Copic findings.Individual cell degeneration20 (1)40 (2)????marked??20 (1) E/I ** (n = 5) ?Ballooning degeneration????Mod??Mild?????D/I* (n = 5)A/I (n = 
5)C/I (n = 5)B/I (n = 5)?F/I (n = 5)Groups?60 (3)40 (2)??Renal and Hepatic Toxicity of a Gold (III) CompoundTable 3. Sub-acute toxicity, salient renal microscopic findings.Groups (n = 6 in each group)Dosage mg/kgDeathPyelitis/interstitial inflammation Mild Mod/marked ?16.66 (1)Congestion Mild 100 (6) 100 (6) 
Mod/Marked ??A/II (n = 6) B/II (n = 6)32.20100 (6) 83.33 (5)doi:10.1371/journal.pone.0051889.tTable 4. Sub-acute toxicity, salient hepatic microscopic findings.GroupDosage mg/kgDeathBallooning degeneration Mild Moderate 16.66 (1) 16.66 (1) Marked 66.66 (4) 16.66 (1)Inflammation portal/lobular Mild 83.33 (5) 66.66 (4) Moderate ??Marked ??Congestion Mild 83.33 (5) 33.33 (2) Mod/marked 16.66 (1) 66.66 (4)A/II**/*** (n = 6) B/II (n = 6)32.2016.66 (1) 16.66 (1)**100 (6) cases revealed Salmon calcitonin web capsular inflammation. ***16.66 (1) case revealed an occasional microgranuloma. doi:10.1371/journal.pone.0051889.tThe control group (F/I) with all animals alive revealed normal renal tubular histology (Fig. 4a). Varying extent of congestion dominated the entire histopathological spectrum. Hepatic microscopic findings. The hepatic specimens of almost all 5 animals 25033180 of each group, A/I, B/I, C/I, D/I and E/Irevealed variable extent of micro and macro-vesicular steatosis (Fig. 5 and Fig. 6a). Varying extent of congestion (Fig. 6b and 6c) along with few cases showing sinusoidal obstruction syndrome were also present. In A/I and B/I, one and two cases respectively, revealed scattered individual hepatocytic cell degeneration 23115181 without inflammation. One case showing focal necrosis with inflammationFigure 2. Spectrum of renal tubular necrosis seen in acute toxicity study of a gold (III) AKT inhibitor 2 compound [Au(en)Cl2]Cl. doi:10.1371/journal.pone.0051889.gRenal and Hepatic Toxicity of a Gold (III) CompoundFigure 3. Microscopic findings of renal tubules showing different grades of renal tubular necrosis as seen in the acute toxicity study of a gold (III) compound [Au(en)Cl2]Cl. a b: Grade 2 as seen in H E 620 and 640. Necrotic tubules are seen amongst viable renal tubules. The necrosis is less than 25 of the total material examined. In 640 magnification, more abundant, necrotic cells are seen along with normal renal tubules. c d: Grade 1 as seen in H E 640 magnification. Scattered individual apoptotic/necrotic cells with strongly eosinophilic cytoplasm and pyknotic nuclei are seen. e f: Grade 5 as seen in H E 620 and 640 The entire field shows mostly necrotic renal tubules. doi:10.1371/journal.pone.0051889.gRenal and Hepatic Toxicity of a Gold (III) CompoundFigure 4. Renal and hepatic tissues in the controls used in acute (a,b,c) and sub-acute (d,e,f) toxicity parts of study. a: Renal tissue showing mild congestion with no other pathological change as seen in acute toxicity controls (H E x40). b: Hepatic tissue as seen in acute toxicity controls (H E x40) showing mild congestion. No other pathological change is seen in this focus. c: Marked ballooning degeneration as seen in acute toxicity controls (H E x40). d: Unremarkable renal tubules as seen in sub-acute toxicity controls (H E x40). e: Unremarkable hepatic tissue as seen in sub-acute toxicity controls (H E x20). f: Unremarkable hepatic tissue as seen in sub-acute toxicity controls (H E x40). doi:10.1371/journal.pone.0051889.gand another one revealin.Copic findings.Individual cell degeneration20 (1)40 (2)????marked??20 (1) E/I ** (n = 5) ?Ballooning degeneration????Mod??Mild?????D/I* (n = 5)A/I (n = 5)C/I (n = 5)B/I (n = 5)?F/I (n = 5)Groups?60 (3)40 (2)??Renal and Hepatic Toxicity of a Gold (III) CompoundTable 3. Sub-acute toxicity, salient renal microscopic findings.Groups (n = 6 in each group)Dosage mg/kgDeathPyelitis/interstitial inflammation Mild Mod/marked ?16.66 (1)Congestion Mild 100 (6) 100 (6) Mod/Marked ??A/II (n = 6) B/II (n = 6)32.20100 (6) 83.33 (5)doi:10.1371/journal.pone.0051889.tTable 4. Sub-acute toxicity, salient hepatic microscopic findings.GroupDosage mg/kgDeathBallooning degeneration Mild Moderate 16.66 (1) 16.66 (1) Marked 66.66 (4) 16.66 (1)Inflammation portal/lobular Mild 83.33 (5) 66.66 (4) Moderate ??Marked ??Congestion Mild 83.33 (5) 33.33 (2) Mod/marked 16.66 (1) 66.66 (4)A/II**/*** (n = 6) B/II (n = 6)32.2016.66 (1) 16.66 (1)**100 (6) cases revealed capsular inflammation. ***16.66 (1) case revealed an occasional microgranuloma. doi:10.1371/journal.pone.0051889.tThe control group (F/I) with all animals alive revealed normal renal tubular histology (Fig. 4a). Varying extent of congestion dominated the entire histopathological spectrum. Hepatic microscopic findings. The hepatic specimens of almost all 5 animals 25033180 of each group, A/I, B/I, C/I, D/I and E/Irevealed variable extent of micro and macro-vesicular steatosis (Fig. 5 and Fig. 6a). Varying extent of congestion (Fig. 6b and 6c) along with few cases showing sinusoidal obstruction syndrome were also present. In A/I and B/I, one and two cases respectively, revealed scattered individual hepatocytic cell degeneration 23115181 without inflammation. One case showing focal necrosis with inflammationFigure 2. Spectrum of renal tubular necrosis seen in acute toxicity study of a gold (III) compound [Au(en)Cl2]Cl. doi:10.1371/journal.pone.0051889.gRenal and Hepatic Toxicity of a Gold (III) CompoundFigure 3. Microscopic findings of renal tubules showing different grades of renal tubular necrosis as seen in the acute toxicity study of a gold (III) compound [Au(en)Cl2]Cl. a b: Grade 2 as seen in H E 620 and 640. Necrotic tubules are seen amongst viable renal tubules. The necrosis is less than 25 of the total material examined. In 640 magnification, more abundant, necrotic cells are seen along with normal renal tubules. c d: Grade 1 as seen in H E 640 magnification. Scattered individual apoptotic/necrotic cells with strongly eosinophilic cytoplasm and pyknotic nuclei are seen. e f: Grade 5 as seen in H E 620 and 640 The entire field shows mostly necrotic renal tubules. doi:10.1371/journal.pone.0051889.gRenal and Hepatic Toxicity of a Gold (III) CompoundFigure 4. Renal and hepatic tissues in the controls used in acute (a,b,c) and sub-acute (d,e,f) toxicity parts of study. a: Renal tissue showing mild congestion with no other pathological change as seen in acute toxicity controls (H E x40). b: Hepatic tissue as seen in acute toxicity controls (H E x40) showing mild congestion. No other pathological change is seen in this focus. c: Marked ballooning degeneration as seen in acute toxicity controls (H E x40). d: Unremarkable renal tubules as seen in sub-acute toxicity controls (H E x40). e: Unremarkable hepatic tissue as seen in sub-acute toxicity controls (H E x20). f: Unremarkable hepatic tissue as seen in sub-acute toxicity controls (H E x40). doi:10.1371/journal.pone.0051889.gand another one revealin.
