BACKGROUND: Nephrotoxicity is one of the adverse effects of cyclophosphamide which is a cytotoxic alkylating agent that may be nephrotoxic both in humans and animal models by generating reactive oxygen species. Therefore, purpose of this study was to investigate whether antioxidants like zinc and ascorbic acid as well as most prominent traditional-based plant material like Cedrus deodara root oil could decrease the intensity of toxicity caused by cyclophosphamide in albino rats. OBJECTIVES: · To evaluate the histomorphological changes in cyclophosphamide-induced kidney damage in albino rats. · To determine the role of zinc and ascorbic acid in cyclophosphamide-induced renal damage in rat model. · To assess the phytoprotective role of cedrus deodara root oil in cyclophosphamide-induced kidney damage. · To observe the renal function tests in the controls and experimental groups of animals. · To observe the changes in the antioxidative enzymes in the controls and experimental groups of animals. MATERIALS AND METHODS: The present study was conducted at Isra University, Hyderabad and Al-Tibri Medical College, Karachi. The animals used for this study were adult albino rats of (Wistar strain) 200-250 g of either gender and were procured from the animal house of Al-Tibri Medical College, Karachi. They were maintained on well balanced laboratory diet. The animals were kept in 12/12 hour light-dark cycle and water was provided freely x throughout the experimental period. The temperature where the animals were placed was maintained between 25 – 30˚C. total sixty (60) albino rats was taken in this experimental study. Animals were divided into six groups and each group comprised of ten (10) rats placed in separate cages. Control group A were given normal saline 1 ml/ day intraperitoneally for 21 days. Experimental group B received single dose of cyclophosphamide 1mg/100g intraperitoneally on first day of study. Experimental group C received 1mg/100g cyclophosphamide and 500 mg/100g ascorbic acid orally daily for 21 days. Experimental group D received cyclophosphamide 1mg/100g single dose on first day along with zinc-sulphate 0.1mg/100g daily for 21 days. Animals of experimental group E received cyclophosphamide 1mg/100g on first day intraperitoneally along with ascorbic acid 25 mg/100g, zinc sulphate 0.05 mg/100g and Cedrus deodara root oil 0.05 mg/100g intraperitoneally for 21 days. At the end of 21 day of treatment protocol, rats were anesthetized by ether inhalation and scarified for biochemical and histopathological examination. Blood sample 5.0 ml was taken through cardiac puncture and transferred into sterilized gel tubes for estimation of biochemical parameters. Kidneys were removed out after laparotomy and preserved at -80˚C for tissue slicing. Thick tissue sections 5μ were prepared by rotary microtome. The tissue sections were mounted on well cleaned and gelatinized slides and were stained with Hematoxylin and Eosin according to Bancroft and Stevens method for histopathological findings. The data obtained was then analyzed on SPSS version 21.0 (IBM, corporation, USA) P-value 0.05 was taken as significant. xi RESULTS: The results of present study showed that serum superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione (GSSH), catalase, Malondialdehyde (MDA), creatinine, urea, uric acid (UA) and electrolytes like Na+, K+, Cl-, Ca++ and Mg++ were found statistically significant among the control and experimental groups of animals. Animals of group B when compared with control group A and other groups showed statistically significant difference of antioxidant enzymes (p<0.0001). experimental group F when treated with (cyclophosphamide, ascorbic acid and zinc sulphate) showed significant increase in antioxidant enzymes as well as significant improvement were seen in urea, creatinine and serum electrolytes (p=0.001). CONCLUSION: The present study revealed that the Cedrus deodara root oil exerted potent free radical scavenging property and showed potent antioxidant activity. Hence, it may be concluded that the mechanisms of nephroprotection by herbal agent Cedrus deodara root oil in cyclophosphamide treated animals could be due to its antioxidant and free radical scavenging activity.