Doxorubicin (DOX) is an anthracycline antibiotic and a quinone-containing
chemotherapeutic drug used for various types of cancers. However, as with most anticancer
drugs, it causes many toxic effects, one of them is cognitive impairment. The present study
investigated the prophylactic and ameliorative effect of n-acetylcysteine (NAC) against DOXinduced
neurotoxicity in rats. Rats were divided into four groups. Control group: rats received
saline. NAC treated group: rats received NAC (100 mg/kg, p.o.) daily for 35 days. DOX-treated
group: rats received DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. DOX+NAC
treated group 1: rats received NAC (100 mg/kg, p.o.) daily for 35 days and DOX (4 mg/kg, i.p.)
for four weeks on day 7, 14, 21 and 28). DOX+NAC treated group 2: rats received NAC (100
mg/kg, p.o.) daily started at the 7th day of the experiment till the end of the experiment and DOX
(4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. The present results showed a significant
reduction in the body weight, which was associated with a significant increase in brain to
body weight ratio in DOX-treated rats. Tumor necrosis factor (TNF-α) level, malondialdehyde
(MDA) and total protein levels were significantly elevated. Whilst, reduced glutathione (GSH)
and glutathione peroxidase (GPx) levels were significantly decreased. Moreover, there were
histopathological abnormalities in the brain tissue of DOX-treated rats, as most of the neurons
degenerated and the blood vessels surrounded with wide perivascular spaces. In addition, the
neuropil was vacuolated. The present study demonstrated that NAC has a neuroprotective
effect on the brain damage induced by DOX, through inhibition of inflammation and oxidative
stress. This neuroprotective effect was more pronounced in DOX+NAC treated group 1, as it
produced a significant increase in brain GSH and GPx levels and more improvement in the
histopathological abnormality compared to DOX+NAC treated group 2.