ACE2/ACE imbalance mediates bisphenol A-induced lung injury in Wistar rats: Results from captopril versus losartan histo-biochemical study.

Bisphenol-A (BPA) is a synthetic chemical compound broadly used in the plastic and epoxy resin industries with a considerable potential for food contamination. Literary reports have suggested that the altered renin-angiotensin system (RAS) is a mechanism for lung injury and inflammation caused by variable agents. The current study sought to investigate the contribution of RAS to BPA-induced lung damage. Moreover, the study assessed whether angiotensin II and/or bradykinin pathways were involved. For this aim, the angiotensin-converting enzyme (ACE) inhibitor captopril (Cap), either alone or combined with bradykinin receptor antagonist icatibant (Icat), was attempted versus the angiotensin receptor blocker losartan (Los). An eight-week study was conducted on forty Wistar male albino rats randomly divided into five equal groups: control, BPA, BPA/Cap, BPA/Los, and BPA/Cap/Icat groups. Captopril (100 mg/mL) and losartan (200 mg/mL) were given orally in drinking water, but icatibant (Icat) was injected subcutaneously (250 µg/kg) during the last two weeks of captopril treatment. Biochemical analysis of bronchoalveolar lavage fluid (BALF) and lung tissues, polymerase chain reaction (PCR) assay for ACE, ACE2, and caspase-3 genes expression, and histological and immunohistochemical studies were carried out to evaluate BPA-mediated pulmonary inflammation/apoptosis. BPA impaired the histological structure of the lungs, increased ACE, ACE2, and caspase-3 expressions at both gene/protein levels, and increased BALF inflammatory cytokines and lung oxidative markers. Inhibiting the ACE activity by captopril maintained the histological lung injury score, restored inflammation and the ACE2/ACE balance, and decreased apoptosis. Further improvement was obtained by the angiotensin II receptor (ATR1) blocker losartan. Icatibant (bradykinin B2 receptor blocker) didn't counteract the observed captopril effects. It was strongly suggested that RAS contributed to BPA-induced lung damage via alteration of ACE2 and ACE expression mediating angiotensin II generation rather than bradykinin.

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol-A versus dibutyl phthalate is mediated by HSP60/caspase-3 expression in male albino rats.

Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products. Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylin & eosin (H & E) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by H & E changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction. However, rats exposed to DBP alone showed no changes in either α or ß-cells. Both combined-exposed animals displayed α and ß apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in α-cell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/ß cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.