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Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats.
Pharm Biol 2015; 53(9):1311-7PB

Abstract

CONTEXT

Cyclosporin A (CsA) is one of the most important immunosuppressive agents. However, its clinical use is strongly limited by several side effects including hepatotoxicity which remains a major clinical problem. Involvement of reactive oxygen species (ROS) in CsA-induced hepatotoxicity has been reported.

OBJECTIVE

This study investigates the potential protective role of wheat germ oil (WGO) as an antioxidant against CsA-induced hepatotoxicity.

MATERIALS AND METHODS

Twenty-four male Wistar albino rats (six animals in each group) received castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.), WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d.

RESULTS

CsA administration significantly increased serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-κB expression were observed in hepatic tissues of CsA-alone-treated rats. Furthermore, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA-alone-treated animals. Moreover, histopathological changes occurred in CsA-alone-treated rats. Concomitant administration of WGO along with CsA improved all these parameters. Most interestingly, the immunosuppressive effect of CsA was not affected by WGO.

CONCLUSION

The present study suggests that concomitant use of WGO might be useful in reducing liver toxicity induced by CsA via inhibition of ROS, iNOS, and NF-κB expression.

Authors+Show Affiliations

Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University , Cairo , Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25858514

Citation

Akool, El-Sayed. "Molecular Mechanisms of the Protective Role of Wheat Germ Oil Against Cyclosporin A-induced Hepatotoxicity in Rats." Pharmaceutical Biology, vol. 53, no. 9, 2015, pp. 1311-7.
Akool el-S. Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats. Pharm Biol. 2015;53(9):1311-7.
Akool, e. l. -. S. (2015). Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats. Pharmaceutical Biology, 53(9), pp. 1311-7. doi:10.3109/13880209.2014.980584.
Akool el-S. Molecular Mechanisms of the Protective Role of Wheat Germ Oil Against Cyclosporin A-induced Hepatotoxicity in Rats. Pharm Biol. 2015;53(9):1311-7. PubMed PMID: 25858514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats. A1 - Akool,El-Sayed, Y1 - 2015/04/10/ PY - 2015/4/11/entrez PY - 2015/4/11/pubmed PY - 2016/4/12/medline KW - Calcineurin inhibitors KW - liver toxicity KW - oxidative damage SP - 1311 EP - 7 JF - Pharmaceutical biology JO - Pharm Biol VL - 53 IS - 9 N2 - CONTEXT: Cyclosporin A (CsA) is one of the most important immunosuppressive agents. However, its clinical use is strongly limited by several side effects including hepatotoxicity which remains a major clinical problem. Involvement of reactive oxygen species (ROS) in CsA-induced hepatotoxicity has been reported. OBJECTIVE: This study investigates the potential protective role of wheat germ oil (WGO) as an antioxidant against CsA-induced hepatotoxicity. MATERIALS AND METHODS: Twenty-four male Wistar albino rats (six animals in each group) received castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.), WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d. RESULTS: CsA administration significantly increased serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-κB expression were observed in hepatic tissues of CsA-alone-treated rats. Furthermore, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA-alone-treated animals. Moreover, histopathological changes occurred in CsA-alone-treated rats. Concomitant administration of WGO along with CsA improved all these parameters. Most interestingly, the immunosuppressive effect of CsA was not affected by WGO. CONCLUSION: The present study suggests that concomitant use of WGO might be useful in reducing liver toxicity induced by CsA via inhibition of ROS, iNOS, and NF-κB expression. SN - 1744-5116 UR - https://www.unboundmedicine.com/medline/citation/25858514/Molecular_mechanisms_of_the_protective_role_of_wheat_germ_oil_against_cyclosporin_A_induced_hepatotoxicity_in_rats_ L2 - http://www.tandfonline.com/doi/full/10.3109/13880209.2014.980584 DB - PRIME DP - Unbound Medicine ER -