Redox disequilibrium vis-a-vis inflammatory cascade mediation of lymphocyte dysfunction, apoptosis, cytokine expression and activation of NF-κB in subclinical diabetic goats

Abstract

Molecular basis of diabetes induced oxidative stress and immune dysfunction have not been reported in animal science. The present study envisages same in subclinical diabetic (SCD) goats (6) diagnosed on biochemical and histopathological basis in reference to non-diabetic (NSCD) goats (6). Oxidative stress indices were analyzed by manual methods. The concentration of reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) was significantly lower in SCD goats than in NSCD goats; whereas the lipid peroxide (LPO) was higher in SCD. Catalase (CAT) activity was nonsignificantly lower in SCD goats than NSCD goats. SCD goats had significantly lower lymphocyte stimulation index by cell culture and higher apoptotic cell percentage by flow cytometry than NSCD goats. The concentration of the transforming growth factor beta 1 (TGF-β1) by ELISA was significantly higher in SCD goats than in NSCD. The expressions of tumour necrosis factor alpha (TNF-α) and interleukin 8 (IL 8) by RT-PCR were higher in SCD goats than in non-diabetic ones. Expression of transcription factor (NF-κB) by western blot was significantly higher in SCD goats than NSCD goats. Fall of antioxidants (GSH, SOD, catalase) and rise of oxidants (LPO) suggest oxidative stress. Decrease of immune cell function, rise of inflammatory cytokines and transcription factors suggest immune dysfunction. Hence it was concluded that SCD induced oxidative stress and impairment of immunity in goats, which was most likely associated with depletion of antioxidants, increase of oxidants and inflammatory mediators. NF-κB, most likely have played a mediatory role in coordinating these intricate responses.