Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression.
This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.
College of Health Sciences, PAAET, Kuwait.
Samy M
SM
Eleawa
Mahmoud A
MA
Alkhateeb
Fahaid H
FH
Alhashem
Ismaeel
I
Bin-Jaliah
Hussein F
HF
Sakr
Hesham M
HM
Elrefaey
Abbas O
AO
Elkarib
Riyad M
RM
Alessa
Mohammad A
MA
Haidara
Abdullah S
AS
Shatoor
Mohammad A
MA
Khalil
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019256:Cadmium Chloride / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004347:Drug Interactions; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D006062:Gonadotropins / Q000096:biosynthesis* / Q000235:genetics; D006651:Histocytochemistry; D007248:Infertility, Male / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000097:blood; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics
D000975:Antioxidants; C494828:Bax protein, rat; D006062:Gonadotropins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013482:Superoxide Dismutase; D019256:Cadmium Chloride; D000077185:Resveratrol