Hesperetin protects testicular toxicity of doxorubicin in rat: Role of NFκB, p38 and caspase-3

• Published in: Food and chemical toxicology Vol. 49; no. 4; pp. 838 - 847
• Main Authors: Trivedi, P.P., Tripathi, D.N., Jena, G.B.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2011; Elsevier
• Subjects: Animals; Apoptosis; Biological and medical sciences; Caspase 3 - metabolism; caspase-3; DNA damage; dose response; Doxorubicin; Doxorubicin - antagonists & inhibitors; Doxorubicin - toxicity; drug therapy; Drug toxicity and drugs side effects treatment; General pharmacology; Genotoxicity; Hesperetin; Hesperidin - pharmacology; Immunohistochemistry; Lipid Peroxidation - drug effects; Male; Medical sciences; NF-kappa B - metabolism; Oxidative stress; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; spermatozoa; testes; Testis; Testis - drug effects; tissues; toxicity; Toxicity: urogenital system; toxicology; transcription factor NF-kappa B; Testis; Oxidative stress; DMSO; Genotoxicity; OTM; MDA; Doxorubicin; SD; LMPA; TUNEL; NMPA; CMC; GSH; EtBr; Hesperetin; H&E; ip; DOX; EDTA; DNA; TL; TM; HBSS; po; Apoptosis; Antineoplastic agent; Rat; Toxicity; Cysteine endopeptidases; Rutaceae; Testicle; Medicinal plant; Prevention; Isomerases; Dicotyledones; Angiospermae; Transcription factor NFκB; DNA topoisomerase (ATP-hydrolysing); Fruit; Enzyme; Transferases; Rodentia; Enzyme inhibitor; Mitogen-activated protein kinase; Topoisomerase II inhibitor; Citrus; Peptidases; Vertebrata; Antibiotic; Mammalia; Cell death; Plant origin; Hydrolases; Anthracyclins; Spermatophyta
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2010.12.005

Doxorubicin is a widely used chemotherapeutic agent causing serious dose-dependent toxicity to non-target tissues such as testis. Its testicular toxicity is mainly due to the induction of oxidative stress. Hesperetin exerts its beneficial effects against oxidative stress-induced cellular damage. In the present investigation, doxorubicin was administered intraperitoneally at the dose of 4 mg/kg bw/week for a period of 5 consecutive weeks. Hesperetin was administered at the doses of 25, 50 and 100 mg/kg bw per oral by gavage for 5 consecutive days in a week for 5 weeks. Animals were sacrificed 1 week after the last injection of doxorubicin. The results of the present study clearly indicate the prevention of oxidative stress, DNA damage and the cellular toxicity by hesperetin treatment as evident from the analysis of biochemical parameters, comet assay, halo assay, Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assay, immunohistochemistry and histology. Hesperetin protection against doxorubicin-induced germ cell toxicity was further evident from the sperm count and sperm head morphological evaluation. Moreover, the role of nuclear factor-kappa B, p38 and caspase-3 on hesperetin-mediated protection against doxorubicin-induced testicular toxicity was also investigated. The present study clearly revealed the amelioration of doxorubicin-induced testicular toxicity by the intervention with hesperetin.