Cyclophosphamide‐induced testicular oxidative‐inflammatory injury is accompanied by altered immunosuppressive indoleamine 2, 3‐dioxygenase in Wister rats: Influence of dietary quercetin

Abstract

This study evaluated the role of quercetin against cyclophosphamide‐induced distortion of rat testicular function. Adult rats were administered cyclophosphamide (100 mg/kg), quercetin (50 mg/kg) and in combination for seven days. Cyclophosphamide caused a significant increase in the activities of indoleamine 2, 3‐dioxygenases (IDO), tryptophan 2, 3‐dioxygenase (TDO), myeloperoxidase (MPO), and elevated the concentrations of interleukin 6 (IL‐6) and interferon‐γ (IFN‐γ). Cyclophosphamide increased testis malondialdehyde (MDA) concentrations but depleted superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px) and glutathione (GSH). However, quercetin co‐administration significantly (p < 0.05) prevented the increased values of IDO, TDO, MPO, IL‐6, IFN‐γ, MDA, SOD, CAT, GSH‐Px and GSH compared with control rats. Also, quercetin co‐treatment significantly increased serum testosterone, follicle‐stimulating hormone (FSH), prolactin, luteinizing hormone (LH), activities of testicular 3β‐hydroxysteroid dehydrogenase (3 β‐HSD), 17β‐hydroxysteroid dehydrogenase (17 β‐HSD) as well as sperm count, motility and viability but reduced abnormal sperm morphology. Quercetin exposure alone did not alter any of the parameters evaluated relative to control. Thus, quercetin protected the testes against cyclophosphamide‐induced alterations in immunosuppressive IDO/TDO activities elicited by oxidative‐inflammatory mediators.

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats

“…Additionally, FSH and LH play a role in regulating Leydig cell function to produce testosterone in males [ 8 ]. CP markedly reduced the serum levels of testosterone, FSH, LH, and prolactin [ 11 ], even at a single dose of 100 mg/kg [ 34 ]. The results of this study indicated that CP affected spermatogenesis by interfering with cellular processes as well as the pituitary–testicular axis.…”

“…HSP significantly enhanced the serum testosterone, FSH, LH, and prolactin levels following bisphenol A administration [ 35 , 36 ]. Also, the administration of other flavonoids, including quercetin [ 11 ] or morin [ 37 , 38 ], or rutin [ 38 ], improved serum levels of testosterone, FSH, LH, and prolactin. This could be attributed to the protective roles of flavonoids in terms of anti-inflammatory and antioxidant ability.…”

“…This could be attributed to the flavonoid’s ability to prevent tissue damage, prevent the inactivation of steroidogenesis, and increase gonadotropin release [ 81 , 82 ]. CP treatment significantly decreases steroidogenic genes that include StAR, CYP11A1, CYP17A1, HSD17B, and CYP1719A1 compared with other groups [ 11 , 83 ]. Cisplatin has been reported to induce similar impacts [ 84 , 85 ].…”

“…CP has been reported to impact male fertility both centrally and peripherally via downregulating the hypothalamic–pituitary–gonadal (HPG) axis through affecting the hypothalamic Kiss1 mRNA expression and gonadotropin secretion, testicular steroidogenesis, testosterone synthesis, and eventually spermatogenesis [ 9 , 10 ]. Furthermore, Cp has been linked to direct testicular oxidative stress and DNA damage leading to testicular degeneration [ 11 , 12 ].…”

The antioxidant/anti‐inflammatory protective effects of rutin against ethanol‐induced testicular perturbation in rats: Involvement of the immunosuppressive indoleamine 2,3‐dioxygenase

“…A major physiological pathway of tryptophan (Trp) catabolism involves the kynurenine pathway via the action of the hepatic tryptophan‐2,3‐dioxygenase (TDO) and the ubiquitous IDO 43 . Pro‐inflammatory cytokines, IL‐6 interleukins and their accompanying oxidative biomarkers are well known to trigger the activity/expression of IDO, which usually favours the accumulation of kynurenine and LPO that is associated with testicular injury 9 . Our findings demonstrated that EtOH exposure aggravated IDO expression/activity in the testes.…”