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HEPATOTOXIC EFFECT OF 17-OXIMINO-5-ANDROSTEN-3β-YL BENZOATE ON RATS

Abstract

Neelima Dhingra1, Anna Ara Khan1, Gousia Jan1 and Vijayta D Chadha2*

Introduction and positioning of the hydroximino group on the parental steroid skeleton has significant effect on the activity profile of steroidal compounds. Earlier reports described the synthesis and evaluation of 17-Oximino-5-androsten-3β-yl ester derivatives as potential cytotoxic agents on liver cancer cell lines (Hep-2) using Sulphorodamine B6 assay. The 17-Oximino-5-androsten-3-yl benzoate displayed significant cytotoxicity against liver as compared to standard reference drugs. The current study was undertaken to investigate further the in vivo effect of the synthesized derivative on the liver of rats following one month treatment. Male SD rats were divided into two groups viz: normal control and 17Oximino-5-androsten-3β-yl ester derivative treated (dose 10mg/Kg body weight, intraperitoneally). After one month of treatment, the hepatotoxicity was assessed by estimating the levels of hepatic marker enzymes, oxidative injury and histopathological studies in the liver of control and treated rats. The study revealed a significant increase in the levels of glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT) and alkaline phosphatase (ALP) in the serum and liver of 17-Oximino-5androsten-3-yl benzoate treated rats when compared to control animals. Further, increased lipid peroxidation (LPO) was accompanied by a decrease in glutathione (GSH) level. However, the activities of glutathione-s-transferase, (GST), superoxide dismutase (SOD) and catalase were found to increased significantly in the treated group. Histopathological observations also indicated marked alterations in the histoarchitecture of liver in response to 17-Oximino-5-androsten-3β-yl ester derivative treatment. In conclusion, the synthesized compounds possess hepatotoxicity and exerts its cytotoxic action by oxidative cell injury. 

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