Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats

BACKGROUND: Cisplatin (CP) is recommended as a first-line chemotherapeutic agent for solid tumors, however its usage outcomes in severe adverse effects. Acacia hydaspica possesses various phytochemicals and pharmacological activities. The current study aimed to investigate the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP induced aberrations in lipid profile and hepatotoxicity. METHODS: Rats were randomly separated into six groups (n = 6). Group 1 (control) received distilled water orally for 21 days. Groups 2 (CP control) received a single dose of CP (7.5 mg/kg bw, i.p) on day 16, group 3 (Plant control) received AHE (400 mg/kg b.w, oral) for 21 days, group 4 (post treated group); CP received on day 16 and AHE (400 mg/kg b.w/day, p.o.) was administered after CP till day 21, Group 5 (pretreated group) received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16, group 6 (Silymarin + CP) received 100 mg/kg b.w., p.o. (11 doses/21 days) and CP (7.5 mg/kg b.w., i.p.) on day 16. Lipid profile, liver functional tests, oxidative stress markers, antioxidant enzymes status and histopathological changes were examined. RESULTS: The present study revealed that CP caused body weights loss and increase liver index. CP significantly increased serum total lipid, triglycerides and LDL-cholesterol levels. Conversely, it significantly decreased serum HDL-cholesterol level. CP induced marked deteriorations in serum liver function biomarkers, reduced antioxidant enzymes in tissue, while elevated tissue oxidative stress markers along with morphological injuries compared to control rats. Treatment with AHE ameliorated CP induced alterations in lipid profile, serum ALT, AST, ALP and total bilirubin levels and liver weight. Furthermore AHE treatment improved the total protein and antioxidant enzymes levels while decreased the level of MDA, H(2)O(2), and NO. The altered parameters were returned to the control level with AHE pretreatment. Histopathological analysis also supported the biochemical findings. Pretreatment seems to be more effective compared to post treatment indicating protective effect. CONCLUSION: These results reveal that treatment of AHE may be useful in the prevention of CP induced hepatotoxicity due to its antioxidant potential and polyphenolic constituents.