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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 4: The accumulation of insoluble aggregates and granuloma formation is dependent on the isopropyl group in the CFZ molecule.

Figure 4:

A) The derivative 568 replaces the isopropyl group with an ethyl alcohol, limiting its ability to form insoluble aggregates within the liver and does not induce granulomas as is seen in CFZ. B) H&E staining of a liver from a mouse treated with 568 shows no signs of granuloma formation. Scale bar is 200 um. C) The fluorescence of derivative 568 can be detected in the bile canaliculi of the liver, showing that the liver may be actively removing the chemical and eliminating it from the body. Scale bar is 200 um. D) Zoomed in region of the bile canaliculi showing the fluorescence of derivative 568. Scale bar is 50 um. E) Chemical structure of CFZ. F) H&E staining of CFZ treated liver shows extensive granuloma formation. G) CFZ treatment leads to insoluble aggregate and hydrochloride salt accumulation. H) Zoomed in region of CLDIs within the liver. Scale bar is 50 um. Note: Brightness for derivative 568 fluorescence images have been elevated to show biliary localization of drug.