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Salas-Silva, Soraya; Lopez-Ramirez, Jocelyn; Barrera-Chimal, Jonatan; Lazzarini-Lechuga, Roberto; Simoni-Nieves, Arturo; Souza, Veronica; Miranda-Labra, Roxana U; Masso, Felipe; Roma, Marcelo G; Gutierrez-Ruiz, Maria Concepcion; Bucio-Ortiz, Leticia E; Gomez-Quiroz, Luis (2022)

HEPATOCYTE GROWTH FACTOR REVERSES CHOLEMIC NEPHROPATHY ASSOCIATED WITH ALPHA-NAPHTHYLISOTHIOCYANATE-INDUCED CHOLESTASIS IN MICE

Life Sci 295():
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Hepatocyte growth factor (HGF) has been proved to protect the liver against α-naphthylisothiocyanate (ANIT)-induced cholestasis by acting as an antioxidant agent and redirecting toxic biliary solutes towards blood for urinary excretion. However, this may represent an additional potential risk for kidney integrity, which is already compromised by the cholestatic process itself (cholemic nephropathy). Therefore, in the present work, we studied the renal damage caused by ANIT-induced cholestasis and whether it is aggravated or, on the contrary, counteracted by HGF; if the latter holds, the involvement of its antioxidant properties will be ascertained. ANIT-induced cholestatic deleterious renal effects were corroborated by the presence of urine bile salts, impairment of renal function, and the alterations of renal damage markers, such as HSP72, creatinine clearance, and albuminuria. HGF fully reverted all these, and the cast formation in the tubules was significantly decreased. These findings were associated with the control of renal oxidative stress. In summary, despite HGF enhancing the overload of potentially harmful biliary constituents that the kidney should remove from the bloodstream as an alternative depuration organ in cholestasis, it simultaneously protects the kidney from this damage by counteracting the prooxidant effects resulting from this harmful exposure.