Effects of Dulaglutide in Doxorubicin Induced Renal Toxicity in Rats.

Abstract

Objective: The present study was designed to determine the anti-inflammatory and antioxidant effects of dulaglutide (DUL) on doxorubicin (DOX) -induced acute kidney injury (AKI).

Methods: Twenty-eight male rats were randomly allocated into four groups: the negative control group (received Distilled water), the positive control group (received Distilled water and a single dose of DOX), DUL 0.2 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX), and DUL 0.6 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX). All DOX doses (20 mg/kg) were given at day 13th of the study and all treatments were administered intraperitoneally for 14 days. On day fifteenth, the rats were sacrificed, and blood was collected to measure the complete blood count (CBC), Neutrophile/Lymphocyte Ratio (NLR), Monocyte/Lymphocyte Ratio (MLR), And Platelet/Lymphocyte Ratio (PLR), C-reactive protein (CRP), blood urea nitrogen (BUN), and serum creatinine (SCr). The right kidney was used for histopathological examination, while the left kidney was homogenized to assess the renal tissue levels of malondialdehyde (MDA), total antioxidant capacity (TAOC), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL).

Results: DOX induces acute kidney injury was demonstrated by significant elevations in BUN, SCr, and CRP levels. DUL significantly lowered the levels of BUN, SCr, and CRP, and reduced the levels of blood inflammation markers, including NLR and MLR. Additionally, it resulted in a significant reduction in the renal tissue levels of MDA, IL-1β, and TNF-α, while the level of TAOC was significantly elevated. These findings were supported by histopathological assessments.

Conclusion: The present study indicates that DUL mitigates doxorubicin-induced kidney damage by reducing oxidative stress and inflammation.