Protective Efficacy of Protocatechuic Acid Against Cyclophosphamide‐Induced Nephrotoxicity in Small White Mice

Cyclophosphamide has been well used as an immunosuppressive drug in rheumatoid arthritis and several cancers. This drug or its metabolites cause acute bladder inflammation and may damage the kidneys. The biological activities of protocatechuic acid have been extensively reported. It has shown anti-inflammatory, antioxidant, and neuroprotective effects. This study aims to evaluate the protective effect of protocatechuic acid on cyclophosphamide-induced nephrotoxicity in small white mice. In this experimental study, 40 small white male mice were randomly divided into five groups (8 in each group). The first group received normal saline (1 mL/kg orally) for 10 days, the second group received normal saline (1 mL/kg orally) and cyclophosphamide (200 mg/kg intraperitoneally) for 10 days, the third group, the fourth group, and the fifth received 25, 50, and 100 mg/kg protocatechuic acid, respectively, and 200 mg/kg cyclophosphamide intraperitoneally for 10 days. Twenty-four hours later, blood samples were taken from all animals, and serum levels of BUN, creatinine, KIM-1, and NGAL were measured. The levels of malondialdehyde, nitric oxide, glutathione, superoxide dismutase activity, glutathione peroxidase, catalase, total antioxidant capacity, and tissue necrosis factor were measured in the left kidney tissue. The right kidney was preserved in formalin for tissue sample preparation and subsequent hematoxylin and eosin staining. The results revealed that protocatechuic acid reduced the increase in serum levels of creatinine, BUN, KIM-1, NGAL, malondialdehyde, nitric oxide, and tissue necrosis factor caused by cyclophosphamide in kidney tissue. It also increases glutathione, total antioxidant capacity, and activity of superoxide dismutase, catalase, and glutathione peroxidase enzymes in kidney tissue. Histopathological findings revealed that cyclophosphamide could lead to kidney damage and tubular necrosis. The results revealed that protocatechuic acid reduced biochemical indices and oxidative stress parameters in response to cyclophosphamide-induced nephrotoxicity.