LAUSR

The lymphatic organ, the spleen, is of immense immunological importance as it is the largest blood filter in the mammalian system. The objective of the current study is to explore the detrimental cellular and sub-cellular effects in the spleen, mediated by the widely used herbicide, paraquat (PQ). PQ is an uncoupling agent for the electron transport chain complex in the mitochondria, which promulgates serious alterations in the intracellular oxidative microenvironment. This leads to the activation of a cascade of sub cellular events leading to cell death. Since PQ-induced oxidative damage in the spleen is not well explored, we planned to develop a PQ toxicity model in rodents, addressing its negative effects in the highest molecular terms. The toxicity markers were evaluated in terms of oxidative stress, cellular apoptosis, inflammation and splenomegaly in Swiss albino mice after treatment with PQ. The increase in thiobarbituric acid reactive substances (TBARS), tissue nitrite formation, intracellular reactive oxygen species (iROS) production, depletion of the activities of catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and the reduction in mitochondrial inner trans membrane potential (MMP) were significant in the PQ treated group compared to the control. A pronounced inhibition of cell proliferative response and increased p53, Bax expression, caspase 3 activities and decreased Bcl-2 were also associated with PQ-induced apoptosis. Moreover, a pro-inflammatory response was apparent in the PQ treated group as indicated by elevated levels of pro-inflammatory markers (TNF-α, IL-6 and COX-2). Thus, this is perhaps the first mechanistic report showing how a herbicide induces the oxidative stress responsible for immunomodulation, apoptosis, as well as splenomegaly in the murine system.