Protective Effects of Berberine on Bortezomib-Induced Hepatorenal Toxicity in Sprague Dawley Rats: Biochemical, Molecular and Histological Evaluation.

This study investigated the potential of herbal-derived berberine (BBR) to reduce hepatorenal toxicity induced by the proteasome inhibitor bortezomib (BTZ) in male Sprague-Dawley rats. For this purpose, after BTZ and BBR administration to rats, oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis markers in liver and kidney tissues were analyzed by biochemical, qRT-PCR and ELISA methods. Moreover, to serum biochemistry analyses, histopathological and immunohistochemical examinations were performed on tissues. The data obtained showed that BBR alleviated the oxidative stress induced by BTZ in liver and kidney tissues. Additionally, ER stress markers upregulated by BTZ were suppressed by BBR. In liver and kidney tissues, inflammatory genes NF-κB, TLR-4, TNF-α, IL-1β and apoptotic genes P53, Apaf-1, Bax, Casp-3, Casp-6 and Casp-9 were triggered by BTZ administration, while BBR suppressed these genes. In immunohistochemical examinations, 8-OHdG stains in liver tissue and KIM-1 stains in kidney tissue increased with BTZ administration and decreased after BBR administration. Histopathological examinations showed that BTZ negatively affected the liver and kidney architecture, while tissue recovery occurred after BBR treatment. The improvement of the integrity of the damaged liver and kidney tissues with BBR treatment was also confirmed by the results of ALT, AST, Urea and creatinine. As a result, it was observed in the study that BTZ caused toxicity in liver and kidney tissues and may cause dysfunction in the tissues, while BBR may have a protective feature in this BTZ-induced toxicity.