Protective Effect of Gallic Acid on Cyclophosphamide-Induced Nephrotoxicity, Oxidative Stress, Genotoxicity, and Histopathological Alterations in Male Albino Rats

Elwakeel, Shereen H.B.; Abdel Rahman, Amina

doi:10.21608/eajbsz.2021.207518

Protective Effect of Gallic Acid on Cyclophosphamide-Induced Nephrotoxicity, Oxidative Stress, Genotoxicity, and Histopathological Alterations in Male Albino Rats

Document Type : Original Article

Authors

¹ Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street, Heliopolis, Cairo, Egypt

² Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street, Heliopolis, Cairo,Egypt

10.21608/eajbsz.2021.207518

Abstract

Cyclophosphamide (CP) is a chemotherapeutic agent used to treat various types of cancer. Despite its nervous, hepatic, renal, and cytotoxic side effects, it is a highly effective agent whether used alone or in combination with other chemotherapeutics. This study was designed to examine the prophylactic effects of Gallic acid (GA) on CP-induced acute renal toxicity. Male Wistar albino rats were divided into six groups, 6 animals each: G1 was given normal saline and served as -ve control, while G2 and G3 were given i.p injections of 100 and 200 mg/kg GA, respectively, for 15 days. G4 was used as a +ve control and received a single i.p. injection of CP (150 mg/kg). G5 and G6 were treated with the two different doses of GA for 15 days before receiving a single i.p. injection of CP. Animals were euthanized 24 hrs after the last treatment, and their kidneys were carefully dissected out for histological, immunohistochemical investigation of Zona occluden-1(ZO-1), and biochemical examination, as well as the evaluation of P53, apoptotic markers and tumor necrosis factor-alpha (TNF-α) gene expressions. Blood samples were also taken to determine serum creatinine and urea levels. The intake of GA improved kidney function, as evidenced by lower levels of kidney toxicity markers (urea and creatinine). GA significantly reduced the percent of DNA fragmentation in renal tissue via modulating the levels of glutathione (GSH) and catalase (CAT) enzymes as well as malondialdehyde (MDA). Furthermore, GA reduced renal TNF-α and P53 gene expressions and improved the kidney's histological architecture as well as increasing of ZO-1 immuno-expression. In conclusion, the findings of this study indicate that GA protects against CP-induced renal toxicity via an anti-inflammatory and antioxidant mechanism. We believe that GA may have prophylactic effects against CP-induced nephrotoxicity.

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