Abstract
Purpose The goal of the current study was to clarify the potential molecular mechanism underlying the protective efects
of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of
the Kelch-like-associated protein-1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2)–heme oxygenase-1 (HO-1)
signaling pathway in minimizing the oxidative stress induced by diazinon (DZN).
Methods Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under
typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive
oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4
weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples
were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests.
Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and
histopathological examination.
Results SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative
indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of
HO-1, a crucial target enzyme of Nrf2.
Conclusions SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.
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