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

Shereen Elwakeel,Amina Abdel Rahman

doi: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

Highlights

Cyclophosphamide (CP) is an active alkylating cytostatic and an immunosuppressive mediator that is applied in chemotherapy for Hodgkin’s and non-Hodgkin’s lymphoma, rheumatoid arthritis, leukemia, neuroblastoma, lupus erythematosus, Burkitt’s lymphoma, multiple myeloma, multiple sclerosis, breast, lung cancer, and in organ transplantation (Hamsa & Kuttan, 2012 and Rehman et al, 2012)
The results of the present study reported that a single dose of CP induced kidney damage as evidenced by increased renal function biomarkers, i.e., serum urea and creatinine
Oxidative stress and free radical generation in renal tubular cells have been proposed to be the reason for CP-induced renal damage (Abraham et al, 2007 &AlSaeed et al, 2017)

Summary

Introduction

Cyclophosphamide (CP) is an active alkylating cytostatic and an immunosuppressive mediator that is applied in chemotherapy for Hodgkin’s and non-Hodgkin’s lymphoma, rheumatoid arthritis, leukemia, neuroblastoma, lupus erythematosus, Burkitt’s lymphoma, multiple myeloma, multiple sclerosis, breast, lung cancer, and in organ transplantation (Hamsa & Kuttan, 2012 and Rehman et al, 2012). The active metabolite 4hydroxycyclophosphamide is stable in the presence of the cyclic tautomer aldophosphamide. These two compounds are circulated to tumor cells, where aldophosphamide cleaves to produce active phosphoramide mustard and acrolein. Plants can utilize aromatic substances, such as phenolic acids and flavonoids that exhibit antioxidant properties due to their metal-chelating and hydrogen-donating capacities, allowing to decrease the occurrence of oxidative stress-related diseases (Rao et al, 2010 & Engwa, 2018).In addition, phenolic agents can link with iron and copper metal ions that can cause radical creation through the Fenton reaction and prevent this reaction (Kilic et al, 2019). GA is composed of three hydroxyl groups attached to the aromatic ring in an ortho position (Fig.1) forming the strongest ROS scavenging activity of phenolic acid as well as antioxidant effect (Borde et al, 2011 & Locatelli et al, 2013)

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Results

Conclusion