Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis.
The present study was conducted to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cyclophosphamide (CP)-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. Forty-eight healthy adult male Sprague-Dawley rats were divided into six groups of eight rats each. The control group was treated with placebo; the LC, EA and CP groups were given LC (10 mg kg(-1)), EA (2 mg kg(-1)) and CP (15 mg kg(-1)), respectively, alone; the CP+LC group was treated with a combination of CP (15 mg kg(-1)) and LC (10 mg kg(-1)); and the CP+EA group was treated with a combination of CP (15 mg kg(-1)) and EA (2 mg kg(-1)). All treatments were maintained for 8 weeks. At the end of the treatment period, bodyweight and the weight of the reproductive organs, sperm concentration and motility, testicular tissue lipid peroxidation, anti-oxidant enzyme activity and apoptosis (i.e. Bax and Bcl-2 proteins) were determined. Administration of CP resulted in significant decreases in epididymal sperm concentration and motility and significant increases in malondialdehyde levels. Although CP significantly increased the number of Bax-positive (apoptotic) cells, it had no effect on the number of Bcl-2-positive (anti-apoptotic) cells compared with the control group. However, combined treatment of rats with LC or EA in addition to CP prevented the development of CP-induced lipid peroxidation and sperm and testicular damage. In conclusion, CP-induced lipid peroxidation leads to structural and functional damage, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protect against the development of these detrimental effects.
Türk
Gaffari
G
Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Firat University, 23119, Elaziğ, Turkey. gturk@firat.edu.tr
Ceribaşi
Ali Osman
AO
Sakin
Fatih
F
Sönmez
Mustafa
M
Ateşşahin
Ahmet
A
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D004610:Ellagic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D000077276:Lycopene; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013739:Testosterone / Q000097:blood
D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D004610:Ellagic Acid; D002338:Carotenoids; D013739:Testosterone; D008315:Malondialdehyde; D003520:Cyclophosphamide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077276:Lycopene