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. Author manuscript; available in PMC: 2019 Nov 7.
Published in final edited form as: Pharm Res. 2018 Nov 7;36(1):3. doi: 10.1007/s11095-018-2541-z

Figure 6: Chemical depletion of macrophages leads to signs of toxicity in animals fed CFZ.

Figure 6:

A, B) Daily mouse body mass and temperature taken during final week of liposome injection. C, D) Box plot of mouse body weight and temperature taken on final day of experiment. (*=p<0.001, ANOVA, Tukey’s HSD). E) Macroscopic images of livers removed from mice treated with PBS or clodronate liposomes, fed either a control or supplemented diet. The clodronate CFZ fed livers showed signs of necrosis upon gross examination. F) H&E staining of liver sections from macrophage-depleted and healthy animals. The clodronate-CFZ treated livers showed signs of necrosis radiating outward from the hepatic portal vein, while the PBS-CFZ treated mice only showed minor inflammation localized to the granulomatous areas. Scale bar is 100 um. G) TUNEL staining of liver cryosections from clodronate experiments. Apoptosis in the PBS-CFZ treated groups was localized primarily to the granulomatous regions, while the necrotic, clodronate-CFZ livers showed reduced apoptosis within the granuloma and elevated apoptosis in small, localized regions of the liver, consistent with the previously observed necrosis. Scale bar is 25 um. H) Immuno-histochemical staining for cellular replication marker Ki67 within liver sections. Granulomatous regions of PBS-CFZ treated livers showed significantly elevated cellular replication compared to the granulomas of the clodronate-CFZ treated livers. Scale bar is 200 um.