CP-induced Reproductive Toxicity Research Articles

Lecithin’s antioxidant properties protect against cyclophosphamide-induced reproductive toxicity and infertility in male rats

Background: Infertility is a prevalent problem that affects 15% of couples globally. Male infertility, which accounts for half of all cases, can be caused by several factors, including aging, drug use, genetic problems, and exposure to environmental toxins. Cyclophosphamide (CP) is a commonly utilized immunosuppressant and anticancer medication that can induce oxidative stress and harm the reproductive system of men. The beneficial effects of antioxidants in mitigating the CP-induced reproductive toxicities are well-documented. Aim: The aim of this study was to assess the effects of lecithin (as an antioxidant) against the CP-induced reproductive toxicity in male rats. Methodology: Thirty Sprague-Dawley male rats were divided into three groups: (i) the negative control group (that received sterile water via the intragastric route for 13 consecutive days), (ii) the positive control group (that received sterile water via the intragastric route for 5 days and, subsequently, a single, intraperitoneal dose of CP on day 6, followed by sterile water via the intragastric route for the next 7 consecutive days), and (iii) the lecithin-treated group (that received lecithin via the intragastric route for 5 days and, subsequently, a single, intraperitoneal dose of CP on day 6, followed by lecithin via the intragastric route for the next 7 consecutive days). Results: Lecithin treatment improved sperm parameters, plasmatic testosterone levels, and glutathione peroxidase, thereby preventing histopathological alterations in the rat testes. Conclusion: Lecithin demonstrated its potential protective effects against reproductive impairments and oxidative stress in the CP-treated rat group, and might prove promising for use in clinical practice as a protective agent against chemotherapy-induced male reproductive toxicity and infertility.

Nme8 is essential for protection against chemotherapy drug cisplatin-induced male reproductive toxicity in mice.

Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6-7 of the Nme8 in mice based on human mutation sites and observed impaired transcript splicing. In mice, Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. Nme8 expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients.

Evaluation of the therapeutic effects of arbutin on cisplatin‐induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.

Effect of cashew (Anacardium occidentale L.) nut-supplemented diet on steroidogenic enzymes, hormonal and oxidative imbalances, and sperm parameters in cisplatin-induced reproductive toxicity in male rats.

Cisplatin (CP) is a chemotherapeutic/anticancer drug culpable in sperm and testicular damage, but the use of dietary patterns has been reported to averse this effect. To date, no report on the use of roasted cashew nut-supplemented diets (RCNSD) against chemotherapy-induced testicular damage has been presented. In this study, the effect of 10% and 20% RCNSD on reproductive hormones, sperm parameters, testicular and epididymal antioxidant status, and steroidogenic enzymes activities in CP-induced rats were determined. Interestingly, these parameters were boosted, but with a decrement in radical species level in the testes/epididymis of CP-induced rats fed with RCNSD as against the untreated CP-induced rats. The modulatory effect of RCNSD on the tested reproductive parameters in studied tissues could be among the mechanism of action, by which RCNSD mitigates andrological toxicity. Hence, RCNSD could be harnessed as a functional food/nutraceutical agent for alleviating the andrological toxicity of CP-induced male reproduction. PRACTICAL APPLICATIONS: Consumption of cashew nuts has been a great benefit to human health, as a result of its richness in nutritional constituents including biologically active amino acids, tocopherols, fatty acids, polyphenols, and selenium, among others. Cashew nuts are mostly consumed fried/roasted, with yoghurt, as a paste, or used as an ingredient in confectionery products. The folkloric use of cashew nuts in the management of cardiovascular diseases, male reproductive disorders, and diabetes has been reported. In this study, the ability of roasted cashew nut-supplemented diets to modulate reproductive hormones, sperm parameters, testicular and epididymal antioxidant status, and steroidogenic enzymes activities in CP-induced reproductive toxicity in male rats was revealed, thus, indicating its possible use, clinically, in the management of reproductive toxicity induced by cancer drugs.

Ameliorative effect of Allium atroviolaceum on sperm quality in cyclophosphamide-treated mice

BackgroundCyclophosphamide (CP) is an anti-neoplastic alkylating agent that is extensively used in different chemotherapy regimens. Adverse effects on the reproductive system, especially spermatogenesis, are one of the most important side effects of this drug. It is medically essential to use complementary and alternative drugs. Herbal drugs have long been used as a complementary treatment. Our purpose was to study the effect of hydroalcoholic Allium atroviolaceum L. extract on spermatogenesis in CP-treated mice.ResultsCP affected a significant decrease in sperm count, motility, viability, and morphology. Sperm count was significantly higher in the all extract groups than in the group of control (p<0.001) and CP group (p<0.001, p<0.01). Sperm motility was significantly greater in the extract (100 and 200mg/kg) groups than in the group of control (p<0.05 and <0.001). Sperm immotility and rotational movement were significantly higher in the CP group than in the CP+extract groups (p<0.001). The sperm viability was significantly greater in the CP+extract (200mg/kg) group than in the CP group (p<0.001). The number of headless sperm, sperm with initial tail, with coiled tail, and sperm with curved body, was significantly lower in the CP+extract (200mg/kg) group than in the CP group (p<0.001).ConclusionA. atroviolaceum extract treatment significantly improved CP-induced reproductive toxicity.

Network pharmacology reveals pharmacological effect and mechanism of Panax notoginseng (Burk.) F. H. Chen on reproductive and genetic toxicity in male mice

Ethnopharmacological relevanceCisplatin (CP), one of the most commonly used antitumor drugs in clinic, could induce reproductive and genetic toxicity. Traditional Chinese medicine believed that this side effect might be caused by the deficiency of both qi and blood. Panax notoginseng (Burk.) F. H. Chen (PN) is a traditional precious Chinese medicine for nourishing blood and hemostasis, which had the synergistic antitumor and reducing toxicity effects. However, the protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity were still unknown.Aim of the study: This study was designed to illuminate the possible protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity. Materials and methodsNetwork pharmacology was first applied to analyze the potential components and targets of PN against CP-induced reproductive and genetic toxicity. Then, the results of network pharmacology were validated in a mouse model of reproductive and genotoxicity induced by CP. Body weight, testis weight, epididymis weight, sperm count, sperm viability and sperm morphology were used to assess protective effects of PN on CP-induced reproductive toxicity. Tail moment in peripheral blood cells and micronucleus in bone marrow cells were used to assess protective effects of PN on CP-induced genetic toxicity. Finally, possible protective targets obtained from network pharmacology, including 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), were experimentally validated by ELISA. ResultsOne hundred and nineteen components of PN and sixty-eight targets of reproductive/genetic toxicity were acquired and constituted as the component-target network. Network pharmacology analysis showed alleviating oxidative stress might play important role in therapeutic mechanism of PN. In verified experiments, PN significantly improved the decline of body weight, testis weight and epididymis weight, increased sperm count and viability, decreased abnormal sperm morphology rate induced by CP in mice. Moreover, PN also significantly decreased the tail moment in peripheral blood cells and micronucleus formation rate in bone marrow cells in CP-induced mice. Finally, not only the decrease of T-SOD and GSH-Px level but also the increase of 8-OHdG and MDA level in serum were restored under PN treatment. ConclusionCurrent study found that PN could improve CP-induced reproductive and genetic toxicity, which were probably attributed to alleviating oxidative stress. This finding provided the new perspective for understanding the therapeutic effect of PN on CP-induced reproductive and genetic toxicity and facilitating the clinical use of PN.

Protective effect of Liuwei Dihuang Pill on cisplatin-induced reproductive toxicity and genotoxicity in male mice.

Cisplatin (CP) is the classical chemotherapeutic drug for various cancer, but it also accompanies reproductive toxicity and genotoxicity. Liuwei Dihuang Pill (LW) is the traditional Chinese medicine prescription for treating Kidney-Yin deficiency syndrome, which has been reported to prevent and treat various diseases. However, the protective effect of LW on CP-induced reproductive toxicity and genotoxicity has not been reported. To investigate the potential protective effect and mechanism of LW on CP-induced reproductive toxicity and genotoxicity in male mice. Mice were given LW (0.4, 1.2 and 3.6 g/kg) or Vitamin C (0.1 g/kg) once daily by oral gavage for thirteen consecutive days. Then, CP (3.00 mg/kg) was given intraperitoneal injection once daily for five consecutive days starting on the ninth day. The protective effects of LW against CP-induced reproductive toxicity and genotoxicity were evaluated by body weight, testis ratio, sperm count, sperm viability, sperm abnormal morphology type, micronuclei test, testicular histopathology, serum malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) level. The results demonstrated that LW could significantly increase CP-induced the reduction of sperm count and sperm viability, then decrease abnormal sperm type rate and micronucleus rate. Moreover, LW also could improve testicular abnormal histopathologic morphology induced by CP exposure. Meanwhile, LW decreased serum MDA level and increased T-SOD, GSH-Px and CAT level compared to CP group. our findings show that LW has protective effects on CP-induced reproductive toxicity and genotoxicity. LW decreases serum MDA level and increases T-SOD, GSH-Px and CAT level, which indicates that antioxidant activity may be the potential mechanism of LW to resist reproductive toxicity and genotoxicity.

PROTECTIVE EFFECT OF L-CARNITINE AND VITAMIN E ON CYCLOPHOSPHAMIDE INDUCED TOXICITY ON RAT TESTES

Background: Cyclophosphamide (CP) was a chemotherapeutic agent, known to cause male reproductive toxicity. Some antioxidant agents were found protective against CP toxicity e.g L-Carnitine and Vitamin E. L-carnitine (LC) was commonly used in treatment of male infertility. While Vitamin E (Vit E) was an essential nutrient for reproduction. Aim of the work: This study was designed to assess, by anatomical and histological examination, the possible protective effects of LC and Vit E on the testes of CP treated albino rats. Material and Methods: Rats were categorized into: Control group I (GP Ia receiving intraperitoneal saline, gp Ib and gp Ic receiving LC and Vit respectively), experimental group II receives intraperitoneal CP, and Protected group III (GP IIIa, GP IIIb receiving CP with LC and Vit E respectively). After two weeks, the rats were sacrificed, testes were dissected, and examined grossly then histologically using light and Electron microscopy. Results: GP II showed a significant reduction in the mean value of the testicular weight and dimensions in comparison with GP I. The mean value for GP IIIa and IIIB was significantly increased in comparison with GP II. Histological changes in GP II revealed intracellular vacuolization and sloughing of the spermatogonial cells. Decreased number of sperms was encountered. Both GP IIIa and GP IIIB showed improvement. However, Gp IIIa was better than Gp IIIb. Conclusion: LC and Vit E could be used as protective agents against CP-induced reproductive toxicity, but the protective effect of LC was better than Vit E.

Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats

ObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats. MethodsIn addition to a normal control (group 1), drugs or vehicles were administered orally to seven groups (n = 5) of rats that had already received 4-weeks of pre-treatment with CP (5 mg/[kg·d], per oral administration); group 2 received CP + distilled water (10 mL/[kg·d]); group 3 received CP + 5% tween 80 (10 mL/[kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/[kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/[kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/[kg·d]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated. ResultsThe CP-treated group showed a significant reduction (P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated (P < 0.001) sperm morphological abnormalities and testicular structure alterations, compared to the control group. Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts. For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count (P < 0.001), sperm motility (AE, 50 mg/kg, P < 0.05; ME, 50 and 100 mg/kg, P < 0.05) and sperm viability (AE, 50 mg/kg, P < 0.001; ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes. ConclusionH. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.

Ameliorative Effect of Carvacrol on Cisplatin-Induced Reproductive Damage in Male Rats.

Cisplatin (CP) treatment causes the damage in male reproductive system. Carvacrol (CARV) is an antioxidant that is naturally found in some plants. We aimed to investigate the effect of CARV on CP-induced reproductive toxicity in male rats. Eighteen adult male Sprague-Dawley rats were used. The controlgroup (n = 6) was treated orally with physiological saline (PS) daily for 14 days and a singleintraperitoneal (IP) PS injection on day 10. The CP group (n = 6) was administered with daily oral PS for 14 daysand a single IP injection of 10 mg/kg CP on day 10. The CARV + CP group(n = 6) was treated with daily 75 mg/kg oral CARV for 14 days and a single IP injection of 10 mg/kg CP on day 10. CP treatment caused the damage on some spermatological parameters (motility, live sperm rate, and abnormal sperm rate), increased the oxidative stress, and induced testicular degeneration and apoptosis. However, CARV treatment mitigates CP-induced reproductive toxicity.

Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats.

Cisplatin (CP) treatment causes damage in the male reproductive system. Rutin (RUT) is a naturally occurring flavonoid glycoside that has antioxidant and anti-inflammatory properties. This study aimed to investigate effects of RUT against cisplatin-induced reproductive toxicity in male rats. Twenty-one adult male Sprague Dawley rats were used. The control group received physiological saline with oral gavage during 14days, and physiological saline was injected intraperitoneally (IP) in 10th days of study. CP Group received physiological saline during 14days, and 10mgkg-1 CP was injected IP in 10th day. RUT+CP group received RUT (150mgkg-1 ) during 14days, and 10mgkg-1 CP was injected IP in 10th day. Spermatological parameters (including motility, cauda epididymal sperm density, dead sperm percentage and morphological sperm abnormalities), biochemical (MDA, GSH, GSH-px, SOD and CAT), histological (H&E dye) and immunochemistry evaluations of testicles were evaluated. CP treatment caused damage on some spermatological parameters, increased the oxidative stress and induced testicular degeneration and apoptosis when compared to the control group. However, RUT treatment mitigates these side effects when compared to the CP alone group. IT is concluded that RUT treatment may reduce CP-induced reproductive toxicity as a potential antioxidant compound.

Neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn.) leaf in male Wistar rat model of cyclophosphamide-induced reproductive toxicity.

Cyclophosphamide (CP) is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn.) leaf (AEAVL) in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E) groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days) as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days) were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05) following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity.

Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide.

Reproductive toxicity is one of the side effects of cyclophosphamide (CP) in cancer treatment. Pumpkin seeds and Zingiber officinale are natural sources of antioxidants. We investigated the possible protective effect of combined pumpkin seed and Zingiber officinale extracts on sperm characteristics, epididymal histology and biochemical parameters of CP-treated rats. Male adult Wistar rats were divided randomly into six groups. Group 1, as a control, received an isotonic saline solution injection intraperitoneally (IP). Group 2 were injected IP with a single dose of CP (100mg/kg) once. Groups 3 and 4 received CP plus 300 and 600mg/kg combined pumpkin seed and Zingiber officinale extract (50:50). Groups 5 and 6 received only 300 and 600mg/kg combined pumpkin seed and Zingiber officinale extract. Six weeks after treatment, sperm characteristics, histopathological changes and biochemical parameters were assessed. In CP-treated rats, motile spermatozoa were decreased, and abnormal or dead spermatozoa increased significantly (P<0.001) but administration of the mixed extract improved sperm parameters. Epididymal epithelium and fibromascular thickness were also improved in extract-treated rats compared to control or CP groups. Biochemical analysis showed that the administration of combined extracts could increase the total antioxidant capacity (TAC) level significantly in groups 3, 4, 5 and 6. Interestingly, the mixed extract could decrease most of the side effects of CP such as vacuolization and separation of epididymal tissue. Our findings indicated that the combined extracts might be used as a protective agent against CP-induced reproductive toxicity.

Protective effect of Pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with Cyclophosphamide

Cancer treatment with cyclophosphamide (CP) may result in reproductive toxicity as one of its side effects. The pumpkin seed is a rich natural source of antioxidant. We have assessed the possible protective efficacy of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology of CP-treated rats. Male adult Wistar rats were categorised into four groups. Group 1 served as control and received intraperitoneal (IP) injection of isotonic saline solution. Group 2 rats were treated with CP by IP injection in a single dose of 100 mg/kg body weight, only once. Group 3 and 4 received CP plus 300 and 600 mg/kg pumpkin seed extract respectively. Six weeks after treatment, sperm characteristics, biochemical parameters and histopathological changes were examined. Results showed that, sperm characteristics in CP-treated rats were significantly decreased. Biochemical analysis results showed that the co-administration of 300 mg pumpkin seed extract could increase the total antioxidant capacity (TAC) level significantly. In CP-treated rats, histopathological changes such as vacuolisation, disorganisation and separation of epididymal epithelium were observed as well. Interestingly, pumpkin seed extract could improve the above-mentioned parameters remarkably in CP-treated rats. Our findings indicated that pumpkin seed extract might be used as protective agent against CP-induced reproductive toxicity.

Beneficial effects of &amp;lt;i&amp;gt;Achillea millefolium&amp;lt;/i&amp;gt; aqueos extract against cyclophosphamide-induced reproductive toxicity

Objective: Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Achillea millefolium, a widely distributed medicinal plant, is highly regarded for its medicinal activities, including antioxidant and anti-inflammatory properties. The present study was conducted to assess whether Achillea millefolium inflorescences aqueous extract could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Methods: Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg/kg-BW/day for 28 days by oral gavages. One of these groups received Achillea millefolium aqueous extract at a dose of 1.2 g/kg-BW/day orally four hours after cyclophosphamide administration. A vehicle treated control group and an A.millefolium control group were also included. Results: The CP-treated group showed significant decreases in the body and reproductive organs weights as well as sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK and SGOT were observed in CP-treated rats. Notably, A.millefolium aqueous extract co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicate that A.millefolium may be partially protective against CP-induced reproductive toxicity.

Astragalus membranaceus Ameliorates Reproductive Toxicity Induced by Cyclophosphamide in Male Mice

The root of Astragalus membranaceus B(UNGE) (AM) is a medicinal herb that has been capable of reducing the adverse effects of conventional chemotherapy. To investigate the effects of AM on cyclophosphamide (CP)-induced reproductive toxicity in mouse testes, 5-week-old male imprinting control region mice were divided into five groups; CP was treated on the first day of each week for 5 weeks (100 mg/kg, i.p.), and AM was treated for 5 days a week for 5 weeks. At the end of the treatment period, the testes were taken out, cleared of the adhering tissues, and weighed. Epididymis was taken out and used for sperm analysis. Testis samples were frozen for real-time quantitative PCR and Western blot analysis. AM treatment increased diminished relative testes weight, and sperm count and motility in mice treated with CP. CP treatment has detrimental effects on the expression of cAMP-responsive element modulator (CREM), a transcription factor that is highly expressed in male germ cells and is crucial to post-meiotic germ cell differentiation. AM restored CREM at both the mRNA and protein levels. AM has beneficial influences and appears able to ameliorate relative testes weight, sperm parameters, and CREM expression against CP-induced reproductive toxicity.

102-MARITAL STRESS AS AN INDEPENDENT FACTOR OF HYPERTENSION

Cyclophosphamide (CP) is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn.) leaf (AEAVL) in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E) groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days) as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days) were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05) following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity.