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

This study investigated the influence of rutin against EtOH-induced testicular impairment in rats and the involvement of the indole-aminergic pathway. Four groups of eight rats each were orally exposed to drinking water (Group 1), EtOH (5 g/kg bwt, Group 2), R (5 g/kg bwt, Group 3), and EtOH + R (5 g/kg bwt + 50 mg/kg bwt, Group 4) via gavage for 15 days. Results showed that exposure to EtOH significantly (p < 0.0001) reduced the testicular antioxidant system and increased lipid peroxidation (LPO) relative to control. We observed a significant (p < 0.0001) increase in the inflammatory biomarkers, with attendant disruption in the testicular histological structure and concomitant elevation in the activities of indoleamine 2,3-dioxygenase (IDO), in comparison with control and no noticeable effects in tryptophan 2,3-dioxygenase (TDO) activity across the groups. Rutin-only exposed group did not show any alteration in the measured parameters when compared with the control. Rutin co-exposure augmented the antioxidant system, prevented histological damage, reduced LPO and inflammation, and thus, lowered EtOH-mediated increase in IDO activity, compared with control. Overall, these findings reveal the involvement of the indole-aminergic pathway in rutin's protective influence against EtOH-induced testicular impairment in rats.

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

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 3ß-hydroxysteroid dehydrogenase (3 ß-HSD), 17ß-hydroxysteroid dehydrogenase (17 ß-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.

Cyclophosphamide instigated hepatic-renal oxidative/inflammatory stress aggravates immunosuppressive indoleamine 2,3-dioxygenase in male rats: Abatement by quercetin.

The hepatic-renal toxicity associated with cyclophosphamide (CYP) treatment in both animals and humans have been reported. Quercetin, a dietary flavonoid, is known to elicit beneficial health effects. However, the influence of quercetin on the hepatic-renal toxicity associated with CYP-instigated indoleamine 2,3-dioxygenase is unavailable in the literature. The current study evaluated the effects of quercetin on the dysfunctional hepatic-renal status triggered by CYP exposure in rats. Experimental animals were exposed to CYP (100 mg/kg) or co-treated with quercetin (50 mg/kg) every other day for 7 days. Results revealed that quercetin treatment significantly assuaged CYP-mediated oxidative-inflammatory response, as well as augmenting serum levels of thyroid hormones. Additionally, quercetin attenuated CYP-induced reduction in antioxidant enzyme activities and enhanced hepatic-renal function markers, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and levels of urea and creatinine. Quercetin efficiently mitigated CYP-mediated increase in myeloperoxidase (MPO) activity, levels of nitric oxide and interleukin-6 (IL-6) in liver and kidney of rats. CYP-induced increase in the activities of immunosuppressive indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO) in the tissues was abated in quercetin co-treated rats. In conclusion, Quercetin ameliorated deficits in the hepatic-renal function in CYP-exposed rats by lowering the activities/expression of immunosuppressive IDO and TDO via diminution of oxidative-inflammatory stress.

Selenium nanoparticles and metformin ameliorate streptozotocin-instigated brain oxidative-inflammatory stress and neurobehavioral alterations in rats.

Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p < 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic ß-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p < 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.

Loranthus micranthus nanoparticles abates streptozotocin-instigated testicular dysfunction in Wistar rats: Involvement of glucose metabolism enzymes, oxido-inflammatory stress, steroidogenic enzymes/protein and Nrf2 pathway.

Loranthus micranthus (African mistletoe)-Loranthaceae family, is used in Nigerian traditional medicine for treating male infertility and lowering diabetic blood sugar levels. We investigated possible mechanism(s) involved in mitigation of L. micranthus leaves nanoparticles (LMLNPs) on streptozotocin (STZ)-induced testicular alterations. Type two diabetes mellitus (T2DM) was induced in male rats following 2 weeks feeding with fructose and single intraperitoneal injection of STZ. Control (nondiabetic) and (diabetic) rats received buffer only. Diabetic rats were treated with metformin or LMLNPs (two different doses) for 28 days. Hormonal profile, oxido-inflammatory stress parameters, glucose metabolism and steroidogenic enzymes/regulatory protein (StAR) and Nuclear factor erythroid 2-related factor 2 (Nrf2) protein in testes and sperm parameters were evaluated. Metformin and LMLNPs treatment significantly reduced blood glucose level in diabetic rats. Furthermore, LMLNPs enhanced glucose metabolism and testicular steroidogenic enzymes/protein, increased reproductive hormone levels and sperm functional parameters in diabetic rats. Additionally, LMLNPs suppressed testicular oxido-inflammatory stress biomarkers and inhibited lipid peroxidation in diabetic rats while augmenting Nrf2 pathway. Conclusively, LMLNPs potently reversed adverse effects of T2DM testicular dysfunction of rats. Use of LMLNPs in abating diabetic consequences proves an acceptable alternative to traditional crude extract preparations, as a result of better packaging and preservation.

Alteration in sperm characteristics, endocrine balance and redox status in rats rendered diabetic by streptozotocin treatment: attenuating role of Loranthus micranthus.

OBJECTIVES: Loranthus micranthus is widely used in Nigerian folklore treatment of male infertility and diabetes complications. We investigated this claim in rats rendered diabetic by streptozotocin (STZ). METHODS: Induction of diabetes mellitus in adult male Wistar rats was by intraperitoneal injection of STZ (60  mg/kg). The diabetic rats were thereafter treated orally once/day with 5 mg/kg Gilbenclamide or L. micranthus (100 mg/kg or 200 mg/kg) and monitored for 14 days. Clinical observations, hormonal profile, oxidative stress parameters, glucose metabolism enzymes, histopathological examination, apoptotic marker immunoreactivity and western blotting in testes and sperm parameters were evaluated to examine effects of L. micranthus on STZ-diabetic rats. RESULTS: L. micranthus treatment significantly reduced the blood glucose level (45.9% and 84.7% on the 7th and 14th post-treatment days, respectively); increased antioxidant status, improved microarchitecture of testes, reduced lipid peroxidation and increased BCl-2 protein expression in diabetic rats relative to control. Furthermore, treatment with L. micranthus increased steroidogenic enzymes activities, levels of steroid hormones and improved sperm quality, relative to control. CONCLUSION: The anti-diabetic and aphrodisiac properties exhibited by L. micranthus could be contingent on its ability to restore a balance to the compromised redox status that characterizes male reproductive dysfunction in diabetes.