(A–B) Minocycline suppresses PARP-1 activity in vivo and in vitro. (A) PARP-1 activity in small-intestine tissues of mice treated with 5-FU was suppressed by minocycline administration. PARP-1 activity was identified by anti-PAR immunohistochemical staining. Mice were sacrificed on day 5 and PAR was stained in ileal histological sections. Red arrows represent anti-PAR positive enterocytes (original magnification 400×). (B) Minocycline administration suppressed the upregulation of PARP-1 activity induced by 5-FU in IEC-6 cells. Red arrows indicate positive
EQKLISEEDL (original magnification 200×). (C–D) Effects of minocycline on proliferation and apoptosis of enterocytes in the small intestines of mice with 5-FU-induced intestinal mucositis. The apoptotic index (C) was defined as the average number of TUNEL-positive enterocytes per field in 5–6 continuous microscopic fields at 400× magnification in sections of distal ileal tissue from mice sacrificed on day 5 after 5-FU treatment (n = 3/group). The proliferation index (D) was defined as the average number of PCNA-positive
cells per crypt in 6–9 different microscopic fields at 400× magnification in sections of ileum (n = 3/group). Each bar represents the mean ± SEM; ??P