title: Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: comparison with celecoxib.
abstract: Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50mg/kg) and celecoxib (5mg/kg) were orally administered to Wistar rats once daily for 21days starting 1h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50mg/kg dose of chrysin exerted comparable protective actions to celecoxib.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Hebatallah A
authors.initials: HA
authors.lastname: Darwish
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address: hany.arab@pharma.cu.edu.eg.
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Rania M
authors.initials: RM
authors.lastname: Abdelsalam
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D005419:Flavonoids; D018836:Inflammation Mediators; D010750:Phosphoproteins; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000098682:Steroidogenic Acute Regulatory Protein; C043561:chrysin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D000068579:Celecoxib
keywords: Apoptosis; Celecoxib; Chrysin; Inflammation; Rheumatoid arthritis; Testicular dysfunction