1). In addition, positive staining with anti-GSTP antibodies was observed in smooth muscle of small intestine, stomach, Tofacitinib Citrate cost and urinary bladder, as well as in hepatocytes (Fig. 1). The GST activity with CDNB or EA in tissue homogenates of GSTP-null mice was significantly lower compared with WT mice, indicating that GSTP represents a significant fraction of total GST activity in these tissues (Fig. 1, P and Q). Immunological staining intensity for GSTP was predictive of the tissue EA activity and thus supported the specific relationship between total immunoreactive GSTP protein and EA activity (Fig. 1). For example, the most intense staining with anti-GSTP antibody was in the small intestine and urinary bladder, and these organs also had the highest specific EA activity, whereas the limited, focal GSTP staining in kidney and lung was associated with the lowest tissue EA activity (Fig.
1Q). In contrast to previous work (Henderson et al., 1998), both CDNB and EA activities were significantly lower in the liver of GSTP-null mice compared with WT mice (Fig. 1P). Moreover, there was no evidence of a compensatory increase in GSTA or GSTM expression in urinary bladder of GSTP-null mice (Fig. 1O). It is interesting to note that GSTM protein was noticeably abundant in the urinary bladder. It is likely that GSTM is a major contributor of total CDNB activity in the bladder, which was equivalent of total hepatic GST activity (Fig. 1P). Fig. 1. Organ distribution of GSTP1/P2 protein and activity.
Photomicrographs of sections obtained from kidney (A, WT; B, GSTP-null), liver (C, WT; D, GSTP-null), lung (E, WT; F, GSTP-null), small intestine (G, WT; H, GSTP-null), stomach (I, WT; J, GSTP-null), … Hemorrhagic Cystitis of CY. Treatment of WT or GSTP-null mice with CY led to a significant increase in the wet weight/body weight ratio of the bladder 4 and 24 h post-treatment. However, twenty-four hours after treatment, the increase in urinary bladder wet weight/body weight ratio was significantly greater in GSTP-null than in WT mice (Fig. 2A). H&E-stained Batimastat cross-sections showed exfoliation of urothelium and edematous expansion and hemorrhage of the lamina propria layer consistent with increased wet weight of the bladder in both WT and null mice at 4 and 24 h after CY treatment (Fig. 2B). Four hours after CY treatment, epithelial exfoliation, hemorrhage, and disintegration of lamina propria appeared more severe in GSTP-null mice than in treated WT mice (Fig. 2C; Table 1). Treatment with CY significantly enhanced lamina propria area from <25% of cross-sectional area in untreated mice to >50% in both WT and GSTP-null mice (Fig. 2D).