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.

Gallic acid ameliorates busulfan-induced testicular toxicity and damage in mature rats.

Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of adult rats. The adult Wistar rats were assigned as control, BUS: was intraperitoneally (i.p.) treated with busulfan (15 mg/kg, day 7 and 14), GAL + BUS: was co-treated with busulfan (i.p., 15 mg/kg, day 7 and 14) and orally treated (per os) with gallic acid (60 days, 20 mg/kg) and GAL: was treated with gallic acid (per os, 60 days, 20 mg/kg). The results showed that GAL co-treatment increased the numbers of spermatogonia (Type A and B), spermatocytes (primary and secondary) and round spermatids, along with the tubular diameter, epithelial height and gonado-somatic index. In addition, BUS-induced increase in 3ß-hydroxysteroid dehydrogenase and γ-glutamyl transpeptidase activities were inhibited on GAL co-treatment. Similarly, BUS-induced decrease in gluthathione concentration, catalase and superoxide dismutase activities along with increase in myeloperoxidase activity and malondialdehyde concentration were significantly normalized to control values on GAL co-treatment. Busulfan-induced elimination of tubular germ cells was completely prevented by GAL. Overall, GAL may inhibit BUS-mediated spermatogenesis arrest via decreasing inflammatory-mediated oxidative stress in a rat experimental model.

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.

Antioxidant and anti-inflammatory protective effects of rutin and kolaviron against busulfan-induced testicular injuries in rats.

There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3ß-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats.Abbreviations: CAT: Catalase; GSH: Glutathione; 3ß-HSD: 3ß- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species.

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.

Antifertility and profertility effects of the leaves and seeds of fluted pumpkin: Sperm quality, hormonal effects and histomorphological changes in the testes of experimental animal models.

Fluted pumpkin (FP; Telfairia occidentalis) is an edible vegetable, grown in West Africa, that is used in traditional medicine for its regulatory effects on the male gonads. Scientific articles concerning the effects of FP were identified by searching PubMed, PubChem, Scopus, Springer, ResearchGate, Google Scholar and Web of Science; this literature was to better understand the effects of FP seed (FPS) and leaf (FPL) extracts on the testes. Data showed that in experimental animals extracts of FPL and FPS at 1/100 of the lethal dose promoted testis regeneration and improved testosterone concentration and sperm quality, while at higher doses they had antifertility effects. Several extracts of FPS and FPL, including ethanol, aqueous, methanol and hydroethanolic, had protective effects on the testes of study animals at lower doses (≥ 50 mg/kg body weight), but at higher doses (≥ 200 mg/kg body weight) they inhibited hormone synthesis, sperm quality and histomorphological structure, under both normal and disease conditions. The posttreatment effects of FPS on the gonads were reversible in young mature rats and FPS had slight systemic toxic effects. Although, there are inconsistencies in some of the published results, the current evidence suggests that FPS and FPL have both profertility and reversible antifertility effects in experimental animals.

Effect of Anthocleista djalonensis A. Chev Root Extract on Testis of Matured Rats.

OBJECTIVE: To investigate the effects of different extracts of Anthocleista djalonensis on the testis and epididymal sperms of rats. METHODS: Fifty male Wistar rats were randomly divided into 10 groups (n=5 in each group) and orally treated with 50, 100 and 200 mg/kg body weight each of methanol, aqueous ethanol (H-EtOH) and chloroform extracts of A. djalonensis. Corn oil was used as vehicle (2 mL/kg). After 60 days of treatment, testosterone (T) and cholesterol (CHOL) concentrations, catalase (CAT), lactate dehydrogenase (LDH), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and superoxide dismutase (SOD) activities in the testes along with myeloperoxidase (MPO) activities and nitrite concentrations (NO) in the serum and testes as well as sperm quality were measured. RESULTS: T and CHOL concentrations along with 3ß-HSD activity were significantly higher in the animals treated with the low dose than in those treated with the high dose of the chloroform extract (P<0.05). Furthermore, the chloroform extract was more effective than the methanol extract that had the most marginal effect on T level at the high dose and the H-EtOH extract that was only effective at the medium dose. LDH activity was dose-dependently increased by the extracts in all groups. The CAT-SOD antioxidant system was increased in the treated animals at all doses compared to the control values, but the increase in glutathione level reached significant level in those treated with the low dose H-EtOH aqueous ethanol extract (P<0.05). Only the high dose of chloroform extract had significant inhibitory effects on MPO activity (P<0.05). Serum NO concentration was decreased at all doses of the extracts. The inhibitory effects of the extracts on testicular NO concentrations follow this order, chloroform extract > H-EtOH > methanol. Although all extracts at all doses showed excellent stimulatory effects on sperm quality (count, motility and morphology), the methanol extract at the high dose was the most effective on sperm count (P<0.05). CONCLUSION: The chloroform extract of A. djalonensis has better androgen-like and anti-inflammatory effects whereas the methanol extract has the best effect on sperm count.

Dietary fluted pumpkin seeds induce reversible oligospermia and androgen insufficiency in adult rats.

Some components of the human diets are believed to be promising male contraceptive agents. The present study examined the antispermatogenic efficacy, reversibility and toxicity of fluted pumpkin seed-supplemented diet (DFPS) in adult male Wistar rats. Adult rats were given DFPS at 2.5, 5 and 10% for 60 days followed by 60 days post-treatment period. The control animals received normal standard rat diet not supplemented with fluted pumpkin seeds. The sperm quality variables, testosterone and follicle-stimulating hormone (FSH), oxidative status of the testis, steroidogenic enzymes and gamma-glutamyl transferase (γ-GT) activities and the histology of the testis were determined to evaluate the anti-fertility activity of fluted pumpkin seeds. Treatment of animals with DFPS at 5% and 10% resulted in decreased serum and intra-testicular testosterone and FSH concentrations. This effect was associated with decreased activity of 17ß-hydroxysteroid dehydrogenase (17ß-HSD), increased testicular oxidative stress and poor sperm quality in the 10% diet group. After 60 days DFPS post-treatment, intra-testicular 17ß-HSD and γ-GT activities, FSH and testosterone levels recovered to control values. Furthermore, poor sperm motility, count, morphology and viability as well as severe loss of spermatogonia and other matured epithelial germ cells and Sertoli cells observed especially in the 10% DFPS-treated animals reverted to nearly control values 60 days after withdrawal of treatment. Dietary fluted pumpkin seeds may selectively act on the epithelial germ cells, possibly mediated via Sertoli cells, leading to oligospermia, oxidative damage and androgen insufficiency. The reversibility of these effects to near normal levels after withdrawal of treatment justifies further consideration of DFPS as it may be an effective and readily reversible agent that meets the required criteria of a male contraceptive agent.Abbreviations: GC-MS: gas-chromatography mass spectrophotometry; MPO: myeloperoxidase; NO: nitric oxide; DFPS: dietary fluted pumpkin seeds; DFPS (REV): DFPS post-treatment; MDA: malondialdehyde; SOD: superoxide dismutase; CAT: catalase; GSH: glutathione; 3ß-HSD: 3ß-hydroxysteroid dehydrogenase; 17ß-HSD: 17ß-hydroxysteroid dehydrogenase; NAD: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); ITT: intra-testicular testosterone; FSH: follicle-stimulating hormone; FPS: fluted pumpkin seeds; NIST: National Institute Standard and Technology; Av: absolute volume; Ac: cross-sectional area; ST: seminiferous tubules; γ-GT: gamma glutamyl transferase.

Aged coconut oil with a high peroxide value induces oxidative stress and tissue damage in mercury-treated rats.

Background Exposure to mercury (Hg) and the ingestion of peroxidized edible oil represent a health risk. This study evaluated the effects of peroxidized coconut oil (CO) on the liver and kidney of rats treated with Hg. Methods Male albino Wistar rats were administered HgCl2 and CO separately or as a combination for 21 days. The concentrations of glutathione (GSH) and malondialdehyde (MDA), as well as the activities of superoxide dismutase (SOD) and catalase (CAT), which were used as markers of oxidative stress were measured in the liver and kidney homogenates. The activities of gamma glutamyl transferase (γ-GT), lactate dehydrogenase (LDH) as well as the levels of bilirubin and creatinine (CREA) as markers of liver and kidney functions were analyzed in the serum. Results The level of MDA in the kidney and liver homogenates was significantly increased in the HgCl2, CO, and CO+HgCl2 groups when compared to control values (p<0.05). Liver SOD activity and GSH level were increased and CAT activity was decreased, whereas kidney GSH level and SOD activity were decreased and CAT activity was increased in the CO and CO+HgCl2 groups when compared to control values (p<0.05). The increase in CREA and bilirubin levels as well as γ-GT and LDH activities observed in the CO+HgCl2 group when compared to the control values (p<0.05) were associated with pathological changes in both tissues, and were considered to be due to oxidative stress. Conclusions In summary, peroxidized CO and Hg alone or in combination induces oxidative damage in the liver and kidney of rats.

Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol.

CONTEXT: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials. OBJECTIVE: This study was designed to evaluate the protective effects of RUT against cadmium (Cd) + ethanol (EtOH)-induced hepatic and renal toxicity in rats. MATERIALS AND METHODS: Wistar rats were treated with Cd (50 mg/kg) alone or in combination with EtOH (5 mg/kg) and RUT (25, 50 and 100 mg/kg) for 15 days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods. RESULTS: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd + EtOH group and lowest in Cd + EtOH animals co-treated with the highest dose of RUT (2.98 ± 0.34, 10.08 ± 2.32, 4.99 ± 1.21 vs. 1.69 ± 0.33, 6.13 ± 0.28, 3.66 ± 1.12 µmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd + EtOH treated animals compared to Cd + EtOH animals co-treated with 100 mg/kg RUT (2.54 ± 0.08 vs. 1.28 ± 0.04 ppm). Furthermore, RUT at the highest dose protected against Cd + EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86 ± 2.74 vs. 122.52 ± 6.35 µmol/L; 1.77 ± 0.35 vs. 3.23 ± 0.55 mmol/L; 9.56 ± 1.22 vs. 16.21 ± 1.64 U/L; 288.92 ± 40.12 vs. 159.8 ± 18.01 U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd + EtOH animals co-treated with RUT in a dose-dependent manner. DISCUSSION AND CONCLUSION: RUT protected against the combined effects of Cd + EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood.

Effects of co-exposure to atrazine and ethanol on the oxidative damage of kidney and liver in Wistar rats.

Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in rats. In the present study, the toxicity of EtoH (5 g kg-1) on the kidney and liver in the absence or in the presence of different doses of ATZ (50, 100, 300 mg kg-1) was evaluated after 21 days in rats. Results showed that the mixture effects on catalase and superoxide dismutase activities were more severe in both tissues compared to EtoH alone, especially as the dose of ATZ was increased. Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from 20.32% in the EtoH +50 mg kg-1 ATZ-treated rats to 34% in the EtoH +300 mg kg-1 ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain as high as 81% in the EtoH-treated rats and the different combine exposure groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric acid level increased compared to the EtoH values. When the EtoH +300 mg kg-1 ATZ-animals were pretreated with curcumin (an antioxidant), the histopathological changes and peroxidative damages in both tissues were blocked. The exposure of EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.

Antioxidant capacity of some plant foods and beverages consumed in the Eastern Region of Nigeria.

Today plant foods and beverages are receiving more scientific attention because of their potential to curb the effect of free radicals in the human system. The present study reports on the antioxidant potentials of some plants foods and beverages consumed in the Eastern Region of Nigeria. The study made use of the ferric reducing antioxidant power, phenolic and the flavonoid contents assays to assess the quality of the antioxidant potentials of the plant foods and beverages. Of the different classes of foods analyzed the following showed high antioxidant potentials: coffee for beverages, star apple for fruits, thyme for vegetable and spices, and raices for alcoholic beverages. Generally the vegetables and spices registered the highest antioxidant properties. The results obtained in this study could help consumers' choice based on the antioxidant capacity of the samples analyzed.

Antioxidant capacity of some plant foods and beverages consumed in the Eastern Region of Nigeria

Today plant foods and beverages are receiving more scientific attention because of their potential to curb the effect of free radicals in the human system. The present study reports on the antioxidant potentials of some plants foods and beverages consumed in the Eastern Region of Nigeria. The study made use of the ferric reducing antioxidant power; phenolic and the flavonoid contents assays to assess the quality of the antioxidant potentials of the plant foods and beverages. Of the different classes of foods analyzed the following showed high antioxidant potentials: coffee for beverages; star apple for fruits; thyme for vegetable and spices; and raices for alcoholic beverages. Generally the vegetables and spices registered the highest antioxidant properties. The results obtained in this study could help consumers' choice based on the antioxidant capacity of the samples analyzed