ABSTRACT
To elucidate the mechanism[s] of splenic toxicity of methotrexate [MTX] and the possible protective effect of bone-marrow-derived MSCs [BM-MSCs] and adipose-derived MSCs [AD-MSCs], male Sprague-Dawley rats were given MTX orally in a dose 14 mg/kg, as a single dose/week for 2 consecutive weeks, control rats received the vehicle only, while groups 3 and 4 were intraperitoneal injected with 2 x 10[6] cells in 500 micro L phosphate buffer saline [PBS]/rat of BM-MSCs and AD-MSCs, respectively, 2 weeks after the last dose of MTX. The last group was treated with Dex [0.5 mg/kg, p.o] for 7 days starting after the last dose of MTX. Methotrexate administration showed a significant increase in spleen lipid peroxidation and nitric oxide [NO] accompanied with a significant decrease in reduced glutathione [GSH]. Microscopically, MTX induced degenerative changes in spleen tissue manifested by lymphocytic necrosis and apoptosis also MTX enhanced the splenic caspase-3 and nuclear factor-kappa B expression. The present study discloses that pretreatment with BM-MSCs or AD-MSCs protected the spleen against the oxidative stress and their splenoprotection is also linked to their anti-inflammatory and antiapoptotic properties