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Article

Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis

1
Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy
2
Division of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa Largo Gaslini, 16148 Genoa, Italy
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Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy
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Department of Experimental, Diagnostic and Specialty Medicine—DIMES, “F. Addarii” Institute of Oncology and Transplant Pathology, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy
5
Department of Chemistry “G. Ciamician”, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Tatsuo Kanda and Hirayuki Enomoto
J. Clin. Med. 2022, 11(3), 636; https://doi.org/10.3390/jcm11030636
Received: 21 December 2021 / Revised: 19 January 2022 / Accepted: 23 January 2022 / Published: 27 January 2022
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl4) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl4 administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI. View Full-Text
Keywords: acute kidney injury; bile acids; choleric nephropathy; liver cirrhosis; organic transport proteins; rat model; serum inflammation biomarkers; urinary tubular injury biomarkers acute kidney injury; bile acids; choleric nephropathy; liver cirrhosis; organic transport proteins; rat model; serum inflammation biomarkers; urinary tubular injury biomarkers
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MDPI and ACS Style

Donadei, C.; Angeletti, A.; Cappuccilli, M.; Conti, M.; Conte, D.; Zappulo, F.; De Giovanni, A.; Malvi, D.; Aldini, R.; Roda, A.; La Manna, G. Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis. J. Clin. Med. 2022, 11, 636. https://doi.org/10.3390/jcm11030636

AMA Style

Donadei C, Angeletti A, Cappuccilli M, Conti M, Conte D, Zappulo F, De Giovanni A, Malvi D, Aldini R, Roda A, La Manna G. Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis. Journal of Clinical Medicine. 2022; 11(3):636. https://doi.org/10.3390/jcm11030636

Chicago/Turabian Style

Donadei, Chiara, Andrea Angeletti, Maria Cappuccilli, Massimiliano Conti, Diletta Conte, Fulvia Zappulo, Alessio De Giovanni, Deborah Malvi, Rita Aldini, Aldo Roda, and Gaetano La Manna. 2022. "Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis" Journal of Clinical Medicine 11, no. 3: 636. https://doi.org/10.3390/jcm11030636

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