BACTERIAL LIPOPOLYSACCHARIDE INDUCES A ‘DOUBLE HIT’ WITH DIFFERENTIAL EFFECTS CENTRALLY AND PERIPHERALLY IN A DIETHYLNITROSAMINE-TREATED WISTAR RAT MODEL OF HEPATIC CANCER

Bio behavioural aspects, immunity, and disease course are interlinked in a majority of conditions, particularly cancer. Peripheral stressors or their products regulate immunity by various ways. When there is added insult in an already compromised immune state such as cancer, as is done here using lipopolysaccharide (LPS), the system is said to be ‘double-hit. Behavioural and brain tissue-associated biochemical changes on LPS challenge have been assayed in a Diethylnitrosamine (DEN)-treated Wistar rat model of hepatic cancer. Peripheral and central effects of LPS challenge have been screened at levels of neuro behaviours, liver enzymes and brain enzymes. While LPS challenge reduced exploratory and grooming behaviours across groups after 2 h, the effect disappeared on testing after 4 h, 6 h post LPS injection, rats demonstrated increased open arm time, reduced closed arm time and increased entries into both arms of the elevated plus-maze. DEN treatment induced similar results. LPS challenge in DEN-treated rats however, led to reduced open arm time, increased closed-arm time, and reduced entries into both arms. LPS challenge reduced locomotion in DEN-treated rats, an effect not observed in controls. DEN treatment induced a reduction in brain AChE that was similar also on LPS challenge. There was a concomitant increase in nNOS in the DEN-treated group, with nNOS not affected by LPS challenge. Central and peripheral effects on antioxidants and lipid peroxidation as a result of DEN treatment and LPS challenge were observed. Results indicate that neuro behaviours, the activity of brain and liver tissue enzymes vary in cancer-induced, altered immune states.