Abstract:
Bisphenol A (BPA), a weak estrogenic endocrine disruptor and a well-known plasticizer, has the potential to
perturb diverse physiological functions; however, its impact on immune and metabolic function in aquatic
vertebrates is relatively less understood. The present study aims to investigate the impact of BPA on hepato toxicity, metabolic and immune parameters vis-a-vis � estrogen receptor expression modulation in a freshwater
teleost, Labeo bata (Cyprinidae, Cypriniformes). The 96-h median lethal concentration of BPA in L. bata has been
determined as 4.79 mg/L. Our data demonstrate that congruent with induction of plasma vitellogenin (VTG),
chronic exposure to sub-lethal BPA (2 and 4 μM/L) attenuates erythrocyte count, hemoglobin concentration,
packed cell volume, mean corpuscular hemoglobin, but not leukocyte number. Further, a significant increase in
MDA, concomitant with diminished catalase and heightened GST activity corroborates well with hepatic
dystrophic changes, appearance of fatty liver (macrovesicular steatosis) and elevated serum lipids (triglyceride,
cholesterol, LDL, VLDL) in BPA-treated groups. Interestingly, a differential regulation of estrogen receptor (ER)
subtypes at transcript and protein level signifies negative influence of BPA on hepatic ERα/ERβ homeostasis in
this species. While at a lower dose it promotes Akt phosphorylation (activation), BPA at the higher dose at tenuates ERK1/2 phosphorylation (activation), suggesting potential alteration in insulin sensitivity. Importantly,
dose-dependent decrease in hepatic TNF-α, IL-1β, iNOS (NOS2) expression and nitric oxide (NO) level corre sponds well with progressive decline in p-NF-κB, p-p38 MAPK, albeit with differential sensitivity, in BPA-exposed
groups. Collectively, BPA exposure has wide-spread negative influence on hematological, biochemical and he patic events in this species
