Lab Anim Res.  2016 Dec;32(4):200-207. 10.5625/lar.2016.32.4.200.

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats

• Shin JY
• Han JH
• Ko JW
• Park SH
• Shin NR
• Jung TY
• Kim HA
• Kim SH
• Shin IS
• Kim JC

• KMID: 2362911
• DOI: http://doi.org/10.5625/lar.2016.32.4.200

Abstract

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

Keyword

Acetaminophen; nephrotoxicity; KIM-1; NGAL; diallyl disulfide; protective effect

MeSH Terms

Acetaminophen
Acute Kidney Injury
Animals
Biomarkers
Blood Urea Nitrogen
Blotting, Western
Humans
Immunohistochemistry
Kidney
Lipocalins
Male
Neutrophils
Rats*
Acetaminophen
Biomarkers
Lipocalins

Figure

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  Figure 1 Serum blood urea nitrogen (A) and creatinine (B) in male rats treated with AAP and/or DADS. Values are presented as means±SD (n=6). *P<0.05 compared with the control group. †P<0.05 compared with the AAP group.

• 

  Figure 2 Representative photographs of kidney sections treated AAP and/or DADS. Kidney from vehicle control (A) and DADS (D) treated rats showed a normal morphology. However, kidney from an AAP-treated rat (B) showed cast (black arrow), tubular dilation (white arrow), tubular necrosis (black arrow head), and tubular degeneration (white arrow head). Kidney from an AAP&DADS-treated rat (C) showed nearly normal appearance. H&E stain. Bar=50 µm.

• 

  Figure 3 Representative photographs of immunohistochemical analysis of KIM-1 in kidney sections of (A) controls and rats treated with (B) AAP, (C) AAP&DADS, and (D) DADS. Arrows indicate KIM-1 positive cells (brownish-stained cells). Bar=50 µm. (E) The number of KIM-1 positive cells was counted in ten different fields in each section under 100× magnification. Results are presented as means±SD (n=6). **P<0.01 compared with the control group. ††P<0.01 compared with the AAP group.

• 

  Figure 4 Representative photographs of immunohistochemical analysis of NGAL in kidney sections of (A) controls and rats treated with (B) AAP, (C) AAP&DADS, and (D) DADS. Arrows indicate NGAL positive cells (brownish-stained cells). Bar=50 µm. (E) The number of KIM-1 positive cells was counted in ten different fields in each section under 100× magnification. Results are presented as means±SD (n=6). **P<0.01 compared with the control group. ††P<0.01 compared with the AAP group.

• 

  Figure 5 Western blot analysis of KIM-1 and NGAL expressions in rats treated with AAP and/or DADS. Detection of β-actin expression was used as a loading control. The bar graphs show quantitative relative levels of KIM-1 (B) and NGAL (C) protein expressions for vehicle, AAP, AAP&DADS, and DADS-treated rats. Values are presented as means±SD (n=6). **P<0.01 compared with the control group. ††P< 0.01 compared with the AAP group.

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