RESUMEN
Calliandra portoricensis (C. portoricensis) is used in herbal homes in Nigeria to manage breast diseases. We investigated the anti-tumourigenic effects of chloroform extract of C. portoricensis (CP) in breast experimental cancer induced by N-methyl-N-nitrosourea (NMU) and benzo-(a)-pyrene (BaP). Fifty-six female rats were assigned into seven equal groups: Group 1 served as control, group 2 received NMU and BaP (50 mg/kg, each), groups 3 and 4 received [NMU + BaP] and treated with CP at 50 and 100 mg/kg, respectively. Group 5 received CP (100 mg/kg), group 6 received [NMU + BaP] and vincristine (0.5 mg/kg), while group 7 received vincristine (0.5 mg/kg). The NMU and BaP (i.p) were dissolved in normal saline and corn oil, respectively. The CP (oral) and vincristine (i.p) were given thrice and twice per week, respectively for 10 weeks. The [NMU + BaP] intoxication significantly decreased body weight gain by 32% while organo-somatic weight of mammary gland increased by 37%. Also, [NMU + BaP] decreased the activities of mammary catalase, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase and total sulphurhydryl by 34%, 31%, 35%, 35% and 33%, respectively. The [NMU + BaP] increased inflammatory and oxidative stress markers; nitrite, lipid peroxidation and myeloperoxidase by 62%, 57% and 361%, respectively. Strong expression of BCL-2, IL-6, COX 2, ß-catenin and iNOS in [NMU + BaP]-administered rats were observed. Histology revealed glands with malignant epithelial cells and high nucleocytoplasm in [NMU + BaP] rats. Treatment with CP attenuated inflammation, apoptosis and restored cyto-architecture of mammary gland. Overall, CP abates mammary tumourigenesis by targeting cellular pathways of inflammation and apoptosis.
Asunto(s)
Metilnitrosourea , Neoplasias , Extractos Vegetales , Animales , Femenino , Ratas , Benzo(a)pireno/toxicidad , beta Catenina , Carcinogénesis , Catalasa/metabolismo , Cloroformo , Ciclooxigenasa 2 , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Inflamación , Interleucina-6 , Metilnitrosourea/toxicidad , Nitritos , Peroxidasa , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-bcl-2 , Superóxido Dismutasa/metabolismo , Vincristina , Fabaceae/químicaRESUMEN
Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC50 of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.
Asunto(s)
Clusiaceae , Garcinia kola , Albúminas/metabolismo , Albúminas/farmacología , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Cisplatino/toxicidad , Clusiaceae/metabolismo , Aceite de Maíz/farmacología , Creatinina , Garcinia kola/metabolismo , Glutatión/metabolismo , Hexanos/farmacología , Peroxidación de Lípido , Masculino , Ratones , Estrés Oxidativo , Extractos Vegetales/farmacología , Quercetina/farmacología , Semillas , Superóxido Dismutasa/metabolismoRESUMEN
IMPACT STATEMENT: Infertility resulting from reproductive impairment is traumatic in families. Exposure to chemicals may play insidious roles not easily connected to infertility. We examined benzo[a]pyrene (BaP), and N-methyl nitrosourea (NMU)-induced ovarian and uterine toxicity and the role of Calliandra portoricensis in mitigating toxicity. In a bid to illuminate folk medical claims cloaked in mystery, unearthing lost knowledge, advance natural chemopreventive agents, and report new evidence lacking in the literature attributed to CP. Although CP is known to exhibit anticonvulsant, antidiarrheal, antipyretic, antirheumatic, and analgesic effects in humans, its possible roles for mitigating toxicity stemming from inadvertent chemical exposures are reported here. Our findings affirm and further show that CP abates toxic response incumbent on oxidative damage and inflammatory responses associated with NMU and BaP exposure. Development of phytochemical derived from CP may serve as a potential natural therapy against chemical toxicities in individuals inadvertently exposed, and promote human health and reproductive satiety.
Asunto(s)
Benzo(a)pireno/toxicidad , Fabaceae/química , Inflamación/patología , Metilnitrosourea/toxicidad , Ovario/patología , Útero/patología , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Femenino , Hormonas/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/enzimología , Oxidación-Reducción , Extractos Vegetales/farmacología , Ratas Sprague-Dawley , Útero/efectos de los fármacos , Útero/enzimología , Vincristina/farmacología , Proteína X Asociada a bcl-2/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Calliandra portoricensis (CP) is a herb widely used in Nigeria for the treatment of breast engorgement. However, the scientific evidence of this use and its mechanisms of action is not clearly understood. AIM OF THE STUDY: We assessed the chemopreventive effects of methanol extract of CP on N-methyl-N-nitrosourea (NMU)-induced mammary gland toxicity in rats. MATERIALS AND METHODS: Fingerprinting of methanol extract of CP by Gas Chromatography-Mass Spectrometry (GC-MS) was done. Female Wistar rats were assigned into eight groups: Group 1 (control), group 2 received NMU only, groups 3, 4 and 5 received NMU and treated with CP at doses of 100, 200 and 300â¯mg/kg, respectively. Group 6 received CP (300â¯mg/kg), group 7 received NMU and vincristine, while group 8 received vincristine. RESULTS: The weight-gain by rats decreased in all groups that received NMU. Administration of NMU significantly increased organo-somatic weight of mammary gland by 52%. The NMU increased serum nitric oxide, total bilirubin, mammary myeloperoxidase and lipid peroxidation by 76%, 87%, 130% and 21%, respectively, as well as activities of serum aspartate aminotransferase and lactate dehydrogenase. Also, NMU-treated rats had decreased total sulphydryl, reduced glutathione and catalase. Immunohistochemistry revealed strong expression of estrogen, progesterone and EGFR-2 proteins in NMU-treated rats. Treatment with CP (200 and 300â¯mg/kg) attenuated NMU-induced inflammation and oxidative stress. CONCLUSION: CP ameliorated NMU-induced toxicity by modulating different cellular targets.
Asunto(s)
Anticarcinógenos/uso terapéutico , Fabaceae , Neoplasias Mamarias Experimentales/prevención & control , Extractos Vegetales/uso terapéutico , Animales , Anticarcinógenos/farmacología , Carcinógenos , Catalasa/metabolismo , Quimioprevención , Femenino , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Metilnitrosourea , Extractos Vegetales/farmacología , Raíces de Plantas , Ratas Wistar , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: Annona muricata is used in traditional African medicine to manage urinary obstruction. In this study, we hypothesized that hexane fraction of Annona muricata (HFAM) seeds will ameliorate testosterone propionate (Tp)-induced benign prostatic hyperplasia (BPh). METHODS: Castrated rats were assigned into six groups: non-castrated control, castrated control, castrated rats that received Tp (BPh group), [BPh+HFAM], [BPh+HFAM + finasteride], [BPh + finasteride]. RESULTS: The BPh rats had 3.8 and 3.9 folds increases in prostatic and organo-somatic weight, while treatment with HFAM alone and [HFAM + finasteride] decreased prostatic weight by 22% and 34%, respectively. BPh increased the activities of serum and prostatic total acid phosphatase by 95% and 121%; and activities of serum and prostatic alkaline phosphatase by 54% and 281%, respectively. Serum and prostatic lipid peroxidation were increased by 44% and 82%, respectively, in BPh rats with a concomitant decrease in prostatic superoxide dismutase by 73%. In BPh rats, serum and prostatic myeloperoxidase increased by 4.0 and 2.0 folds, while serum nitric oxide increased by 2.4 folds, respectively. Strong expression of inducible nitric oxide synthase, Bcl2, beta-catenin, androgen and estrogen receptors were observed in BPh rats. Importantly, treatment with HFAM or finasteride (or combination) attenuated prostatic weight, inflammatory and antioxidant indices in BPh rats. CONCLUSION: HFAM may serve as novel therapeutic agent against BPh.
Asunto(s)
Annona , Extractos Vegetales/uso terapéutico , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológico , Semillas , Testosterona/toxicidad , Animales , Hexanos/aislamiento & purificación , Hexanos/uso terapéutico , Masculino , Extractos Vegetales/aislamiento & purificación , Hiperplasia Prostática/patología , Ratas , Ratas WistarRESUMEN
A biorefinery process for high yield production of succinic acid from biomass sugars was investigated using recombinant Escherichia coli. The major problem been addressed is utilization of waste biomass for the production of succinic acid using metabolic engineering strategy. Here, methanol extract of Strophanthus preussii was used for fermentation. The process parameters were optimized. Glucose (9 g/L), galactose (4 g/L), xylose (6 g/L) and arabinose (0.5 g/L) were the major sugars present in the methanol extract of S. preussii. E. coli K3OS with overexpression of soluble nucleotide pyridine transhydrogenase sthA and mutation of lactate dehydrogenase A (ldhA), phosphotransacetylase acetate kinase A (pta-ackA), pyruvate formate lyase B (pflB), pyruvate oxidase B (poxB), produced a final succinic acid concentration of 14.40 g/L and yield of 1.10 mol/mol total sugars after 72 h dual-phase fermentation in M9 medium. Here, we show that the maximum theoretical yield using methanol extracts of S. preussii was 64%. Hence, methanol extract of S. preussii could be used for the production of biochemicals such as succinate, malate and pyruvate.
Asunto(s)
Apocynaceae/química , Escherichia coli , Metanol/química , Microorganismos Modificados Genéticamente , Extractos Vegetales , Ácido Succínico/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Microorganismos Modificados Genéticamente/genética , Microorganismos Modificados Genéticamente/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. METHODS: BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. RESULTS: The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. CONCLUSION: MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.
Asunto(s)
Acetatos/uso terapéutico , Apoptosis , Ciclopentanos/uso terapéutico , Inflamación/patología , Oxilipinas/uso terapéutico , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológico , Testosterona/efectos adversos , Acetatos/farmacología , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/sangre , Ciclopentanos/farmacología , Finasterida/farmacología , Finasterida/uso terapéutico , Inflamación/complicaciones , Lípidos/sangre , Masculino , Fase I de la Desintoxicación Metabólica , Óxido Nítrico/sangre , Tamaño de los Órganos/efectos de los fármacos , Oxilipinas/farmacología , Próstata/efectos de los fármacos , Próstata/patología , Hiperplasia Prostática/sangre , Hiperplasia Prostática/enzimología , Ratas Wistar , Testosterona/administración & dosificación , Testosterona/sangre , Aumento de Peso/efectos de los fármacosRESUMEN
Prostate cancer (PCa) is an international health problem and search for its effective treatment is in progress. Punicalagin (PN), polyphenol from pomegranate fruit, is known to exhibit potent anticancer activity in lung, breast and cervical cells. However, there is paucity of information on its effect in PCa. This study evaluated anti-proliferative effects of PN and its effects on extrinsic pathway of apoptosis in PCa cells, and angiogenesis in chicken chorioallantoic membrane (CAM). Antioxidant activities of PN were determined by 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging and inhibition of lipid peroxidation (LPO) methods. PCa (PC-3 and LNCaP) and normal prostate (BPH-1) cells were cultured and treated with PN (10, 50 and 100 µM). Cytotoxicity and viability effects of PN were determined by lactate dehydrogenase (LDH) and XTT assays, respectively. Antiangiogenic effects were measured using CAM assay, while apoptosis was assessed by DNA fragmentation, enrichment factor by Cell Death Detection ELISA kit and expressions of caspases-3 and -8. Results showed that PN (10-200 µM) significantly scavenged DPPH and inhibited LPO in a concentration-dependent manner. Furthermore, PN (10-100 µM) concentration-dependently inhibited viability in PC-3 and LNCaP, while viability in BPH-1 was insignificantly affected. PN had low toxicity on cells in vitro at concentrations tested. Also, PN (100 µM) increased enrichment factor in PC-3 (2.34 ± 0.05) and LNCaP (2.31 ± 0.26) relative to control (1.00 ± 0.00). In addition, PN (50 µM) decreased the network of vessels in CAM, suggesting its anti-angiogenic effect. Moreso, PN increased the expressions of caspases-3 and -8 in PC-3. Overall, PN exerts anti-proliferative activity in PCa cells via induction of apoptosis and anti-angiogenic effect.
Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Taninos Hidrolizables/farmacología , Lythraceae/química , Extractos Vegetales/química , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Caspasa 3/análisis , Caspasa 8/análisis , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Frutas/química , Frutas/metabolismo , Humanos , Taninos Hidrolizables/química , Taninos Hidrolizables/aislamiento & purificación , Peroxidación de Lípido/efectos de los fármacos , Lythraceae/metabolismo , Masculino , Neovascularización Fisiológica/efectos de los fármacos , Polifenoles/química , Ratas , Ratas WistarRESUMEN
BACKGROUND: Our previous studies showed that fruit methanol extract from Xylopia aethiopica (MEXA) exhibited antiproliferative activity in human cervical cancer cells via the induction of apoptosis. The present study was designed to assess the antiproliferative, antiangiogenic and antioxidant effects of MEXA on prostate cancer (PCa) cells (PC-3 and LNCaP). METHODS: PC-3 and LNCaP cells were cultured and treated with MEXA (10, 50 and 100 µg/mL). The sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) and lactate dehydrogenase (LDH) assays were used to evaluate cell viability and cytotoxicity, respectively. DNA fragmentation was determined by cell death detection ELISA plus, and angiogenesis was assessed by chicken chorioallantoic membrane (CAM) assay. The antioxidant activities of MEXA were determined by DPPH and hydroxyl (OH) radicals' scavenging methods as well as through the inhibition of lipid peroxidation (LPO) in rats' liver homogenate. RESULTS: MEXA at 100, 250 and 500 µg/mL scavenged DPPH by 48%, 62%, 70% and OH radical by 39%, 58%, 67%, respectively. MEXA significantly (p<0.05) inhibited LPO in a concentration-dependent manner. In addition, MEXA had antiproliferative effects on PC-3 and LNCaP with IC50 of 62.1 and 73.6 µg/mL, respectively, at 96 h. The LDH assay showed that MEXA had low toxicity in vitro at its IC50 values. The extent of DNA fragmentation by MEXA showed higher values in PC-3 and LNCaP, suggesting the possible induction of apoptosis. In contrast, MEXA did not affect the network of vessels in CAM, thus lacking anti-angiogenic property. CONCLUSIONS: These findings suggest that MEXA induces antiproliferative activity in PCa cells through a mechanism that involves apoptosis. Therefore, MEXA may be a potential therapeutic agent for PCa.
Asunto(s)
Antioxidantes/farmacología , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Xylopia/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Frutas/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Metanol/química , Ratas , Ratas WistarRESUMEN
Benign prostate hyperplasia (BPH) is a progressive disease that is related to age. Known therapeutic agents used in the treatment of BPH are associated with toxicity. Therefore, chemoprevention could be an effective approach. We investigated the ameliorative effects of methyl jasmonate (MeJA) in testosterone propionate (TP)-induced BPH in castrated rats. Castration was performed by removing both testes through the scrotum sack under ketamine anesthesia. Rats were assigned into seven groups of seven animals each: non-castrated control, castrated control, castrated rats that received TP, castrated rats that received TP and MeJA, castrated rats that received TP and finasteride, castrated rats that received MeJA, and castrated rats that received finasteride. Results indicate that BPH rats had significantly (p < 0.05) elevated prostate weight and relative weight of prostate relative to control. Also, BPH rats had significantly (p < 0.05) increased activities of prostatic acid and alkaline phosphatases, levels of zinc, and malondialdehyde. Further, levels of enzymic and non-enzymic antioxidative indices were significantly (p < 0.05) reduced in BPH. Histology of prostate revealed hyperplasia of transition lobe, increased expression of PSA, and Ki67 in BPH. Treatment with MeJA and finasteride attenuated the activities of the phosphatases and levels of antioxidants in BPH. Overall, MeJA ameliorates BPH via antioxidative mechanism. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Acetatos/química , Ciclopentanos/química , Oxilipinas/química , Extractos Vegetales/química , Hiperplasia Prostática/tratamiento farmacológico , Propionato de Testosterona/química , Testosterona/química , Animales , Humanos , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Nymphaea lotus (NL) is an aquatic perennial plant used traditionally in the management of various liver diseases. In this study, the protective effect of methanol extract of NL against carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats was investigated. METHODS: Male Wistar rats were assigned into six groups of five rats each. Group I received corn oil (0.5 mL p.o.) and served as control, group II received CCl4 (1 mL/kg i.p., 1:3 in corn oil), group III received NL (200 mg/kg), and groups IV, V, and VI received CCl4+NL (50, 100, and 200 mg/kg, respectively) for 6 weeks. Twenty-four hours after the last exposure, rats were bled and killed. RESULTS: The activities of alanine aminotransaminase (ALT), aspartate aminotransferase (AST), and levels of total bilirubin (TB) in the serum, thiobarbituric acid reactive substances (TBARS), superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione (GSH) in the liver, and histopathology of the liver were determined using standard procedures. NL significantly (p<0.05) lowered the levels of ALT, AST, and TB and exhibited antioxidant potentials in rats exposed to CCl4 relative to the control values. Specifically, NL at 100 and 200 mg/kg significantly (p<0.05) increased CCl4-induced decrease in hepatic GSH and GPx and also decreased the level of hepatic TBARS in CCl4-intoxicated rats. Histopathological findings revealed cellular infiltration and fibrosis in rats that received CCl4 only, which were ameliorated in rats that received NL+CCl4. CONCLUSIONS: The data suggest that NL exhibited hepatoprotective effects in CCl4-intoxicated rats via antioxidative mechanism.
Asunto(s)
Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Metanol/uso terapéutico , Nymphaea , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Masculino , Metanol/farmacología , Estrés Oxidativo/fisiología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas WistarRESUMEN
Background: Medicinal plants have been used as therapeutic agents since prehistoric era. Artocarpus altilis (Breadfruit)is used in African traditional medicine to treat hypertension with scanty information on its safety profile in animals.Objectives: This study was designed to evaluate the toxicological effects of oral administration of methanol extract of Artocarpus altilis (MEAA) in rats.Materials and Methods: Thirty male Wistar rats were divided into 6 groups of 5 animals each and were treated orally with corn oil (control), 100, 250, 500, 1000 and 2000 mg/kg of MEAA for twenty one days.Results: MEAA caused insignificant (p>0.05) changes in the activities of serum alanine and aspartate aminotransferases(ALT and AST) and alkaline phosphatase (ALP) relative to the control. Cardiac and hepatic AST (114.8±4.8 and(111.0±1.0) serum urea (1.1±0.2), creatinine (0.3±0.1), lactate dehydrogenase (17.3±5.8) and creatinine kinase (15.5±4.4)were significantly decreased (p<0.05) in rats treated with 2000 mg/kg of MEAA when compared to control [(134.8±5.8and 129.7±5.0), 2.94±0.3, 0.4±0.1, 38.5±13.3 and 41.3±2.9]. The MEAA significantly decreased (p<0.05) serum total cholesterol and triglyceride while high density lipoprotein- cholesterol (HDL-c) level was increased. Histopathological examination of liver, kidney and aorta slides from MEAA- treated rats showed little alteration from the control.Conclusions: The MEAA could be safe when used over a long period for therapeutic purposes
Asunto(s)
Artocarpus , Fenómenos Bioquímicos , Metanol , Nigeria , Plantas Medicinales , Ratas WistarRESUMEN
BACKGROUND: Tuberculosis (TB) is a global health problem. The effects of anti-TB drugs on male reproductive system have not been properly evaluated. We investigated the effects of anti-TB drugs on testicular antioxidant indices, sperm characteristics and hormonal levels in rats, and the protective role of kolaviron (KV), a biflavonoid from Garcinia kola seed. METHODS: Twenty-eight male Wistar rats were assigned into four groups and orally treated with corn oil (control), anti-TB drugs [4-Tabs=isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (15 mg/kg) and ethambutol (15 mg/kg) in combination], anti-TB drugs +KV and KV alone (200 mg/kg). Anti-TB drugs and KV were given three times per week for 8 weeks. In vitro, reducing power, inhibition of lipid peroxidation (LPO), diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging effects of KV were examined. RESULTS: KV at 10, 20, 50 and 100 µg/mL showed strong reducing potential and effectively scavenged DPPH and OH radicals in a concentration-dependent manner. Furthermore, KV significantly inhibited LPO in rats' liver homogenate. In vivo, administration of 4-Tabs caused a significant (p<0.05) decrease in body weight gain and weight of testis of rats. Body weight gain and weight of testis decreased by 45% and 36%, respectively, in the 4-Tabs-treated rats. Also, 4-Tabs increased testicular lipid peroxidation by 82%, with a concomitant decrease in antioxidant indices. Testicular reduced glutathione, superoxide dismutase and glutathione peroxidase decreased by 2.2-, 1.9- and 1.6-folds, respectively. Likewise, 4-Tabs markedly decreased sperm count, motility, luteinizing hormone and testosterone. Co-administration of KV with 4-Tabs normalized body weight, enhanced antioxidant system and improved sperm characteristics. CONCLUSIONS: Kolaviron protects male reproductive system from oxidative damage by anti-tuberculosis drugs via the antioxidative mechanism.
Asunto(s)
Antituberculosos/farmacología , Biflavonoides/farmacología , Garcinia kola/química , Hormonas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Semillas/química , Animales , Antioxidantes/metabolismo , Compuestos de Bifenilo/farmacología , Flavonoides/farmacología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Picratos/farmacología , Ratas , Ratas Wistar , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismoRESUMEN
OBJECTIVE: Prostate cancer (PCa) is a major health concern. Calliandra portoricensis (CP) is traditionally known for its analgesic, anti-ulcerogenic and anticonvulsant properties. However, its antiproliferative properties for PCa still need to be investigated. METHODS: Antioxidant activities of CP were determined by 1,1-diphenyl-2-picryhydrazyl (DPPH) and hydroxyl (OH(-)) radicals-scavenging methods. PC-3 and LNCaP (androgen-refractory and androgen-dependent PCa-derived cell lines) were cultured and treated with CP (10, 50 and 100 µg/mL). Effects of CP on cells were determined by cytotoxicity assay (lactate dehydrogenase, LDH) and viability assay (sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate, XTT). DNA fragmentation was detected by cell death detection enzyme-linked immunosorbent assay plus kit. CP was tested as an inhibitor of angiogenesis using chicken chorioallantoic membrane (CAM) assay. RESULTS: CP showed significant scavenging of DPPH and OH(-) radicals. CP significantly (P<0.05) inhibited lipid peroxidation in a dose-dependent manner. Precisely, CP (10, 50 and 100 µg/mL) inhibited PC-3 and LNCaP growth by 7%, 74% and 92%, and 27%, 73%, and 85% respectively at 48 h. CP had low toxicity in vitro at its half inhibitory concentration dose. Detection of cell death induced by CP at 50 µg/mL showed higher enrichment factors in LNCaP (7.38±0.95) than PC-3 (3.48±0.55). Also, treatment with CP (50 µg/mL) significantly reduced network of vessels in CAM, suggesting its antiangiogenic potential. CONCLUSION: Calliandra portoricensis elicited antioxidant, antiangiogenic and antiproliferative effects in PCa cells.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Fabaceae , Extractos Vegetales/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Humanos , Masculino , Raíces de Plantas , Neoplasias de la Próstata/patología , Ratas , Ratas WistarRESUMEN
OBJECTIVE@#To investigate the antimalarial potential of kolaviron (KV), a biflavonoid fraction from Garcinia kola seeds, against Plasmodium berghei (P. berghei) infection in Swiss albino mice.@*METHODS@#The study consists of seven groups of ten mice each. Groups I, II and III were normal mice that received corn oil, KV1 and chloroquine (CQ), respectively. Groups IV, V, VI and VII were infected mice that received corn oil, CQ, KV1 and KV2, respectively. CQ, KV1 and KV2 were given at 10-, 100- and 200-mg/kg daily, respectively for three consecutive days.@*RESULTS@#Administration of KV1 and KV2 significantly (P<0.05) suppressed P. berghei-infection in the mice by 85% and 90%, respectively, while CQ produced 87% suppression relative to untreated infected group after the fifth day of treatment. Also, KV2 significantly (P<0.05) increased the mean survival time of the infected mice by 175%. The biflavonoid prevented a drastic reduction in PCV from day 4 of treatment, indicating its efficacy in ameliorating anaemia. Significant (P<0.05) oxidative stress assessed by the elevation of serum and hepatic malondialdehydewere observed in untreated P. berghei-infected mice. Specifically, serum and hepatic malondialdehyde levels increased by 93% and 78%, respectively in the untreated infected mice. Furthermore, antioxidant indices, viz; superoxide dismutase, catalase, glutathione-s-transferase, gluathione peroxidase and reduced gluathione decreased significantly (P<0.05) in the tissues of untreated P. berghei-infected mice. KV significantly (P<0.05) ameliorated the P. berghei-induced decrease in antioxidant status of the infected mice.@*CONCLUSIONS@#This study shows that kolaviron, especially at 200 mg/kg, has high antimalarial activities in P. berghei-infected mice, in addition to its known antioxidant properties.
Asunto(s)
Animales , Masculino , Ratones , Análisis de Varianza , Antimaláricos , Farmacología , Antioxidantes , Peso Corporal , Cloroquina , Farmacología , Flavonoides , Farmacología , Garcinia kola , Química , Hígado , Química , Malaria , Quimioterapia , Oxidorreductasas , Sangre , Parasitemia , Quimioterapia , Extractos Vegetales , Farmacología , Plasmodium berghei , Semillas , QuímicaRESUMEN
In previous studies, we established that kolaviron (KV) (a biflavonoid from Garcinia kola seeds) elicited anti-oxidative and hepatoprotective effects in Wistar rats chronically treated with ethanol. The present study investigates the possible ameliorative effect of KV against ethanol-induced reproductive toxicity in male Wistar rats. Twenty-eight rats were randomly divided into four groups of seven animals each; Group 1 (control) was administered corn oil, group 2 was given 45%v/v ethanol at 3g/kg body weight, group 3 received ethanol and KV (200mg/kg) simultaneously and group 4 received KV alone. All drugs were given daily by oral gavage for 21 consecutive days. Ethanol treatment resulted in a significant (p<0.05) decrease in relative weight of testis of the animals. In the spermatozoa, ethanol intoxication resulted in 54%, 21% and 38% decreases in testicular protein content, sperm motility and count, respectively. In addition, ethanol administration enhanced lipid peroxidation (LPO) process assessed by the accumulation of malondialdehyde (MDA) in the testis. Precisely, MDA level was increased by 121% in the testis of ethanol-treated rats relative to the control. Furthermore, levels of testicular glutathione and activities of testicular antioxidant enzymes such as superoxide dismutase and catalase were significantly (p<0.05) reduced in ethanol-treated rats. Histopathology showed extensive degenerative changes in seminiferous tubules and defoliation of spermatocytes in testis of ethanol-treated rats. Interestingly, co-administration of KV with ethanol led to almost complete inhibition of testicular LPO thereby enhancing antioxidant status of the testis. Overall, KV ameliorates ethanol-induced toxic assault on testis and improves seminal qualities of the rats.
Asunto(s)
Biflavonoides , Garcinia kola , Animales , Etanol/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Semillas , Espermatozoides/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacosRESUMEN
BACKGROUND: Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infections and has been reported to be toxic to the male reproductive system. This study was designed to evaluate the ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola, on NVP-induced testicular toxicity. METHODS: The adult male Wistar rats were given two and four times therapeutic doses of NVP (NVP-2T and NVP-4T; 18 and 36 mg/kg NVP) alone or in combination with KV (200 mg/kg). NVP was given daily, whereas KV was administered five times in a week by oral gavage. RESULTS: Treatment with NVP did not alter the body weight gain and relative weight of testis of the rats. NVP-4T significantly (p<0.05) decreased the sperm motility, protein content, and live-dead ratio and also increased the percentage sperm abnormalities of the rats. Although NVP-4T significantly increased sperm abnormalities, it has no effect on epididymal sperm count. Also, NVP-4T caused a significant (p<0.05) elevation of serum aminotransferases and γ-glutamyl transferase activities. In addition, NVP-4T significantly (p<0.05) decreased the levels of testicular superoxide dismutase, catalase, glutathione S-transferase, and glutathione with marked elevation of malondialdehyde (index of lipid peroxidation) in the rats. In contrast, NVP-2T did not produce an adverse effect on the biochemical indices studied in testes and sperm of rats. Supplementation with KV significantly ameliorated the biochemical changes caused by NVP-4T. CONCLUSIONS: Taken together, KV reversed the adverse effects of NVP-4T on testicular antioxidant enzymes and markers of oxidative stress in the rats.
Asunto(s)
Flavonoides/farmacología , Garcinia kola/química , Nevirapina/toxicidad , Extractos Vegetales/farmacología , Inhibidores de la Transcriptasa Inversa/toxicidad , Testículo/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/aislamiento & purificación , Masculino , Estructura Molecular , Nevirapina/química , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Wistar , Inhibidores de la Transcriptasa Inversa/química , Semillas/química , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Testículo/enzimología , Testículo/metabolismo , Testículo/patologíaRESUMEN
BACKGROUND: Tenofovir (TFR) is a nucleotide reverse transcriptase inhibitor with activity against human immunodeficiency virus. We studied the effect of TFR administered to Wistar rats on hepatic and renal function markers and the possible modulatory role of vitamin E (Vit E). METHODS: The study consists of four groups of six rats each. The first group served as control, the second group received TFR at 50 mg/kg/day for 4 weeks, third group received TFR and Vit E, and the last group received Vit E alone. RESULTS: TFR administration caused a significant (p<0.05) increase in the levels of serum urea, creatinine, urinary glucose, and protein by 65%, 51%, 88%, and 79%, respectively, relative to controls. This was followed by a significant (p<0.05) reduction in creatinine clearance of TFR-treated rats. There were no significant differences (p>0.05) in the activities of serum aminotransferases, γ-glutamyltransferase, and alkaline phosphatase in TRF-treated rats relative to controls. TFR administration caused a marked elevation of malondialdehyde (MDA; index of lipid peroxidation) in the animals. Specifically, serum, hepatic, and renal MDA levels increased by 75%, 90%, and 102%, respectively. TRF-treated rats had significantly (p<0.05) reduced activities of renal catalase, glutathione-S-transferase, and superoxide dismutase. Supplementation of Vit E ameliorated TFR-induced effects by decreasing the levels of MDA and enhancing the activities of renal antioxidative enzymes. The biochemical data were supported by histopathological findings from the slides. CONCLUSIONS: TFR increased oxidative stress and altered kidney function markers in the rats, whereas supplementation of Vit E attenuated these effects.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/toxicidad , Organofosfonatos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Vitamina E/farmacología , Adenina/toxicidad , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Pruebas de Función Renal , Hígado/efectos de los fármacos , Hígado/metabolismo , Pruebas de Función Hepática , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , TenofovirRESUMEN
BACKGROUND: Kolaviron (KV) (biflavonoid from Garcinia kola) and extract of Curcuma longa (CL) are frequently used in folk medicine for treatment of hypertension. One of their mechanisms of action is to enhance antioxidant properties in animals. N(G)- nitro- l- arginine methyl- ester (L- NAME) is L- arginine analogue, which by binding to Nitric Oxide Synthase (NOS) may induce hypertension partly due to increase in tissues oxidative stress. OBJECTIVES: To investigate the effect of L- NAME on some biochemical indices and the possible protective effect of KV or CL. MATERIALS AND METHODS: Four groups consisting of 6 rats each were used. One group served as control, second group received L- NAME (40 mg/kg/day). Third and fourth groups were treated with KV and CL, respectively and also received L- NAME. KV and CL were given at a dose of 200 mg/kg/day. RESULTS: L- NAME caused a significant (P <0.05) increase in the levels of serum urea, creatine kinase and alanine aminotransferase relative to controls. L- NAME treated rats had markedly decreased hepatic catalase (CAT), superoxide dismutase (SOD), glutathione- S- transferase (GST) and reduced glutathione (GSH) levels. Precisely, L- NAME decreased CAT, SOD, GST and GSH by 48, 52, 76 and 40%, respectively. L- NAME intoxication significantly decreased (P <0.05) renal GSH and SOD levels. Also, L- NAME caused a significant (P <0.05) induction of lipid peroxidation (LPO) in the animals. Administration of KV or CL with L- NAME caused significant (P <0.05) inhibition of LPO and augments tissue antioxidant indices. CONCLUSION: These results confirm the adverse effect of L- NAME on biochemical indices and, the ability of kolaviron or Curcuma longa to ameliorate the alterations.
RESUMEN
OBJECTIVE: To justify the use of African mistletoe (AM) Viscum album (V. album) in folkoric medicine to treat diabetes. METHODS: In one experiment, the fasting blood glucose (FBG) levels of diabetic rats were monitored for 4 h. Diabetic rats were treated with AM at doses of 50 mg/kg (AM1) and 100 mg/kg (AM2), glibenclamide (GB) (positive control) and saline solution (SS). In another experiment, diabetic rats were treated with AM2, GB and SS daily for 3 weeks. RESULTS: AM1 and AM2 elicited significant (P<0.05) hypoglycaemic effects within 4 h of extract administration. AM1 and AM2 decreased the FBG by 41% and 49%, respectively, at 2 h. AM2 was found to lower FBG by 51%, relative to baseline, which was comparable to GB at 3 h. In the second experiment, AM2 and GB significantly (P<0.05) decreased the FBG by 34% and 51%, respectively. This was followed by marked decrease in levels of HbA1C in AM2- and GB- treated diabetic rats. AM2 significantly (P<0.05) decreased the STZ-induced increase in levels of serum triglyceride, urea, lactate dehydrogenase, α-amylase and low-density lipoprotein-cholesterol. Furthermore, diabetic rats treated with AM2 had significantly (P<0.05) elevated high-density lipoprotein-cholesterol. In contrast, STZ administration produced insignificant (P<0.05) effect on the levels of serum creatinine and total bilirubin. CONCLUSIONS: Extract of African mistletoe has anti-diabetic and anti-hyperlipidemic effects in STZ-diabetic rats. AM may find clinical application in the amelioration of diabetes-induced lipid disorders.