Caspase 3 role and immunohistochemical expression in assessment of apoptosis as a feature of H1N1 vaccine-caused Drug-Induced Liver Injury (DILI)

BACKGROUND Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS This 2014's experimental study was conducted on 70 albino rats. They were given ArepanrixTM H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1st and 2nd doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2nd dose, mix2 and mix4 injected with 1st and 2nd doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2nd dose. Histopathological evaluation and histochemical assessment of metabolic protein, glycogen and collagen changes using PAS, bromophenol blue, Mallory's trichrome and immunohistochemistry for caspase 3 on liver tissue paraffin sections were done. Image analysis system Leica QIIN 500 was used. Data were analyzed by SPSS software, using descriptive statistics and ANOVA. RESULTS Histopathological changes ranging from subtle up to necrosis were noticed, mainly in mix groups. Metabolic protein and glycogen changes were the maximum in mix5 group (p<0.01). Collagen deposition in sinusoids was higher in mix groups, and maximally in vac5 and mix5. Apoptotic hepatocytes expressing diffuse strong nuclear and cytoplasmic caspase 3 were the highest in mix5. CONCLUSION H1N1 vaccine can cause DILI by either direct toxic or idiosyncratic metabolic type reactions rather than immunologic hypersensitivity type. It ranges from subtle changes up to necrosis. Caspase 3 is pivotal in liver damage etiology, apoptosis induction and processing. Follow up for at least 2 months after the 2nd dose of H1N1 vaccine is recommended to rule out H1N1-induced DILI.