Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant
tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity.
The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties.
The purpose of our study was to investigate the underlying molecular mechanisms for the potential
protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as
follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX
(DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that
DOX administration caused marked histological alterations of widespread inflammation and tubular
degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65
(NF-B/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated
lipocalin (NGAL), interleukin-1beta (IL-1 ), 8-hydroxy-20 -deoxyguanosine (8-OHdG), and Beclin-1
in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in
the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly |
