Quercetin and rutin ameliorates sulphasalazine-induced spermiotoxicity, alterations in reproductive hormones and steroidogenic enzyme imbalance in rats.

Certain dietary flavonoids exhibit protective potentials against drug-induced male reproductive toxicities. We investigated the protective effects of quercetin and rutin on sulphasalazine-induced alterations in steroidogenic enzyme activity, hormone profile and spermiotoxicity in rats. Sulphasalazine (SASP, 600 mg/kg bw) was administered alone or in combination with quercetin (20 mg/kg bw) or rutin (10 mg/kg bw) for 14 days. SASP treatment significantly increased relative weights of the epididymis and seminal vesicles. Also, testicular and epididymal sperm numbers (TSN, ESN), motility, daily sperm production (DSP) and acrosome reaction (AR) significantly decreased. SASP altered plasma testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels while testicular cholesterol levels, 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) activities were decreased. Elevated malondialdehyde levels and concomitant decrease in reduced glutathione, glutathione-S-transferase, peroxidase and superoxide dismutase activities were evident in testis and epididymis of SASP-treated rats. Quercetin or rutin co-treatment with SASP significantly reversed organ weights, preserved sperm integrity, restored plasma hormone levels and increased cholesterol levels, 3ß-HSD and 17ß-HSD activities in testis. Both flavonoids also prevented oxidative stress in testis and epididymis of SASP-treated rats. Quercetin and rutin protect against the negative effects of SASP treatment on reproductive capacity in male rats.

Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic ulcerative colitis in mice.

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G and SZ significantly prevented disease activity index and aberrant crypt foci formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression of tumor necrosis factor alpha, interleukin-1ß, inducible nitric oxide synthase, Regulated on activation, normal T cell expressed and secreted (RANTES), and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G effectively protected against colonic oxidative damage by augmenting the antioxidant status with marked decrease in lipid peroxidation levels in DSS-treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65), p38, cyclooxygenase-2, and ß-catenin whereas it enhanced IL-10 and adenomatous polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS-induced chronic UC via anti-inflammatory and antioxidative mechanisms and preservation of the Wnt/ß-catenin signaling pathway.

6-Gingerol improves testicular function in mice model of chronic ulcerative colitis.

The persistent inflammation and oxidative stress at the local site in ulcerative colitis reportedly extend to the testes via systemic circulation resulting in testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in mice was investigated in this study. Chronic ulcerative colitis was induced in mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles. Each cycle consisted of 7 consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination with DSS-treated water during the three cycles. SZ served as standard reference drug for colitis in this study. 6G significantly prevented the incidence of rectal bleeding, decrease in the body weight gain and colon mass index in DSS-exposed mice. 6G significantly prevented colitis-mediated decreases in luteinizing hormone, follicle-stimulating hormone and testosterone and decreases oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with concomitant augmentation of antioxidant enzymes activities, sperm characteristics, marker enzymes of testicular function and histoarchitecture in DSS-exposed mice. 6G exerted protective influence against ulcerative colitis-induced testicular damage via mechanisms involving its antioxidant and anti-inflammatory properties.

Sub-Acute Toxicity Study of Ethylene Glycol Monomethyl Ether on the Antioxidant Defense System of the Testes and Epididymes of Wistar Rats.

Ethylene glycol monomethyl ether is a toxicant with wide industrial applications. This study is aimed atinvestigating its effect on the antioxidant system of the reproductive organs of male rats. Fifty male Wistar rats weredistributed into five groups. Group I received distilled water, Groups II-V received EGME at 100, 200, 300 and 400 mg/kgbody weight respectively. All administrations were done orally for fourteen days and the weight was monitored weekly. Onday fifteen, the animals were sacrificed and reproductive organs were collected and weighed. The testes and epididymeswere processed for the biochemical estimations, histopathology and spermatozoa analysis. The percentage body weightgained weekly and the relative weight of the testes reduced significantly (p < 0.05) in the treatment groups. The spermatozoaanalysis showed decreases in the treatment groups. In the testis and epididymis, various antioxidant parameters such assuperoxide dismutase and glutathione-S-transferase were affected. The histopathology results confirmed the biochemicalfindings. The study suggests that EGME exerts deleterious effects on the testes and epididymes by increasing the oxidativeload in rats.

6-Gingerol-rich fraction prevents disruption of histomorphometry and marker enzymes of testicular function in carbendazim-treated rats.

Previous investigations demonstrated that 6-gingerol-rich fraction (6-GRF) prevented testicular toxicity via inhibition of oxidative stress and endocrine disruption in CBZ-treated rats. The influence of 6-GRF on alterations in histomorphometry and marker enzymes of testicular function in CBZ-treated rats which hitherto has not been reported was investigated in this study. The animals were orally administered either CBZ (50 mg/kg) alone or in combination with 6-GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Histomorphormetric analysis demonstrated that 6-GRF significantly prevented CBZ-mediated increase in the organo-somatic index of the testes and seminiferous tubular diameter as well as the reduction in epithelium height and tubular length of testes in the rats. Similarly, 6-GRF ameliorated CBZ-induced disruption in the epithelium height as well as in the proportion of tubule and interstitium of the epididymis the treated rats. Furthermore, 6-GRF prevented CBZ-mediated increase in testicular acid phosphatase activity and the decrease in testicular alkaline phosphatase, aminotransferases, glucose-6-phosphate dehydrogenase and lactate dehydrogenase activities. Moreover, 6-GRF ameliorated CBZ-induced reduction in the testicular and epididymal sperm count and sperm motility in the treated rats. Conclusively, 6-GRF enhances key functional enzymes involve in spermatogenesis and maintains histo-architecture of testes and epididymis in CBZ-treated rats.

6-Gingerol-rich fraction from Zingiber officinale ameliorates carbendazim-induced endocrine disruption and toxicity in testes and epididymis of rats.

This study evaluated the protective effects of 6-gingerol-rich fraction (6-GRF) from Zingiber officinale on carbendazim (CBZ)-induced reproductive toxicity in rats. Adult male rats were treated with either CBZ (50 mg/kg) alone or in combination with 6-GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Gas chromatography-mass spectrometry (GCMS) analysis revealed that 6-GRF consists of ten bioactive chemical components with 6-gingerol being the most abundant (30.76%). Administration of 6-GRF significantly (p < .05) prevented CBZ-mediated increase in absolute and relative testes weights as well as restored the sperm quantity and quality in the treated rats to near control. In testes and epididymis, 6-GRF significantly abolished CBZ-mediated increase in oxidative damage as well as augmented antioxidant enzymes activities and glutathione level in the treated rats. Moreover, CBZ administration alone significantly decreased plasma levels of testosterone, thyrotropin, triiodothyronine and tetraiodothyronine, whereas follicle-stimulating hormone was significantly elevated without affecting luteinising hormone and prolactin levels when compared with the control. Conversely, 6-GRF ameliorated the disruption in the hormonal levels and restored their levels to near normalcy in CBZ-treated rats. Collectively, 6-GRF inhibited the adverse effects of CBZ on the antioxidant defence systems, hormonal balance and histology of the testes and epididymis in rats.

Insecticide chlorpyrifos and fungicide carbendazim, common food contaminants mixture, induce hepatic, renal, and splenic oxidative damage in female rats.

The fungicide carbendazim (CBZ) and insecticide chlorpyrifos (CPF) are currently applied together by farmers for the control of pests. Here, we investigated the impacts of 7 days oral co-exposure to 10 mg/kg body weight of CPF and 50 mg/kg body weight of CBZ on selected oxidative stress and antioxidant biomarkers in the liver, kidney, and spleen of female rats. The results showed that while the body weight gain and relative organ weights were not significantly affected after separate exposure to CPF and CBZ, there was a significant decrease in the body weight gain with concomitant increases in the relative kidney and spleen weights of rats treated with the mixture. Also, CPF and CBZ co-exposure significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine ( p < 0.05) when compared with the groups treated with CBZ or CPF alone and the control. The significant decreases in both antioxidant enzymes activities and nonenzymatic antioxidant level following individual administration of CPF and CBZ to rats were intensified in the co-exposure group ( p < 0.05). Additionally, the marked increases in the levels of oxidative stress indices in liver, kidney, and spleen of rats treated with CPF or CBZ alone were intensified in the co-exposure group ( p < 0.05). Histopathologically, co-exposure to CPF and CBZ exacerbates their individual effects on the liver, kidney, and spleen. These findings showed that co-exposure to CPF and CBZ in rats elicited more severe oxidative damage on the liver, kidney, and spleen of the rats, indicative of an additive effect compared to CPF or CBZ alone and as such, may pose a greater environmental risk to humans.

Endocrine disruption and oxidative stress implications of artemether-lumefantrine combination therapy in the ovary and uterus of rats.

In the current study, we evaluated the endocrine disruption effect and oxidative stress implication of therapeutic dose of artemether-lumefantrine combination therapy on the ovary and uterus of rats. In this respect, female rats were divided into four groups: animals were per orally treated with tween 80 (control), artemether (4 mg kg-1 body weight), lumefantrine (24 mg kg-1 body weight) and artemether-lumefantrine (artemether, 4 mg kg-1 body weight and lumefantrine, 24 mg kg-1 body weight). We found that therapeutic doses of the drugs did not change the levels of ovarian hydrogen peroxide (H2O2) and malondialdehyde (MDA), but increased uterine levels of H2O2 and MDA and reduced ovarian and uterine levels of reduced glutathione. In addition, whilst ovarian glutathione peroxidase (GPx) activity reduced in the lumefantrine monotherapy group, uterine GPx increased in the artemether monotherapy as well as the artemether-lumefantrine groups. Furthermore, the drugs reduced ovarian and uterine glutathione- S-transferase and uterine superoxide dismutase activities. The drugs reduced oestrogen level, whereas follicle-stimulating hormone was reduced by lumefantrine and artemether-lumefantrine therapies. Additionally, artemether and lumefantrine monotherapies significantly increased prolactin and progesterone levels compared with the control ( p < 0.05). The results suggest that in the absence of malarial parasite infection, the drugs induced oxidative stress in the ovary and uterus and disrupt hormonal balance in the rats.

Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes and uterus but not in the ovary of rats.

Artemisinin is an antimalarial drug previously reported to induce neurotoxicity and embryotoxicity in animal models. This study investigated the erythrocytes and reproductive toxicity potentials of artemisinin in female rats. Animals were randomly divided into four study groups of eight rats each. The control group (group I) received corn oil, the vehicle, while groups II-IV were orally exposed to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric intubation for 7 consecutive days. Subsequently, we evaluated the impact of artemisinin on the endocrine environment and selected markers of oxidative damage and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and decreased catalase, glutathione peroxidase and superoxide dismutase activities in erythrocytes and uterus of rats compared with control group (p < 0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels and catalase activity, while ovarian and uterine histological assessment revealed absence of visible lesions. Moreover, artemisinin significantly decreased follicle-stimulating hormone and increased progesterone levels compared with control (p < 0.05). Thus, these data suggest that in the absence of malarial parasite infection, artemisinin induced hormonal imbalance and oxidative damage in the erythrocytes and uterus but spared the ovary of rats.

Particles internalization, oxidative stress, apoptosis and pro-inflammatory cytokines in alveolar macrophages exposed to cement dust.

Exposure to cement dust is one of the most common occupational dust exposures worldwide, but the mechanism of toxicity has not been fully elucidated. Cement dust (N) and clinker (C) samples collected from Nigeria and another sample of cement dust (U) collected from USA were evaluated using alveolar macrophage (NR8383) cell culture to determine the contribution of different sources of cement dust in the severity of cement dust toxicity. Cement dust particles internalization and morphologic alterations using transmission electron microscopy (TEM), cytotoxicity, apoptotic cells induction, intracellular reactive oxygen species generation, glutathione reduction, TNF-α, IL-1ß, and CINC-3 secretion in alveolar macrophages (NR8383) exposed to cement dust and clinker samples were determined. Particles were internalized into the cytoplasmic vacuoles, with cells exposed to U showing increased cell membrane blebbing. Also, NR8383 exposed to U show more significant ROS generation, apoptotic cells induction and decreased glutathione. Interleukin-1ß and TNF-α secretion were significantly more in cells exposed to both cement dust samples compared with clinker, while CINC-3 secretion was significantly more in cells exposed to clinker (p < 0.05). Endocytosis, oxidative stress induced-apoptosis and induction of pro-inflammatory cytokines may be key mechanisms of cement dust immunotoxicity in the lung and toxicity may be factory dependent.

AN INVESTIGATION INTO THE ANTIMALARIAL EFFECT OF METHANOLIC EXTRACT OF PAULLINIA PINNATA LEAVES IN PLASMODIUM BERGHEI INFECTED MICE AND COURSE OF INFECTION.

AIM: The aim of this study was to investigate the antimalarial activity of methanolic leaves extract of Paullinia pinnata on chloroquine-sensitive Plasmodium berghei NK 65 infected mice. METHODOLOGY: The curative study was conducted in thirty-six Wistar albino mice of both sexes which were divided into six groups of six animals each. The animals were infected with P. berghei NK 65. Group I was the negative control and received the vehicle (10% DMSO). Group II received no treatment. Groups III and IV were the positive controls and received chloroquine (CQ) (10mg/kg) and artesunate (4 mg/kg)-amodiaquine (10mg/kg) combination (ACT) respectively. Groups V and VI received 100mg/kg and 200mg/kg doses of the extract respectively. Administration was done orally once for three or four days for the standard drugs or the extract/vehicle respectively. The percentage parasitaemia, packed cell volume (PCV), body weight and death was monitored on days 0, 1, 2, 3, 4 and 11 (7 day post administration). The study of the course of infection of P. berghei was monitored in eighteen Wistar albino mice of both sexes which were similarly grouped, infected and treated for 3 days. Group A received the vehicle (distilled water) only. Group B was treated with CQ (10 mg/kg) and Group C with ACT. The percentage parasitaemia and death was monitored from day 0 to day 30 (27 day post administration). RESULTS: In the curative study, the extract suppressed parasitaemia at both doses on day 4. The group treated with 200mg/kg dose showed a higher percentage chemosuppression though not significant. The course of infection study revealed that recrudescence occurred on day 8 in the CQ treated group which lasted until day 23 after which the recrudescence was lost without re-treatment. A similar result was observed in the ACT group. CONCLUSION: The methanolic leaves extract of Paullinia pinnata has weak anti-malarial property. Chloroquine-sensitive P. berghei NK65 loses credibility and needs to be revalidated biannually.

Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin.

The indiscriminate use, abuse and patients' noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.

Kolaviron protects against ethylene glycol monoethyl ether-induced toxicity in boar spermatozoa.

This study investigated the ameliorative effects of kolaviron (a biflavonoid from the seed of Garcinia kola) and vitamin C on ethylene glycol monoethyl ether (EGEE)-induced oxidative damage in boar spermatozoa in vitro. EGEE (1.0 mm) was incubated with boar spermatozoa for 3 h with or without either kolaviron (50 and 100 µm) or vitamin C (1.0 mm). Spermatozoa parameters were determined hourly during the incubation period, whereas aminotransferases and alkaline phosphatase activities and oxidative stress indices were assessed after the incubation period. Results showed a time-dependent decline in spermatozoa motility and viability with significant elevation in total abnormalities in EGEE-treated spermatozoa. Exposure to EGEE resulted in significant increase in aminotransferases, alkaline phosphatase and superoxide dismutase (SOD) activities, whereas it markedly decreased glutathione (GSH) level, catalase (CAT) and glutathione S-transferase (GST) activities with concomitant increase in hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA) levels. Pre-treatment of spermatozoa with kolaviron or vitamin C significantly decreased H2 O2 and MDA levels, improved spermatozoa characteristics and ameliorated oxidative damage in EGEE-treated spermatozoa. Taken together, EGEE exhibited its spermatotoxicity via induction of oxidative stress. The protective effects by kolaviron and vitamin C against EGEE-induced oxidative damage may be due to their intrinsic antioxidative potentials.

In Vitro Antioxidant Properties of Methanolic Leaf Extract of Vernonia Amygdalina Del.

Various methods employed in evaluating antioxidant activities of various samples gives varying results depending on the specificity of the free radical or oxidant used as a reactant. This study investigated the antioxidant /radical scavenging properties of the methanolic extract of Vernonia amygdalina (MEVA) leaves and studied the relationship between the assay methods. Antioxidant capacity of MEVA was evaluated by measuring the radical scavenging activity (RSA) of MEVA on 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), nitric oxide (NO) and hydrogen peroxide (HP), hydroxyl radical (OH•) scavenging activity (HRSA), lipid peroxidation inhibition activity (LPIA) against 2,2,-azobis(2-amidinopropane) hydrochloride (AAPH) and Trolox Equivalent Antioxidant Capacity (TEAC) of MEVA against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) radicals as well as the reducing power (RP). Assay methods were subjected to regression analysis and their correlation coefficients calculated. Results were analysed using student?s t-test and ANOVA. MEVA exhibited highest percentage RSA of 85.8% on HP, followed by DPPH• (29.6%), OH• (26.4%) and least on NO• (21.8%). MEVA inhibited AAPH-induced lipid peroxidation by 30.0% and ABTS-induced radical by 1489% with a marked RP of 0.242±0.01. DPPH correlated excellently with RP (r2 = 0.86), TEAC (r2 = 0.94) and HRSA (r2 = 0.89), the four having good relationship with each other, while LPIA correlated moderately with HP (r2 = 0.48 and NO (r2 = 0.34). MEVA exhibited significant free radical scavenging and antioxidant activities. The assay methods correlates very well and could therefore be employed for investigating and understanding antioxidant properties and scavenging activities of plant materials.

Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats.

The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200mg/kg) singly or in combination with kolaviron (100 and 200mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.

Lead, mercury, cadmium, chromium, nickel, copper, zinc, calcium, iron, manganese and chromium (VI) levels in Nigeria and United States of America cement dust.

This study was aimed at investigating the relative abundance of heavy metals in cement dust from different cement dust factories in order to predict their possible roles in the severity of cement dust toxicity. The concentrations of total mercury (Hg), copper (Cu), chromium (Cr), cadmium (Cd), nickel (Ni), manganese (Mn), lead (Pb), iron (Fe) and chromium (VI) (Cr (VI)) levels in cement dust and clinker samples from Nigeria and cement dust sample from the United States of America (USA) were determined using graphite furnace atomic absorption (GFAAS), while Zn and Ca were measured by flame atomic absorption spectrophotometry (FAAS), and Cr (VI) by colorimetric method. Total Cu, Ni and Mn were significantly higher in cement dust sample from USA (p<0.05), also, both total Cr and Cr (VI) were 5.4-26 folds higher in USA cement dust compared with Nigeria cement dust or clinker (p<0.001). Total Cd was higher in both Nigeria cement dust and clinker (p<0.05 and p<0.001), respectively. Mercury was more in both Nigeria cement dust and clinker (p<0.05), while Pb was only significantly higher in clinker from Nigeria (p<0.001). These results show that cement dust contain mixture of metals that are known human carcinogens and also have been implicated in other debilitating health conditions. Additionally, it revealed that metal content concentrations are factory dependent. This study appears to indicate the need for additional human studies relating the toxicity of these metals and their health impacts on cement factory workers.

Chemoprotective effects of kolaviron on ethylene glycol monoethyl ether-induced pituitary-thyroid axis toxicity in male rats.

Endocrine disrupting chemicals cause reproductive dysfunction by interacting with intricate regulation and cellular processes involve in spermatogenesis. This study investigated the probable mechanism of action of ethylene glycol monoethyl ether (EGEE) as an antiandrogenic compound as well as the effects of kolaviron upon co-administration with EGEE in rats. Adult male rats were exposed to EGEE (200 mg kg(-1) bw) separately or in combination with either kolaviron [100 (KV1) and 200 (KV2) mg kg(-1) bw] or vitamin E (50 mg kg(-1) bw) for 14 days. Western blot analysis revealed that the administration of EGEE adversely affected steroidogenesis in experimental rats by decreasing the expression of steroid acute regulatory (StAR) protein and androgen-binding protein (ABP). EGEE significantly decreased the activities of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) but markedly increased sialic acid concentration in rat testes. EGEE-treated rats showed significant decreases in plasma levels of luteinising hormone (31%), testosterone (57.1%), prolactin (80.9%), triiodothyronine (65.3%) and thyroxine (41.4%), whereas follicle-stimulating hormone was significantly elevated by 76.9% compared to the control. However, co-administration of kolaviron or vitamin E significantly reversed the EGEE-induced steroidogenic dysfunction in rats. This study suggests that kolaviron may prove promising as a chemoprotective agent against endocrine pathology resulting from EGEE exposure.

Quercetin exacerbates the effects of subacute treatment of atrazine on reproductive tissue antioxidant defence system, lipid peroxidation and sperm quality in rats.

The study investigated the reproductive function and the antioxidant defence system of rats co-exposed to atrazine [ATZ, 120 mg kg(-1) body weight (b. wt)] and quercetin (QT, 20 mg kg(-1) b. wt.). ATZ had no significant effects on feed intake, body weights and reproductive organs weight except prostate weight. Sperm abnormalities were increased, whereas sperm production, sperm motility and epididymal and testicular sperm numbers were decreased with ATZ treatment. Antioxidant enzymes including superoxide dismutase, glutathione-S-transferase and glutathione peroxidase were significantly altered in the epididymis and testis resulting to lipid peroxidation. A potentiating response on glutathione-S-transferase and aspartate aminotransferase activities in the testis and on lactate dehydrogenase activity and glutathione level in the epididymis was observed in the QT + ATZ animals. Quercetin alone decreased seminal vesicle and prostate weights, increased superoxide dismutase activity in the testis and ascorbate level in the epididymis. Mild pathological changes were observed in the ATZ group, whereas considerable necrosis of seminiferous tubular cells with hypoplasia of the epithelia was observed in the QT + ATZ animals. The epididymis of these animals had multilayered and sometimes a single lining epididymal epithelium with few spermatozoa. We conclude that quercetin at the investigated dose increases the susceptibility of rat reproductive tissues to atrazine-induced oxidative damage.

The protective effects of quercetin on the cytotoxicity of atrazine on rat Sertoli-germ cell co-culture.

To evaluate the direct effect of atrazine (ATZ) and the protective effect of quercetin (QT) on testicular cells, we used primary cultures of rat Sertoli-germ cells (SGCs). ATZ (232 µm) up-regulated the mRNA expression of GATA-4, androgen receptor (AR), androgen-binding protein (ABP), steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (CYP11A1), cyclooxygenase-2 (COX-2) and NF-κappaB (NF-κB) and down-regulated the expression of stem cell factor (SCF) mRNA. There was no change on the mRNA expression of oestrogen receptor-alpha (ER-α). Simultaneous supplementation of QT in the culture normalizes the expression of these genes. The stimulatory action of follicle stimulating hormone (10 ng/mL) on ATZ-induced StAR and CYP11A1 mRNA levels were also prevented by QT. Furthermore, ATZ-stimulatory action on AR mRNA was opposed in a dose-dependent manner in the presence of increasing concentrations of QT (10-50 µm).The dislodgement of germ cells from the Sertoli cells monolayer and decrease in SGCs viability was prevented by QT. To show whether or not the disrupted interactions of Sertoli and germ cells impaired spermatogenesis, adult male rats exposed in vivo to ATZ (50 mg/kg b.wt) for 1 week had their daily spermatozoa production (DSP) per gram testis lowered by 30%. DSP was significantly increased in the QT(10 mg/kg) + ATZ-treated rats as compared with the ATZ-treated rats. Taken together, ATZ can alter SGCs expression of spermatogenesis- and steroiodogenesis-related genes resulting in a decrease in sperm production in the testis as well as cell viability. QT might block these molecular events-induced by ATZ thereby protecting testicular Sertoli-germ cells from ATZ-induced toxicity.

Protective effects of kolaviron and quercetin on cadmium-induced testicular damage and endocrine pathology in rats.

This study evaluated the effects of kolaviron, a biflavonoid from Garcinia kola seed, and quercetin on cadmium-induced reproductive toxicity in rats. Adult male rats were administered with either cadmium (15 mg kg(-1)) alone or in combination with kolaviron (200 mg kg(-1)) or quercetin (10 mg kg(-1)) daily for 5 days. Cadmium-treated rats showed (P < 0.05) decrease in the body weight gain, testis and epididymis weights. However, upon co-administration of kolaviron or quercetin, these changes were significantly reversed in cadmium-treated rats. Also, administration of kolaviron or quercetin significantly prevented cadmium-mediated decrease in sperm motility and epididymal sperm concentration and reversed the increased level of sperm abnormality to near control. In testes and sperm, cadmium treatment resulted in significant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase, whereas it increased glutathione S-transferase activity as well as hydrogen peroxide and malondialdehyde levels. While plasma levels of triiodothyronine and tetraiodothyronine remained unaffected, the levels of testosterone, luteinising hormone and follicle stimulating hormone were decreased in cadmium-treated rats. Cadmium treatment caused mild congestion of interstitial vessels and oedema in the testes. Taken together, kolaviron and quercetin inhibited the adverse effects of cadmium on the antioxidant enzymes, markers of oxidative stress, endocrine and testicular structure in rats.