This study was designed to assess the effect of naringenin (NRG) on simvastatin (SV)-induced hepatic damage in rat and to investigate the effects of these drugs on cytochrome P450 (CYP) 2E1 and 3A1/2 isoforms in order to evaluate the possibility of their coadministration. Hepatic damage in rat was induced by SV (20 and 40 mg/kg/day, po for 30 days). The protective effect of NRG (50 mg/kg/day, po) was identified by estimating liver functions and oxidative stress markers such as lipid peroxidation, reduced glutathione, superoxide dismutase, glutathion s-transferase, and catalase as well as protein profile. DNA fragmentation and histopathological study were carried out to confirm the hepatic damage. An in vitro study was conducted to further evaluate the effect of SV and/or NRG administration on the activities of two microsomal CYP isoenzymes including CYP2E1 and CYP3A1/2. SV exerted an oxidative stress which may contribute to the hepatotoxicity. Administration of NRG in combination with SV significantly improved the liver functions, state of oxidative stress, protein profile, DNA fragmentation, and the histopathological changes. SV and/or NRG have a potential to inhibit CYP3A1/2 and CYP2E1. This study concluded that concurrent administration of NRG with SV provided a protection of liver tissue against the SV-induced hepatic damage. The inhibition of CYP2E1 and CYP3A1/2 by the SV and NRG should be taken into account in order to adjust doses to avoid interaction between SV and NRG and adverse effects of SV.
Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent and immunosuppressant. CLB mutagenicity, teratogenicity, and carcinogenicity are indicated based on their structure and clinical history. This study aims to evaluate the antigenotoxic effect of Cymbopogon citratus essential oil, CC, (75 mg/kg) against CLB (7.5 mg/kg) genotoxicity in rats. GC/MS for essential oil has identified 19 compounds representing approximately 99.7% Geranial was the most abundant (53.5%) followed by Neral (35%) and Myrcene (5.3%). The lowest was α-Muurolene (0. 1%). The marked damage was observed in total genomic DNA and total protein profile of CLB-intoxicated rat's spleen tissues. Lymphocytes single-strand breaks of treated rats were examined by comet assay after CC had ameliorated these effects in a time-dependent manner (5, 10, and 15 days) for spleen and after 48 hours for lymphocytes. In conclusion, this study suggests that Cymbopogon citrates oil possesses antigenotoxic potential in CLBintoxicated rats. It can constitute natural, new, and safe co-therapeutics.
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