Oxidative stress indices in rats under immunosuppression

Area of Science:

• Nephrology
• Pharmacology
• Biochemistry

Background:

• Immunosuppressants (IS) can induce oxidative stress (OxS), a factor in chronic allograft nephropathy.
• Antioxidant enzymes like glutathione peroxidase (GPx) are crucial for kidney health.
• Previous studies on IS and OxS in humans are confounded; this study uses a rat model without transplantation.

Purpose of the Study:

• To evaluate the intensity of oxidative stress in rats under chronic immunosuppression.
• To determine the effects of specific immunosuppressive drug combinations on antioxidant enzyme activity and oxidative stress markers.

Main Methods:

• 49 male Wistar rats were administered various combinations of immunosuppressants (tacrolimus, sirolimus, cyclosporine, mycophenolate mofetil, corticosteroids) for 6 months.
• Glutathione peroxidase (GPx) activity and plasma malonyldialdehyde (MDA) concentrations were measured.
• Multiple regression analysis was used to assess drug effects.

Main Results:

• All immunosuppressants, except corticosteroids, significantly decreased GPx activity (P<.001).
• Corticosteroids increased GPx activity (P<.0001).
• Cyclosporine and tacrolimus decreased plasma MDA concentrations (P<.01), while corticosteroids increased them (P<.05).

Conclusions:

• Most immunosuppressive drugs, excluding corticosteroids, impair antioxidant defenses by reducing GPx activity.
• Corticosteroids appear to have a protective effect on GPx activity.
• All tested immunosuppressants, except corticosteroids, demonstrated a damaging effect on proximal tubules.