responses in renal tissues as confirmed by increased expressions of NF-κB and COX-2 which were significantly reduced by clindamycin pretreatment. Besides, DOX-triggered apoptotic cascades in renal tissues as evidenced by elevated expression of pro-apoptotic proteins; Bax and cytochrome c, enhancing activity of caspase-3 enzyme whereas reducing the expression of anti-apoptotic Bcl-2 protein. Clindamycin pretreatment counteracts these apoptotic effects of DOX. Summarily, our results provide an evidence for the first time that clindamycin has a potential protective action against DOX-induced acute nephrotoxicity through inhibiting oxidative stress, inflammatory cascades, and apoptotic tissue injury.