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Antioxidant-rich supplementation plays an essential role in the function of mammals' central nervous system. However, no research has documented the effect of berberine (BER) supplementation on the cerebrocerebellar function of prepubertal rats. The present study was designed to investigate the impact of BER supplementation on neurochemical and behavioural changes in prepubertal male rats. Five groups (90 ± 5 g, n = 7 each) of experimental rats were orally treated with corn oil or different doses of BER (25, 50, 100, and 200 mg/kg bw) from the 28th at 68 post-natal days. On the 69 days of life, animals underwent behavioural assessment in the open field, hanging wire, and negative geotaxis tests. The result revealed that BER administration improved locomotive and motor behaviour by increasing distance travelled, line crossings, average speed, time mobile, and absolute turn angle in open field test and decrease in time to re-orient on an incline plane, a decrease in immobility time relative to the untreated control. Furthermore, BER supplementation increased (p < 0.05) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (p < 0.05) in oxidative and inflammatory levels as indicated by decreases in RONS, LPO, XO, carbonyl protein, NO, MPO, and TNF-α compared to the untreated control. BER-treated animals a lessened number of dark-stained Nissl cells compared to the untreated control rats. Our findings revealed that BER minimised neuronal degeneration and lesions, improved animal behaviour, and suppressed oxidative and inflammatory mediators, which may probably occur through its agonistic effect on PPAR-α, PPAR-δ, and PPAR-γ - essential proteins known to resolve inflammation and modulate redox signalling towards antioxidant function.
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Antioxidantes , Berberina , Ratas Wistar , Animales , Masculino , Ratas , Berberina/farmacología , Berberina/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/metabolismo , Cerebelo/metabolismo , Cerebelo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Glutatión/metabolismo , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismoRESUMEN
Sodium fluoride (NaF) ingestion has several detrimental effects in humans and rodents. NaF mechanisms of toxicity include perturbation of intracellular redox homeostasis and apoptosis. Betaine (BET) is a modified amino acid with anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigates BET's effect on NaF-induced hepatorenal toxicities in rats. Experimental rats (n = 30) were randomly assigned to groups (n = 6) and treated by gavage for 28 days. Group I (2 mL of distilled water), Group II (NaF: 9 mg/kg) alone, Group III: (BET: 100 mg/kg), Group IV: (NaF: 9 mg/kg and BET 1: 50 mg/kg), and Group V: (NaF: 9 mg/kg and BET 2: 100 mg/kg). Our findings revealed significantly (p < 0.05) increased hepatic transaminase activities alongside creatinine and urea levels following NaF-alone treatment in addition to increased oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, decreased superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, glutathione, and total sulfhydryl groups. The reduced levels of nuclear factor erythroid 2-related factor-2 and the activities of heme oxygenase-1, thioredoxin, and thioredoxin reductase in NaF-alone treated rats equally compromised cellular molecular responses to oxidative stress. Also, NaF increased (p < 0.05) hepatorenal inflammatory biomarkers-nitric oxide, interleukin-10, myeloperoxidase, and xanthine oxidase. Furthermore, caspase-3 and caspase-9 were increased (p < 0.05) in rats treated with NaF alone. Contrastingly, BET was observed to alleviate the harmful effects of NaF. Treatment with BET mitigated NaF-induced oxido-inflammatory responses and apoptosis in the experimental rat's hepatorenal system. The study demonstrates the potential of BET to abate NaF-induced hepatorenal toxicity.
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Epirubicin (EPI) is an effective chemotherapeutic against breast cancer, though EPI-related cardiotoxicity limits its usage. Endogenously derived 3-indolepropionic acid (3-IPA) from tryptophan metabolism is of interest due to its antioxidant capabilities which may have cardioprotective effects. Supplementation with 3-IPA may abate EPI's cardiotoxicity, and herein we studied the possibility of lessening EPI-induced cardiotoxicity in Wistar rats. Experimental rats (n = 30; BW 180-200 g) were randomly distributed in five cohorts (A-E; n = 6 each). Group A (control), Group B (EPI 2.5 mg/mL), and group C (3-IPA 40 mg/kg) while Groups D and E were co-treated with EPI (2.5 mg/mL) together with 3-IPA (D: 20 and E: 40 mg/kg). Following sacrifice, oxidative status, lipid profile, transaminases relevant to cardiac function, and inflammatory biomarkers were analysed. Also, 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and cardiac troponin T (cTnT) levels were assessed using an enzyme-linked immunosorbent assay (ELISA). EPI-initiated increases in cardiotoxicity biomarkers were significantly (p < 0.05) reduced by 3-IPA supplementation. Decreased antioxidant and increases in reactive oxygen and nitrogen species (RONS), 8-OHdG and lipid peroxidation were lessened (p < 0.05) in rat hearts co-treated with 3-IPA. EPI-induced increases in nitric oxide and myeloperoxidase were reduced (p < 0.05) by 3-IPA co-treatment. In addition, 3-IPA reversed EPI-mediated alterations in alanine aminotransferase (ALT), aspartate amino transaminases (AST), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and serum lipid profile including total cholesterol and triglycerides. Microscopic examination of the cardiac tissues showed that histopathological lesions severity induced by EPI was lesser in 3-IPA co-treated rats. Our findings demonstrate that supplementing endogenously derived 3-IPA can enhance antioxidant protection in the cardiac tissue susceptible to EPI toxicity in female rats. These findings may benefit breast cancer patients undergoing chemotherapy by further validating these experimental data.
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Neoplasias de la Mama , Cardiotoxicidad , Humanos , Ratas , Femenino , Animales , Epirrubicina/toxicidad , Epirrubicina/metabolismo , Cardiotoxicidad/tratamiento farmacológico , Miocitos Cardíacos/metabolismo , Ratas Wistar , Antioxidantes/uso terapéutico , Troponina T , Propionatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama/metabolismo , Biomarcadores/metabolismo , Estrés OxidativoRESUMEN
We investigated the impact of Coartem™ (COA) and aflatoxin B1 (AFB1) on rats' hypothalamus, epididymis, and testis. Male rats were randomly grouped (n = 5 rats) and treated: control group (corn oil), AFB1 (70 µg/kg), COA (5 mg/kg), COA + AFB1 (5 + 0.035 mg/kg) and COA + AFB1 (5 + 0.07 mg/kg) for 28 days. Blood samples were collected for serum prolactin, testosterone, follicle-stimulating and luteinising hormones (FSH and LH) assay upon sacrifice. The semen, hypothalamus, epididymis, and testes were harvested for morphological, biochemical, and histopathology determination of oxidative, inflammation stress, genomic integrity, and pathological alterations. Exposure to the COA and AFB1 caused the cauda epididymal spermatozoa to display low motility, viability, and volume, with increased abnormalities. Hormonal disruption ensued in animals exposed to COA and AFB1 alone or together, exemplified by increased prolactin, and decreased testosterone, FSH and LH levels. Treatment-related reduction in biomarkers of testicular metabolism-acid and alkaline phosphatases, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase-were observed. Also, COA and AFB1 treatment caused reductions in antioxidant (Glutathione and total thiols) levels and antioxidant enzyme (Catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase) activities in the examined organs. At the same time, treatment-related increases in DNA damage (p53), oxidative stress (xanthine oxidase, reactive oxygen and nitrogen species and lipid peroxidation), inflammation (nitric oxide and tumour necrosis factor-alpha), and apoptosis (caspase-9, and -3) were observed. Chronic exposure to COA and AFB1 led to oxidative stress, inflammation, and DNA damage in male rats' hypothalamic-reproductive axis, which might potentiate infertility if not contained.
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Antimaláricos , Antioxidantes , Ratas , Masculino , Animales , Antioxidantes/metabolismo , Antimaláricos/farmacología , Aflatoxina B1/metabolismo , Artesunato/farmacología , Lumefantrina/farmacología , Prolactina/metabolismo , Testículo/metabolismo , Estrés Oxidativo , Glutatión/metabolismo , Testosterona , Hormona Folículo Estimulante , Inflamación/metabolismoRESUMEN
The burden of infertility distresses millions of families worldwide. The harmful effects of aflatoxin B1 (AFB1) on the reproductive system involve oxidative stress, culminating in inflammation and cellular apoptosis. The phytochemical in Sorghum bicolor is rich in antioxidants and anti-inflammatory activities. The effect of Sorghum bicolor (L.) Moench (SBE-HP) extract -hydrophobic fraction- enriched in Apigenin (API) was investigated in rats chronically dosed with AFB1 and the likely mechanism (s) of SBE-HP to protect against AFB1-induced reproductive toxicity. Adult Wistar male rats (twenty-four) were selected randomly and allocated into four groups. Cohort 1 was administered 0.05 % carboxymethyl cellulose (CMC); cohort 2 received AFB1 (50 µg/kg) alone; while cohorts 3 and 4 received 5 & 10 mg/kg of (SBE-HP) respectively, along with 50 µg/kg of AFB1. After 28 days, AFB1 induced remarkable reproductive toxicity as evidenced by increased sperm abnormalities, lowered sperm quality and motility, altered serum hormonal levels and testicular enzyme activities, decreased anti-oxidants, increased pro-oxidants, apoptotic and inflammatory biomarkers, as well as altered histoarchitectural structure of the testis, epididymis, and hypothalamus of rats. API-enriched extract of S. bicolor reduced AFB1-induced oxidative, inflammatory, apoptotic, and histological derangement by improving sperm function parameters, testicular enzymes, and reproductive hormones. Anti-oxidant levels and anti-inflammatory mediators were increased while decreases in the activities and levels of pro-oxidants, pro-inflammatory molecules and caspase-9 occurred in the rats' testes, epididymis, and hypothalamus. API-enriched S. bicolor protected the testes, epididymis, and hypothalamus of male rats exposed to AFB1 by modulating oxidative stress, inflammation, and apoptosis.
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Aflatoxina B1 , Sorghum , Ratas , Masculino , Animales , Ratas Wistar , Aflatoxina B1/toxicidad , Sorghum/metabolismo , Especies Reactivas de Oxígeno , Semillas/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , Inflamación/inducido químicamente , Antiinflamatorios/uso terapéuticoRESUMEN
Aflatoxin B1 (AFB1) is a recalcitrant metabolite produced by fungi species, and due to its intoxications in animals and humans, it has been classified as a Group 1 carcinogen in humans. Preserving food products with Sorghum bicolor sheath can minimise the contamination of agricultural products and avert ill health occasioned by exposure to AFB1. The current study investigated the ameliorating effect of Sorghum bicolor sheath hydrophobic extract (SBE-HP) enriched in Apigenin (API) on the hepatorenal tissues of rats exposed to AFB1. The SBE-HP was characterised using TLC and LC-MS and was found to be enriched in Apigenin and its methylated analogues. The study used adult male rats divided into four experimental cohorts co-treated with AFB1 (50 µg/kg) and SBE-HP (5 and 10 mg/kg) for 28 days. Biochemical, enzyme-linked immunosorbent assays (ELISA) and histological staining were used to examine biomarkers of hepatorenal function, oxidative status, inflammation and apoptosis, and hepatorenal tissue histo-architectural alterations. Data were analysed using GraphPad Prism 8.3.0, an independent t-test, and a one-way analysis of variance. Co-treatment with SBE-HP ameliorated an upsurge in the biomarkers of hepatorenal functionality in the sera of rats, reduced the alterations in redox balance, resolved inflammation, inhibited apoptosis, and preserved the histological features of the liver and kidney of rats exposed to AFB1. SBE-HP-containing API is an excellent antioxidant regiment. It can amply prevent the induction of oxidative stress, inflammation, and apoptosis in the hepatorenal system of rats. Therefore, supplementing animal feeds and human foods with SBE-HP enriched in Apigenin may reduce the burden of AFB1 intoxication in developing countries with a shortage of effective antifungal agents.
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Aflatoxina B1 , Sorghum , Adulto , Ratas , Masculino , Humanos , Animales , Aflatoxina B1/toxicidad , Apigenina/farmacología , Apigenina/metabolismo , Hígado , Inflamación/metabolismo , Biomarcadores/metabolismoRESUMEN
Epirubicin's (EPI) efficacy as a chemotherapeutic agent against breast cancer is limited by EPI's neurotoxicity associated with increased oxidative and inflammatory stressors. 3-Indolepropionic acid (3-IPA) derived from in vivo metabolism of tryptophan is reported to possess antioxidative properties devoid of pro-oxidant activity. In this regard, we investigated the effect of 3-IPA on EPI-mediated neurotoxicity in forty female rats (180-200 g; five cohorts (n = 6) treated as follows: Untreated control; EPI alone (2.5 mg/Kg); 3-IPA alone (40 mg/Kg body weight); EPI (2.5 mg/Kg) + 3-IPA (20 mg/Kg) and EPI (2.5 mg/Kg) + 3-IPA (40 mg/Kg) for 28 days. Experimental rats were treated with EPI via intraperitoneal injection thrice weekly or co-treated with 3-IPA daily by gavage. Subsequently, the rat's locomotor activities were measured as endpoints of neurobehavioural status. After sacrifice, inflammation, oxidative stress and DNA damage biomarkers were assessed in rats' cerebrum and cerebellum alongside histopathology. Our results demonstrated that locomotor and exploratory deficits were pronounced in EPI-alone treated rats and improved in the presence of 3-IPA co-treatment. EPI-mediated decreases in tissue antioxidant status, increases in reactive oxygen and nitrogen species (RONS), as well as in lipid peroxidation (LPO) and xanthine oxidase (XO) were lessened in the cerebrum and cerebellum of 3-IPA co-treated rats. Increases in nitric oxide (NO) and 8-hydroxydeguanosin (8-OHdG) levels and myeloperoxidase MPO activity were also abated by 3-IPA. Light microscopic examination of the cerebrum and cerebellum revealed EPI-precipitated histopathological lesions were subsequently alleviated in rats co-treated with 3-IPA. Our findings demonstrate that supplementing endogenously derived 3-IPA from tryptophan metabolism enhances tissue antioxidant status, protects against EPI-mediated neuronal toxicity, and improves neurobehavioural and cognitive levels in experimental rats. These findings may benefit breast cancer patients undergoing Epirubicin chemotherapy.
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Antioxidantes , Neoplasias , Femenino , Ratas , Animales , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Epirrubicina/uso terapéutico , Epirrubicina/farmacología , Ratas Wistar , Triptófano/farmacología , Estrés Oxidativo , Especies Reactivas de Oxígeno , Neoplasias/tratamiento farmacológicoRESUMEN
The "anthracycline, Epirubicin (EPI)," in managing breast cancer, is highly cytotoxic. Tryptophan-derived 3-indolepropionic acid (3-IPA) decreases oxidative damage, and its prospect of alleviating EPI-induced cytotoxicity was examined in rats' hypothalamus-ovary-uterus axis. Female rats: Control, EPI (2.5 mg/kg), 3-IPA alone (40 mg/kg), EPI+3-IPA (2.5 mg/kg + 20 mg/kg), EPI + 3-IPA2 (2.5 mg/kg + 40 mg/kg) were treated for 28 days. Subsequently, reproductive hormones, oxidative and inflammatory stress biomarkers, and tissue histology were examined. 3-IPA prevented EPI-induced decreases in the follicle-stimulating hormone, estradiol, progesterone and prolactin levels. EPI-mediated reduction in antioxidant enzymes, reduced glutathione and total sulfhydryl groups were partially counteracted by 3-IPA co-treatment. Increased oxidative and inflammatory stress biomarkers caused by treatment with EPI alone were lessened by 3-IPA co-treatment. Also, 3-IPA reduced histological damage in the examined tissues. Conclusively, 3-IPA ameliorated biochemical markers and tissue injury caused by EPI treatment alone via an antioxidative and anti-inflammatory mechanism while stabilising serum hormone dynamics.
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Antioxidantes , Ovario , Femenino , Ratas , Animales , Ovario/patología , Epirrubicina/toxicidad , Epirrubicina/metabolismo , Ratas Wistar , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Oxidativo , Hormona Folículo Estimulante , Suplementos Dietéticos , Útero/metabolismo , Biomarcadores/metabolismoRESUMEN
Populations in malaria endemic areas are frequently exposed to mycotoxin-contaminated diets. The possible toxicological outcome of co-exposure to dietary aflatoxin B1 (AFB1) and artemisinin-based combination therapy warrants investigation to ascertain amplification or attenuation of cellular injury. Here, we investigated the neurobehavioral and biochemical responses associated with co-exposure to anti-malarial drug coartem, an artemether-lumefantrine combination (5 mg/kg body weight, twice a day and 3 days per week) and AFB1 (35 and 70 µg/kg body weight) in rats. Motor deficits, locomotor incompetence, and anxiogenic-like behavior induced by low AFB1 dose were significantly (p < 0.05) assuaged by coartem but failed to rescue these behavioral abnormalities in high AFB1-dosed group. Coartem administration did not alter exploratory deficits typified by reduced track plot densities and greater heat map intensity in high AFB1-dosed animals. Furthermore, the reduction in cerebral and cerebellar acetylcholinesterase activity, anti-oxidant enzyme activities, and glutathione and thiol levels were markedly assuaged by coartem administration in low AFB1 group but not in high AFB1-dosed animals. The significant attenuation of cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, xanthine oxidase activity, and lipid peroxidation by coartem administration was evident in low AFB1 group but not high AFB1 dose. Although coartem administration abated nitric oxide level, activities of myeloperoxidase, caspase-9, and caspase-3 in animals exposed to both doses of AFB1, these indices were significantly higher than the control. Coartem administration ameliorated histopathological and mophometrical changes due to low AFB1 exposure but not in high AFB1 exposure. In conclusion, contrary to AFB1 alone, behavioral and biochemical responses were not altered in animals singly exposed to coartem. Co-exposure to coartem and AFB1 elicited no additional risk but partially lessened neurotoxicity associated with AFB1 exposure.
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Antimaláricos , Artemisininas , Ratas , Animales , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Preparaciones Farmacéuticas/metabolismo , Antimaláricos/metabolismo , Antimaláricos/farmacología , Combinación Arteméter y Lumefantrina/metabolismo , Combinación Arteméter y Lumefantrina/farmacología , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/farmacología , Arteméter/metabolismo , Arteméter/farmacología , Estrés Oxidativo , Artemisininas/metabolismo , Artemisininas/farmacología , Peso Corporal , Hígado/metabolismoRESUMEN
OBJECTIVES: Diethylnitrosamine (DEN) is found in workplaces, processed meats, tobacco smoke, whiskey, etc. It is capable of forming DNA-adducts. Fluted pumpkin (Telfairia occidentalis [To]) is a medicinal plant, and its herbal preparations have been employed variously in ethnomedicine. Furthermore, it has been reported to possess anti-oxidant, anti-cancer, anti-inflammatory properties. We investigated the possible mitigating effect of the leaf paste of To on DEN-induced deleterious effects in male Wistar rats. METHODS: Forty-five rats weighing between 100 and 150 g were equally divided into nine groups and treated thus: Group 1 (negative control), Group 2 (0.05 mg/kg carboxymethyl cellulose [CMC] daily), Group 3 (positive control, 25 mg/kg bw DEN administered intraperitoneally thrice per week), Group 4 (25 mg/kg bw quercetin [QUE] daily alone), Groups 5 and 6 (100 and 200 mg/kg bw To daily, respectively), Group 7 (25 mg/kg bw DEN and QUE), Groups 8 and 9 (25 mg/kg bw DEN with 100 and 200 mg/kg bw To, respectively). Blood glucose levels, liver damage biomarkers (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyltransferase [γ-GT]), frequency of micronucleated polychromatic erythrocyte (mPCEs), and liver histology were assessed. RESULTS: DEN significantly (p<0.05) increased blood glucose levels, activities of ALT, AST and γ-GT, and frequency of mPCEs. Histologically, DEN caused a severe architectural anarchy. However, the intervention groups demonstrated the remarkable protective properties of To by ameliorating the adverse effects caused by DEN. CONCLUSIONS: Taken together, the leaf paste of To is capable of mitigating DEN-induced hepatotoxicity and clastogenicity in male Wistar rats.
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Furan and lead are contaminants of global concern due to the potential public health threat associated with their exposure. Herein, the neurobehavioral performance, biochemical effects and histological alterations associated with co-exposure to furan (8 mg/kg) and lead acetate at low, environmentally realistic concentrations (1, 10 and 100 µg PbAc/L) for 28 uninterrupted days were investigated in rats. The results demonstrated that locomotor, motor and exploratory deficits associated with separate exposure to furan and lead was exacerbated in the co-exposed rats. Furan and lead co-exposure aggravated the marked decrease in acetylcholinesterase activity and antioxidant status, elevation in oxido-inflammatory stress indices and caspases activation in the cerebrum and cerebellum of exposed rats compared with control. Furan and lead co-exposure worsened neuronal degeneration as verified by histomorphometry and histochemical staining. Collectively, furan and lead acts together to exacerbate neurotoxicity via inhibition of cholinergic system, induction of oxido-inflammatory stress and caspases activation in rats.
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Acetilcolinesterasa , Furanos , Ratas , Animales , Ratas Wistar , Acetilcolinesterasa/metabolismo , Oxidación-Reducción , Furanos/toxicidad , Caspasas , Estrés OxidativoRESUMEN
Despite lead widespread environmental pollution, its effect on humans and livestock's respiratory systems remains inadequately investigated. Similarly, furan is industrially relevant with enormous environmental presence. Lead and furan can be ingested -via lead pipes contaminated water and heat-treated food respectively. Thus, humans are inadvertently exposed continuously. Lead toxicity is well studied, and furan have earned a position on the IARC's list of carcinogens. Here, we evaluate the effect of co-exposure to lead and furan on rat lungs. Thirty Wistar rats were grouped randomly into six cohorts (n = 6) consisting of a control group, furan alone group, lead acetate (PbAc) alone group and three other groups co-exposure to graded PbAc (1, 10 & 100 µg/L) alongside a constant furan (8 mg/kg) dose. After twenty-eight days, enzymatic and non-enzymatic antioxidant, oxidative stress and inflammatory biomarkers were biochemically evaluated. The ELISA-based technique was used to measure oxidative-DNA damage (8-OHG), tumour protein 53 (TP53) expressed and tumour necrotic factor-alpha (TNF-α) level. Dose-dependent increases (p < 0.05) in reactive oxygen and nitrogen species, malondialdehyde, nitric oxide, myeloperoxidase, TNF-α and TP53 level, with an associated decrease (p < 0.05) in enzymatic and non-enzymatic antioxidants were observed in the furan, PbAc and the co-treated rats relative to the control. In addition, PbAc and furan treatment impaired the histoarchitectural structures of rat lungs, exemplified by pro-inflammatory cell infiltration and trafficking into the bronchioles and alveolar spaces. Co-exposure to furan and PbAc may contribute to lung dysfunction via loss of redox balance, genomic damage/instability, inflammation and disrupted histoarchitectural features.
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Plomo , Factor de Necrosis Tumoral alfa , Humanos , Ratas , Animales , Ratas Wistar , Plomo/toxicidad , Antioxidantes/farmacología , Estrés Oxidativo , Furanos/toxicidad , Acetatos/farmacología , PulmónRESUMEN
Aflatoxin B1 (AFB1) is known to derange the hepatorenal system by redox, DNA adduct formation and apoptotic networks. Endogenous 3-indole propionic acid (3-IPA) is a metabolite of tryptophan metabolism by gut microbiota that can protect against redox imbalance, inflammation and cellular lipid damage. We investigated the beneficial effect of 3-IPA against AFB1-mediated organ toxicity in male rats post 28 days of consecutive treatment. The 3-IPA (25 and 50 mg/kg) was orally administered alongside AFB1 (50 µg/kg) treatment. Biochemical and enzyme-linked immunosorbent assays were utilised to examine biomarkers of hepatorenal function, oxidative status and inflammation. DNA damage and apoptosis were also assessed, and histological staining techniques were used to investigate hepatorenal tissues for pathological indicators. The 3-IPA supplementation abated AFB1-mediated increases in biomarkers of hepatic and renal dysfunction in rat serum. Co-administration of 3-IPA further reduced AFB1-induced redox imbalance (by upregulating antioxidant mediators and enzymes [GSH, TSH, Trx, Trx-R, SOD, CAT, GPx and GST]; reducing reactive oxygen species, lipid peroxidation and DNA adduct [RONS, LPO and 8-OH-dG] formation; suppressing pro-inflammatory and apoptotic mediators [XO, MPO, NO, IL-1ß and Casp -9 and -3]; and upregulating the level of interleukin 10 (IL-10). Moreover, treatment with 3-IPA lessened hepatorenal tissue injuries. These findings suggest that augmenting 3-IPA endogenously from tryptophan metabolism may provide a novel strategy to forestall xenobiotics-mediated hepatorenal toxicity, including AFB1.
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Aflatoxina B1 , Aductos de ADN , Ratas , Animales , Masculino , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Aductos de ADN/metabolismo , Aductos de ADN/farmacología , Triptófano/metabolismo , Triptófano/farmacología , Glutatión/metabolismo , Hígado , Inflamación/metabolismo , Riñón/metabolismo , Biomarcadores/metabolismo , Estrés OxidativoRESUMEN
Aflatoxin B1 (AFB1) is a mycotoxin synthesised as a secondary metabolite by members of the Aspergillus species contaminating agricultural produce. Aspergillus species thrive in tropical climes, endemic to malaria. Artemisinin-based combination therapies (ACTs) effectively treat and prevent malaria recrudescence; Coartem (COA) is an ACT whose toxicity is evident. Although there are scanty studies on COA toxicity, the scientific literature is replete on AFB1 toxic effects -including carcinogenicity. The current research investigates AFB1 and COA toxicity in experimental Wistar rats' hepatorenal systems. Thirty albino rats were randomly grouped into five cohorts (n = 6) and treated as follows: Group I: Untreated control (2 mL/kg of corn oil); group II: AFB1 alone (70 µg/kg); group III: COA alone (5 mg/kg); group IV: COA and a low dose of AFB11 (5 mg/kg & 35 µg/kg); while Group V: COA and a high dose AFB12 (5 mg/kg & 70 µg/kg) by gavage. Our results show that exposure to AFB1 and COA significantly (p < 0.05) reduced superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities, besides reduced glutathione and total sulfhydryl groups level. Reactive oxygen and nitrogen species, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, nitric oxide, xanthine oxidase, and myeloperoxidase levels were increased (p < 0.05) in rats co-treated with COA and AFB1. Cell death was aggravated in COA and AFB1 groups, exemplified by increased Caspase-3 and 9 activities and alterations in the typical histological features of experimental rats' livers and kidneys. Finally, rats co-treated with AFB1 and COA experienced increased hepatorenal dysregulation, oxidative and inflammatory tissue damage, and apoptotic cell death. All the observed systemic perturbations occurred dose-dependently. It is crucial, therefore, to prevent AFB1 dietary contaminations during COA therapeutic regimen due to increased pathophysiological damage exerted on experimental rat liver and kidneys, as evidenced in this study.
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Aflatoxina B1 , Antioxidantes , Animales , Ratas , Antioxidantes/farmacología , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Combinación Arteméter y Lumefantrina/metabolismo , Combinación Arteméter y Lumefantrina/farmacología , Estrés Oxidativo , Ratas Wistar , Hígado , Apoptosis , Riñón/metabolismoRESUMEN
Lead (Pb) and furan are toxic agents, and persistent exposure may impair human and animal reproductive function. We therefore explored the effects of Pb and furan on male rat hypothalamic-pituitary-gonadal reproductive status, oxidative stress, inflammation, and genomic integrity. We found that co-exposure to Pb and furan reduced the activities of testicular function enzymes, endogenous antioxidant levels, total sulfhydryl group, and glutathione. Sperm abnormality, biomarkers of oxidative stress, inflammation, and p53 expression were increased in a dose-dependent manner by treatment with furan and Pb. Typical rat gonad histoarchitecture features were also damaged. Conclusively, co-exposure to Pb and furan induced male reproductive function derangement by decreasing the antioxidant defences in rats, increasing abnormalities in spermatozoa morphology, and reducing reproductive hormone in circulation. These pathophysiological alterations, if persistent, might provide a permissive environment for potentiating reproductive dysfunction and infertility.
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Inadvertent exposure to furan and Pb is associated with hepatorenal abnormalities in humans and animals. It is perceived that these two chemical species may work in synergy to orchestrate liver and kidney damage. Against this background, we investigated the combined effect of furan and incremental lead (Pb) exposure on hepatorenal dysfunction. Wistar rats (n = 30; 150 g) were treated for 28 days accordingly: Control; FUR (8 mg/kg), PbAc (100 µg/L), FUR + PbAc1 (8 mg/kg FUR + 1 µg/L PbAc); FUR + PbAc1 (8 mg/kg FUR + 10 µg/L PbAc), and FUR + PbAc1 (8 mg/kg FUR + 100 µg/L PbAc). Biomarkers of hepatorenal function, oxidative stress, inflammation, DNA damage, and apoptosis were examined. Furan and incrementally Pb exposure increased the levels of hepatorenal biomarkers and oxidative and pro-inflammatory mediators, including lipid peroxidation, reactive oxygen and nitrogen species, and interleukin-1 beta. Increased DNA damage, caspases- 9 and -3, and atypical histoarchitecture of the hepatorenal tissues exemplified furan and Pb treatment-related perturbations. Furthermore, the levels of antioxidants and IL-10 were also suppressed. Furan and Pb dose-dependently exacerbated hepatorenal derangements by altering the redox and inflammatory rheostats, worsened DNA damage, and related apoptotic onset that may potentiate hepatorenal disorders in humans and animals. The findings validate the synergistic effect of furan and Pb in the pathophysiology of kidney and liver disorders.
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Antioxidantes , Interleucina-10 , Animales , Antioxidantes/farmacología , Caspasas/farmacología , Furanos/toxicidad , Humanos , Mediadores de Inflamación , Interleucina-10/farmacología , Interleucina-1beta , Plomo/toxicidad , Hígado , Nitrógeno/farmacología , Oxidación-Reducción , Estrés Oxidativo , Oxígeno/farmacología , Ratas , Ratas Wistar , AguaRESUMEN
Rheumatoid arthritis (RA) is a debilitating disease associated with locomotion impairment, and conventional therapeutic drugs are not optimal for managing RA. There is an avalanche of medications used for the management of RA. Still, studies have shown that they are associated with severe side effects, including hepatotoxicity, retinopathy, and cardiotoxicity disorders of the central nervous system (CNS), skin, blood, and infections. Complementary and alternative medicine (CAM) is currently gaining attention as a novel panacea for managing debilitating diseases, such as RA. Nigerian folk herbal remedies are replete with a plethora of curative medicine, albeit unvalidated scientifically but with seemingly miraculous provenance. Studies of the identification of bioactive compounds present in these botanicals using advanced spectral analytical techniques have enhanced our understanding of the role of Nigerian herbal remedies in the treatment and management of RA. Interestingly, experimental studies abound that the bioactive compounds present in the extracts of plant botanicals protected animals from the development of RA in different experimental models and reduced the toxicity associated with conventional therapeutics. Validated mechanisms of RA amelioration in human and animal models include suppression of the expression of NF-κB, IL-1ß, TNF-α, IL-6, IL-8, IL-17, IL-23, chemokines, TGF-ß, RANKL, RANK, iNOS, arginase, COX-2, VEGFA, VEGFR, NFATC1, and TRAP in the synoviocytes. Decreased ROS, NO, MDA, carbonyl groups, and PGE2 in the synovial fluid increased the expression of PPARα/γ; antioxidant and anti-inflammatory molecules also improve RA etiology. In this mini-review, we discuss the global burden of RA, the novel role of plant-based botanicals as potential therapeutics against signaling pathways in RA. Also addressed is the possible repurposing/reprofiling of plant botanicals to increase their therapeutic index among RA patients that patronize traditional healers in Nigeria with a global projection.
Asunto(s)
Artritis Reumatoide , Sinoviocitos , Animales , Artritis Reumatoide/tratamiento farmacológico , Fibroblastos/metabolismo , Humanos , FN-kappa B/metabolismo , Nigeria , Sinoviocitos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We examined the protective effect of the apigeninidin (API)-enriched fraction from Sorghum bicolor sheaths extracts (SBE-05, SBE-06, and SBE-07) against aflatoxin B1 (AFB1)-induced dysregulation of male rat's reproductive system that may trigger infertility. Male rats (160 ± 12 g) were treated with AFB1 (50 µg/kg) along with 5 or 10 mg/kg of SBE-05, SBE-06, and SBE-07 for 28 days. Subsequently, we assessed the reproductive hormone-prolactin, FSH, LH, testosterone levels, and testicular function enzymes. Moreover, we examined rats' testes, epididymis, and hypothalamus for oxidative and inflammatory stress biomarkers, caspase-9 activity and tissues pathology. We observed that comparative to AFB1 alone treated rats, API co-treatment significantly (p < 0.05) abated the AFB1-mediated decrease in prolactin and antioxidant defenses and lessened lipid peroxidation (LPO) and reactive oxygen and nitrogen species levels in the examined organs-testes, epididymis, and hypothalamus. API abated AFB1-induced hormone decreases-testosterone, FSH, and LH; and caused improvement in sperm quantity and quality. API lessened AFB1-mediated increase in pro-inflammatory cytokine, increased interleukin-10 level, an anti-inflammatory cytokine and reduced caspase-9 activities. In addition, API reduced alterations in the examined tissue histology. Our findings suggest that S. bicolor API-enrich extracts have active antioxidative, antiapoptotic, and anti-inflammatory activities, which can protect against AFB1-induced dysfunction of the hypothalamic-pituitary-gonadal axis.
Asunto(s)
Aflatoxina B1 , Antocianinas , Apigenina , Sorghum , Aflatoxina B1/toxicidad , Animales , Antocianinas/farmacología , Antioxidantes/farmacología , Apigenina/farmacología , Caspasa 9 , Citocinas/metabolismo , Hormona Folículo Estimulante , Hipotálamo/metabolismo , Masculino , Estrés Oxidativo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Prolactina , Ratas , Sorghum/química , TestosteronaRESUMEN
The application of chlorpyrifos (CPF), an organophosphorus pesticide to control insects, is associated with oxidative stress and reduced quality of life in humans and animals. Indole-3-propionic acid (IPA) is a by-product of tryptophan metabolism with high antioxidant capacity and has the potential to curb CPF-mediated toxicities in the hepatorenal system of rats. It is against this background that we explored the subacute exposure of CPF and the effect of IPA in the liver and kidney of thirty rats using five cohort experimental designs (n = 6) consisting of control (corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), IPA alone (50 mg/kg), CPF + IPA1 (5 mg/kg + 25 mg/kg), and CPF + IPA2 (5 mg/kg + 50 mg/kg). Subsequently, we evaluated biomarkers of hepatorenal damage, oxidative and nitrosative stress, inflammation, DNA damage, and apoptosis by spectrophotometric and enzyme-linked immunosorbent assay methods. Our results showed that co-treatment with IPA decreased CPF-upregulated serum hepatic transaminases, creatinine, and urea; reversed CPF downregulation of SOD, CAT, GPx, GST, GSH, Trx, TRx-R, and TSH; and abated CPF upregulation of XO, MPO, RONS, and LPO. Co-treatment with IPA decreased CPF-upregulated IL-1ß and 8-OHdG levels, caspase-9 and caspase-3 activities, and increased IL-10. In addition, IPA averts CPF-induced histological changes in the liver and kidney of rats. Our results demonstrate that co-dosing CPF-exposed rats with IPA can significantly decrease CPF-induced oxidative stress, pro-inflammatory responses, DNA damage, and subsequent pro-apoptotic responses in rats' liver and kidneys. Therefore, supplementing tryptophan-derived endogenous IPA from exogenous sources may help avert toxicity occasioned by inadvertent exposure to harmful chemicals, including CPF-induced systemic perturbation of liver and kidney function.
Asunto(s)
Cloropirifos , Insecticidas , Plaguicidas , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Biomarcadores/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Caspasa 9/farmacología , Cloropirifos/metabolismo , Aceite de Maíz/metabolismo , Aceite de Maíz/farmacología , Creatinina/metabolismo , Daño del ADN , Humanos , Indoles/metabolismo , Insecticidas/farmacología , Interleucina-10/metabolismo , Hígado , Compuestos Organofosforados/metabolismo , Plaguicidas/metabolismo , Propionatos , Calidad de Vida , Ratas , Superóxido Dismutasa/metabolismo , Tirotropina , Transaminasas/metabolismo , Transaminasas/farmacología , Triptófano , Urea/metabolismoRESUMEN
Sorghum bicolor plant has a high abundance of 3-deoxyanthocyanins, flavonoids and other polyphenol compounds that have been shown to offer numerous health benefits. Epidemiological studies have linked increased intake of S. bicolor to reduced risk of certain cancer types, including lung adenocarcinoma. S. bicolor extracts have shown beneficial effects in managing hepatorenal injuries. This study investigated the cytotoxic potential of three apigeninidin-rich extracts of S. bicolor (SBE-05, SBE-06 and SBE-07) against selected cancer cell lines and their ameliorative effect on aflatoxin B1 (AFB1)-mediated hepatorenal derangements in rats. We observed that, among the three potent extracts, SBE-06 more potently and selectively suppressed the growth of lung adenocarcinoma cell line (A549) (IC50 = 6.5 µg/mL). SBE-06 suppressed the expression of STAT3 but increased the expression of caspase 3. In addition, SBE-05, SBE-06 and SBE-07 inhibited oxidative and nitrosative stress, inflammation, and apoptosis and preserved the histoarchitectural networks of the liver and kidney of rats treated with AFB1. These in vitro and in vivo studies indicate the potential of these cheap and readily accessible extracts for cancer therapy and as chemo-preventive agents in preventing aflatoxin-related health issues.