Abstract
Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.
Highlights
DMoial.bSecit.e2s017m, 1e8l,li9t1u9s (DM) is a metabolic disorder accompanied by hyperglycemia du2eoft1o5 inadequate insulin secretion or insulin resistance [1]
Our data revealed that the rats’ body weight and relative weight of accessory glands decreased during the course of diabetes; these results were consistent with those obtained by Ozdemir et al [14], who attributed the reduction of body weight to the breakdown of tissue protein in the diabetic group
Diabetic rats showed hyperglycemia and decreased serum insulin level in the current study; this finding is in harmony with results from Ballester et al who found that diabetic rats displayed a reduction in the concentration of serum insulin, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) [18]
Summary
Diabetes mellitus (DM) is a metabolic disorder accompanied by hyperglycemia due to inadequate insulin secretion or insulin resistance [1]. Spermatogenesis is associated with many diseases, Int. J. DMoial.bSecit.e2s017m, 1e8l,li9t1u9s (DM) is a metabolic disorder accompanied by hyperglycemia du2eoft1o5 inadequate insulin secretion or insulin resistance [1]. Spermatogenesis is associated with many dfoisreeaxsaems, pfoler, eDxMam, cpolero, nDaMry, choeraornt adriysehaesaesrt, adnisdeachserso,nainc dlivcehrrodnisicealsiveesr[2d]i.sDeaMsesha[2s]a. NTthoisf phoiglyhunasmaotuurnatteodf fpatotlyyuacnisdatiunrathteedabfasettnyceacoifdanintiothxiedaanbtsemnecechoafniasmntiorexniddaenrst meacmhmanailsimanresnpderemrsamtoazmoammaloiarne svpuelrnmeraatbolzeoatomooxriedavtuivlneerdaabmleatgoeo[x4i]d, awtihverdeaDmMageis[4re],lawtehderteoDthMe iosvreerlpartoedutcotitohne oofvceerlpluroladrurcetaiocntivoef ocxeyllguelanrsrpeeacciteisve(RoOxSy)gethnastpinesctieigsa(tReOteSs)titchualat rininstjuigraietes [t5e]s.tiTcuhluasr, int jhuurriets f[e5r]t.iTlihtyu, sw, ihtihchurmtsigfehrttiblietyim, wphliiccahtemdiignhltobweeirmfeprltiiclaittyedininmlaolweser[6f]e.rtility in males [6]. Thymoqquuiinnoonnee (T(TQQ; 2; -i2s-oisporpoproypl-y5l--m5-emtheythl-y1l,-41-b,4e-nbzeonqzuoqinuoineo)nies)thise atchteiveaicntigvreedinengtreodfiNenigt elolaf sNatigiveallaseseadtsivwa istheevdasriwouitshphvaarrmioaucsolpohgaicraml apcootleongtiacalsl ipncoltuednitniaglsaninticolxuiddianngt, antiocaxnidcaenr,t,anatnidticaabnectiecr,, anti-diniafblaemticm, aatnotriy-i,naflnadmamnatitmoriyc,roabnidalaancttiimvitcireosb[i7a,l8a].ctSievviteireasl[s7t,u8]d.ieSsevsehroawl estdudthieast sThQowsiegdnitfhicaatnTtlQy ismigpnrifiovcaendtlsyeimmepnroqvuedalsiteymaendquraelpitryodanudctriveperochdaurcaticvtercishtaicrascotefrimsticse oefxmpoicseeedxptooshedeatto shteraetsstr[e9s],s [r9e]-, eres-teasbtlaisbhliesdhesdpesprmeramtoagtoegneensiessiasftaefrtetrestetisctuiclualrairnijnujruyryininrartasts[1[01]0,],aannddccoonntrtroolleleddmmeetthhoottrreexxaattee--iinndduuced testicular damage in mice [11] aand rraatts [[1122]]..AAddddiittiioonnaallllyy, TQ protects rats from the tteessticular damage induced bbyycacdamdmiuimumexpeoxspuorseutrherotuhgrhouitgshanittisoxaidnatinotxaidndanatntai-nindflamntmi-iantfolraymamctaivtoitriyes a[1c3ti]v. Thymoqquuiinnoonnee (T(TQQ; 2; -i2s-oisporpoproypl-y5l--m5-emtheythl-y1l,-41-b,4e-nbzeonqzuoqinuoineo)nies)thise atchteiveaicntigvreedinengtreodfiNenigt elolaf sNatigiveallaseseadtsivwa istheevdasriwouitshphvaarrmioaucsolpohgaicraml apcootleongtiacalsl ipncoltuednitniaglsaninticolxuiddianngt, antiocaxnidcaenr,t,anatnidticaabnectiecr,, anti-diniafblaemticm, aatnotriy-i,naflnadmamnatitmoriyc,roabnidalaancttiimvitcireosb[i7a,l8a].ctSievviteireasl[s7t,u8]d.ieSsevsehroawl estdudthieast sThQowsiegdnitfhicaatnTtlQy ismigpnrifiovcaendtlsyeimmepnroqvuedalsiteymaendquraelpitryodanudctriveperochdaurcaticvtercishtaicrascotefrimsticse oefxmpoicseeedxptooshedeatto shteraetsstr[e9s],s [r9e]-, eres-teasbtlaisbhliesdhesdpesprmeramtoagtoegneensiessiasftaefrtetrestetisctuiclualrairnijnujruyryininrartasts[1[01]0,],aannddccoonntrtroolleleddmmeetthhoottrreexxaattee--iinndduuced testicular damage in mice [11] aand rraatts [[1122]]..AAddddiittiioonnaallllyy, TQ protects rats from the tteessticular damage induced bbyycacdamdmiuimumexpeoxspuorseutrherotuhgrhouitgshanittisoxaidnatinotxaidndanatntai-nindflamntmi-iantfolraymamctaivtoitriyes a[1c3ti]v. iTtiheesre[f1o3r]e., Tthheerperfeosren, thsetupdreysewnat stcuodnydwuactsecdontoduecvtaelduatoteevthaeluamteetlhioeraamtievleioerfafteicvteoeffTecQt oofnTQdioabnedticabmetaiclemraltes rcaotnscceorncinegrntihnegitnhteraicnetlrlauclealrluplaatrhpwaathywbyaywbhyicwhhiticmhaitymbeayusbeefuulsteofudletcoredaesceredaisaebedtiiacbientfiecritnilfietyr.tility
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